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Due to its unique strain-light response, non-contact measurement and visualization characteristics, strain-sensitive mechanoluminescent (ML) materials are expected to replace traditional strain gauges as a new generation of strain sensing materials. The strain sensing technology has high requirements for the multi-parameter response characteristics, stability and sensing working range of sensing materials. In this work, a composite flexible strain sensing ML device composed of La 4 GeO 8 doped with lanthanide rare earth ions Ln3+ and polydimethylsiloxane (PDMS) is proposed. The ML of the device can produce good linear response to stress, strain and loading rate under tensile action. The minimum strain response threshold is less than 2% of the relative strain, and the sensing range can reach 100% of the relative strain in the full elastic deformation range. In addition, the ML intensity of La 4 GeO 8 : Ln3+@PDMS has the characteristic of self-recovery, and its self-recovery is related to the maximum strain of loading and the placing time. The wavelength (visible-near infrared) and color adjustable ML can be achieved by adjusting the type and doping concentration of rare earth ions. Moreover, the device has high thermal stability and water resistance, indicating that it is also adaptable to extremely harsh environments. The results show that La 4 GeO 8 : Ln3+@PDMS can be used as a strain-sensing-material with multi-dimensional mechanical parameter response, and has potential application prospects in the field of flexible tensile strain sensors. [ABSTRACT FROM AUTHOR]

Background: Otitis externa is a commonly diagnosed dermatological disorder in canines. The pathogens primarily involved in canine otitis externa (COE) include Staphylococcus pseudintermedius, Pseudomonas aeruginosa, Proteus mirabilis, and Malassezia pachydermatis. As COE tends to be superficial, medications delivered topically are often effective and practical in managing the condition. As such, there is a wide variety of approved topical products currently available in the market. The efficacy of topical dosage forms can be dependent on various factors such as the pharmacology of active constituents and the physicochemical properties of the formulation, including pH, viscosity, spreadability, and bio-adhesion. Currently, there is a lack of published literature available on the optimal properties of topical COE products. In this study, we compared the physicochemical properties of nine commercially available otic veterinarian products in Australia used clinically to manage COE. Results: Based on our comparative analysis, the pH (6.26 ± 0.04) of an aqueous-based product was similar to a healthy dog's external auditory canal. Products containing polymers exhibited higher viscosity and bio-adhesion. Spreadability was inversely related to viscosity and Osurnia ® a product with high viscosity demonstrated the lowest spreadability. Aqueous-based otic products showed better syringebility whereas oil-based systems required higher force to expel the products. Variability in droplet size was noted. Derm Otic, Baytril Otic, and Aurizon Ear Drops had the lower standard deviation which indicates they would give a more consistent dose. Conclusions: Findings from this work provide considerations for industry researchers or formulation scientists working in the area of otic dosage formulations. [ABSTRACT FROM AUTHOR]

While the global market for veterinary products has been expanding rapidly, there is still a lack of specialist knowledge of equine pharmaceutics. In many cases, the basic structure of the gastrointestinal tract (GIT) and integumentary system of the horse shares similarities with those of humans. Generally, the dosage form developed for humans can be repurposed to deliver equine medications; however, due to physiological variation, the therapeutic outcomes can be unpredictable. This is an area that requires more research, as there is a clear deficiency in literature precedence on drug delivery specifically for horses. Through a careful evaluation of equine anatomy and physiology, novel drug delivery systems (NDDSs) can be developed to adequately address many of the medical ailments of the horse. In addition to this, there are key considerations when delivering oral, topical, and parenteral drugs to horses, deriving from age and species variation. More importantly, NDDSs can enhance the duration of action of active drugs in animals, significantly improving owner compliance; and ultimately, enhancing the convenience of product administration. To address the knowledge gap in equine pharmaceutical formulations, this paper begins with a summary of the anatomy and physiology of the equine gastrointestinal, integumentary, and circulatory systems. A detailed discussion of potential dosage-form related issues affecting horses, and how they can be overcome by employing NDDSs is presented. [ABSTRACT FROM AUTHOR]

Strategies that alter the pH of wounds to improve healing outcomes are an emerging area of interest. Currently, there is limited understanding of the effect of hydrogen (H+) on the functionality of skin cells during proliferation and migration, highlighting the need for research to determine the effect of pH during wound healing. This study aimed to determine the effect of acidification on the metabolic activity and migration of human immortalized keratinocytes (HaCaT) and human foreskin fibroblasts (HFF). In vitro models were used with phosphoric and citric acid buffers at a pH range between 3 and 7. Our results showed that cells were more viable in buffers with low rather than high ionic strength. A time-dependent effect of the acidification treatment was also observed with cell metabolic activity varying with treatment duration and frequency. Our results showed that a 24 h treatment and subsequent resting phase significantly improved cell proliferation and migration. This in vitro study is the first to establish a correlation between the role of acidic pH, molarity and treatment regimen in cellular activity. Our data demonstrated a positive effect of acidic pH on cell metabolic activity and migration rate, suggesting a clinical potential in indications such as wound healing. [ABSTRACT FROM AUTHOR]

Aims: To examine the physical, chemical and microbiological stability characteristics of an extemporaneously compounded carbimazole 2 mg/mL oral suspension. Methods and Results: To determine the chemical stability of carbimazole in oral suspension, an analytical method was developed with high‐performance liquid chromatography (HPLC) that achieved a good resolution of the analysis. The physical and chemical stability studies of the drug were conducted at four different storage conditions: 4°C, 25°C, 4°C in‐use (to simulate a patient daily use condition), and 7 days at 4°C and 3 days at 25°C (to simulate a condition in which a patient does not return the medication back into the refrigerator after use). The microbiological test was performed on the "4°C in‐use" storage condition. The preparations were found to be physically and microbiologically stable since there were no significant changes in colour, odour, dispersion and microbial contamination tests. Regarding chemical stability, samples stored at 4°C and 25°C maintained more than 90% drug recovery limit for up to 3 weeks and 3 days, respectively. There were no significant changes in pH value for up to 6 weeks. Conclusion: A shelf life of up to 19 days at 4°C, based on the 95% lower confidence interval (CI) of the data obtained, and 2 days at room temperature can be recommended for carbimazole oral suspension. [ABSTRACT FROM AUTHOR]

[Display omitted] Applying the advanced CALYPSO structure searching method and first principles calculations, we predict a novel superhard structure for Ti 2 B 5 , which belongs to the monoclinic C 2/ m space group. The previously known Hf 2 B 5 , W 2 B 5 , and δ -V 2 O 5 -type structures are also selected as the potential structures for Ti 2 B 5. It is shown that the predicted C 2/ m structure is the most stable phase among these considered structures within the range of 0-100GPa. The calculations of the phonon dispersion and elastic constants affirm that the predicted C 2/ m phase is dynamically and mechanically stable. The predicted high shear modulus (249 GPa) and large hardness (46.9 GPa) show that it should be an underlying superhard material. In addition, the elastic anisotropy of Ti 2 B 5 is also explored by investigating the directional dependence of the Young's modulus, shear modulus, and Poisson's ratio as well as some well anisotropy indices. The particular analyses of the density of states and electron charge density distribution verify that the strong B-B and Ti-B covalent bonds in the predicted C 2/ m- Ti 2 B 5 phase play an important part in its hardness and structural stability. [ABSTRACT FROM AUTHOR]

Non-melanoma skin cancer (NMSC) is the most prevalent malignancy worldwide, with approximately 6.3 million new cases worldwide in 2019. One of the key management strategies for NMSC is a topical treatment usually utilised for localised and early-stage disease owing to its non-invasive nature. However, the efficacy of topical agents is often hindered by poor drug penetration and patient adherence. Therefore, various research groups have employed advanced drug delivery systems, including topical patches to overcome the problem of conventional topical treatments. This review begins with an overview of NMSC as well as the current landscape of topical treatments for NMSC, specifically focusing on the emerging technology of topical patches. A detailed discussion of their potential to overcome the limitations of existing therapies will then follow. Most importantly, to the best of our knowledge, this work unprecedentedly combines and discusses all the current advancements in innovative topical patches for the treatment of NMSC. In addition to this, the authors present our insights into the key considerations and emerging trends in the construction of these advanced topical patches. This review is meant for researchers and clinicians to consider utilising advanced topical patch systems in research and clinical trials toward localised interventions of NMSC. [ABSTRACT FROM AUTHOR]

Purpose. Results of a study to determine the stability of an extemporaneously compounded minoxidil oral suspension under various temperature and stress conditions are reported. Methods. Commercially available minoxidil tablets (10 mg) were crushed to a fine powder, and predetermined amounts of 2 suspending vehicles were added to produce a 1-mg/mL suspension, which was stored in glass bottles at room temperature (25 ± 2 °C) or in a refrigerator (4 ± 2 °C). To simulate daily patient use, 5 days weekly 1 bottle of the suspension was removed from refrigerated storage and shaken and 0.5 mL of the contents discarded. At each specified time point, samples were analyzed in duplicate (n = 6 for each test condition) using a validated high-performance liquid chromatography method. Samples were visually observed and their pH measured at each time point. Microbiological studies were performed on day 0 and at week 24. Results. The mean percentage of initial minoxidil concentration remaining in all refrigerated samples exceeded 90% throughout the 24-week study, with no change in appearance, pH, microbial activity, odor, or redispersibility. During storage at room temperature, the suspension exhibited a color change at week 4, with slight sedimentation after 6 weeks, although minoxidil recovery exceeded 90% for 10 weeks. Conclusion. An extemporaneously compounded minoxidil oral suspension was stable for 24 weeks when stored in a refrigerator. This suspension can be used for up to 3 weeks when stored at room temperature. [ABSTRACT FROM AUTHOR]

The transdermal delivery of 2 fluorescent probes with similar molecular weight but different lipophilicity, into and through the skin from 2 commercially available transdermal bases, pluronic lecithin organogel, and Lipoderm ® has been evaluated. First, in vitro penetration of fluorescein sodium and fluorescein (free acid) through porcine skin was evaluated. Retention and depth distribution profiles in skin were obtained by tape stripping and then followed by optical sectioning using multiphoton microscopy. The results showed that Lipoderm ® led to an enhanced penetration of the hydrophilic compound, fluorescein sodium. For the lipophilic compound fluorescein (free acid), Lipoderm ® performed similar to pluronic lecithin organogel base, where minimal drug was detected in either receptor phase. The skin retention and depth distribution results also showed that the hydrophilic fluorescein sodium had high skin retention with Lipoderm ® , whereas fluorescein (free acid) had very low penetration and retention with increasing skin depth. Moreover, optical sectioning by multiphoton microscopy revealed an uneven distribution of probes across the skin in the x-y plane for both transdermal bases. This work showed that a hydrophilic compound has significantly increased skin penetration and retention when formulated with Lipoderm ® , and the skin retention of the probe was the main determinant of its skin flux. [ABSTRACT FROM AUTHOR]

Background: Otitis externa is a commonly diagnosed dermatological disorder in canines. The pathogens primarily involved in canine otitis externa (COE) include Staphylococcus pseudintermedius, Pseudomonas aeruginosa, Proteus mirabilis, and Malassezia pachydermatis. As COE tends to be superficial, medications delivered topically are often effective and practical in managing the condition. As such, there is a wide variety of approved topical products currently available in the market. The efficacy of topical dosage forms can be dependent on various factors such as the pharmacology of active constituents and the physicochemical properties of the formulation, including pH, viscosity, spreadability, and bio-adhesion. Currently, there is a lack of published literature available on the optimal properties of topical COE products. In this study, we compared the physicochemical properties of nine commercially available otic veterinarian products in Australia used clinically to manage COE. Results: Based on our comparative analysis, the pH (6.26 ± 0.04) of an aqueous-based product was similar to a healthy dog's external auditory canal. Products containing polymers exhibited higher viscosity and bio-adhesion. Spreadability was inversely related to viscosity and Osurnia ® a product with high viscosity demonstrated the lowest spreadability. Aqueous-based otic products showed better syringebility whereas oil-based systems required higher force to expel the products. Variability in droplet size was noted. Derm Otic, Baytril Otic, and Aurizon Ear Drops had the lower standard deviation which indicates they would give a more consistent dose. Conclusions: Findings from this work provide considerations for industry researchers or formulation scientists working in the area of otic dosage formulations. [ABSTRACT FROM AUTHOR]

The present review discusses the pharmaceutical impact of the anatomy and physiology of the canine gastrointestinal tract to provide a comprehensive guide to the theories and challenges associated with the development of oral drug delivery systems for dogs. Novel pharmaceutical technologies applied to veterinary drugs are discussed indicating the advantages and benefits for animals. There are currently immense research and development efforts being funneled into novel canine health products. Such products are being used to overcome limitations of drugs that display site-dependent absorption or possess poor biopharmaceutical properties. Techniques that are employed to increase bioavailability of the Biopharmaceutics Classification System class II drugs are discussed in this article. Furthermore, an overview of palatable oral formulations for dog care is provided as an approach to easy administration. In vitro and in vivo evaluation and correlation of oral drug formulations in dogs are also addressed. This article assesses the outlook of canine oral drug development recognizing substantial growth forecasts of the dog care market. [ABSTRACT FROM AUTHOR]

Simple Summary: Optimum fertility requires the deposition of sperm at the appropriate time relative to ovulation, which can be achieved by using gonadotrophin-releasing hormone (GnRH) to control the time of ovulation. Following insemination, the establishment and maintenance of pregnancy and embryo survival are promoted by progesterone released from the ovarian corpora lutea, also under the control of GnRH-stimulated gonadotrophin release. This review examines the effect of the application of GnRH on the productivity and fertility of food-producing animals. Over several decades, exogenous GnRH and agonists have been employed for controlling reproductive cascades in animals, and treating some reproductive morbidities. The administration of GnRH is used in animals to counter ovarian dysfunction, induce ovulation, and to increase conception and pregnancy rates. GnRH and its agonists are used in the treatment of cystic ovarian degeneration and repeat breeder syndrome. The development of protocols for GnRH administration by intramuscular injection, intramuscular or subcutaneous implants, and intravaginal deposition has empowered their clinical use worldwide. Currently, exogenous GnRH products are a central part of several pre- and post-breeding programs for the enhancement of fertility, including the control of estrous cycles and timing of ovulation, development of fixed-time artificial insemination protocols, improved embryo survival, and the treatment of reproductive morbidity. The aim of the present review is to summarize the application of exogenous GnRH agonists in food animal production. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) has significantly affected a large proportion of the elderly population worldwide. According to the World Health Organization, approximately 8.5 million people worldwide are living with PD. In the United States, an estimated one million people are living with PD, with approximately 60,000 new cases diagnosed every year. Conventional therapies available for Parkinson's disease are associated with limitations such as the wearing-off effect, on-off period, episodes of motor freezing, and dyskinesia. In this review, a comprehensive overview of the latest advances in DDSs used to reduce the limitations of current therapies will be presented, and both their promising features and drawbacks will be discussed. We are also particularly interested in the technical properties, mechanism, and release patterns of incorporated drugs, as well as nanoscale delivery strategies to overcome the blood–brain barrier. [ABSTRACT FROM AUTHOR]

There has been little understanding of acidification functionality in wound healing, highlighting the need to study the efficacy of wound acidification on wound closure and cellular activity in non-infected wounds. This study is focused on establishing the healing potential of wound acidification in non-infected wounds. Acidic buffers, constituting either phosphoric or citric acid, were employed to modify the physiological pH of non-infected full-thickness excisional murine wounds. Acidification of the wound by acidic buffers was found to be an effective strategy to improve wound healing. A significant improvement in wound healing parameters was observed as early as 2 days post-treatment with acidic buffers compared to controls, with faster rate of epithelialization, wound closure and higher levels of collagen at day 7. pH is shown to play a role in mediating the rate of wound healing, with acidic buffers formulated at pH 4 observed to stimulate faster recovery of wounded tissues than pH 6 buffers. Our study shows the importance of maintaining an acidic wound microenvironment at pH 4, which could be a potential therapeutic strategy for wound management. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to assess the potential of a novel delivery device for administering drugs that suffer from a high degree of first-pass metabolism. Methods A tri-layered buccal mucoadhesive patch, comprising a medicated dry tablet adhered to a mucoadhesive film, was prepared and characterized by its physicochemical properties and mucoadhesive strength. Nicotine was used as a model drug for the characterization of drug release and drug permeation. The influence of different adsorbents on the release of nicotine base from the patches was evaluated in vitro. Different molecular forms of nicotine (base and complex salt) were evaluated for their effect on release performance and permeation in vitro. Key findings Results demonstrated acceptable physicochemical and mucoadhesive properties for the tri-layered patch. Rapid release of nicotine was observed when nicotine base was incorporated with calcium sulfate dihydrate as the adsorbent. Patches incorporating nicotine base showed distinct advantages over those containing nicotine polacrilex, in terms of drug release (complete drug release achieved at 30 vs 60 min) and transmucosal permeation (37.28 ± 4.25 vs 2.87 ± 0.26% of the dose permeating through mucosa within 120 min). Conclusions The novel tri-layered patch can effectively adhere to, and deliver an active ingredient through the buccal mucosa, confirming its potential for buccal mucoadhesive drug delivery. [ABSTRACT FROM AUTHOR]

A novel drug delivery system preventing Glioblastoma multiforme (GBM) recurrence after resection surgery is imperatively required to overcome the mechanical limitation of the current local drug delivery system and to offer personalised treatment options for GBM patients. In this study, 3D printed biodegradable flexible porous scaffolds were developed via Fused Deposition Modelling (FDM) three-dimensional (3D) printing technology for the local delivery of curcumin. The flexible porous scaffolds were 3D printed with various geometries containing 1, 3, 5, and 7% (w/w) of curcumin, respectively, using curcumin-loaded polycaprolactone (PCL) filaments. The scaffolds were characterised by a series of characterisation studies and in vitro studies were also performed including drug release study, scaffold degradation study, and cytotoxicity study. The curcumin-loaded PCL scaffolds displayed versatile spatiotemporal characteristics. The polymeric scaffolds obtained great mechanical flexibility with a low tensile modulus of less than 2 MPa, and 4 to 7-fold ultimate tensile strain, which can avoid the mechanical mismatch problem of commercially available GLIADEL wafer with a further improvement in surgical margin coverage. In vitro release profiles have demonstrated the sustained release patterns of curcumin with adjustable release amounts and durations up to 77 h. MTT study has demonstrated the great cytotoxic effect of curcumin-loaded scaffolds against the U87 human GBM cell line. Therefore, 3D printed curcumin-loaded scaffold has great promise to provide better GBM treatment options with its mechanical flexibility and customisability to match individual needs, preventing post-surgery GBM recurrence and eventually prolonging the life expectancy of GBM patients. [ABSTRACT FROM AUTHOR]

The age-related loss of circulating estrogen that occurs during the menopausal transition manifests itself through a variety of symptoms including vasomotor (hot flushes and night sweats), genito-urinary syndrome (vaginal dryness and urinary symptoms), sexual dysfunction, mood, and sleep disturbance that often last longer than a decade. Furthermore, reductions in estrogen level increase the risks of chronic complications such as osteoporosis, cardiovascular disease, and cognitive decline among others, thereby affecting the quality of life of women. Although oral estrogens are the most widely used therapy for menopausal symptoms, they suffer from poor bioavailability, and there are concerns over their safety, creating a significant concern to consumers. Mucoadhesive buccal films are an innovative dosage form that offers several advantages including avoidance of the first-pass metabolism, fast onset of action, and importantly, improved patient acceptance. In the current work, we developed mucoadhesive estradiol film for hormonal replacement therapy using film-forming polymers. Two approaches, namely, co-solvency and nano-emulsion were evaluated to increase solubility and hence incorporate estradiol, a poorly water-soluble drug, into a formulation made from the hydrophilic polymer/s. The films were characterised for their mechanical and physicochemical properties. In-vitro release study showed that about 80% of the drug was released within 6 min from films prepared by the nano-emulsion approach, whereas it took about 10.5 min to get similar drug release from films prepared by the co-solvency approach. The ex-vivo permeation result indicates that about 15% of the drug permeated across the porcine buccal mucosa in the first 10 h from films prepared by the nano-emulsion approach, while permeation across porcine buccal mucosa was only observed at around 24 h from films prepared by the co-solvency method. The nano-emulsion films were evaluated for in vivo performance using a convolution technique using R software. The predicted Cmax and Tmax were found to be 740.74 ng mL−1 and 7 min, respectively, which were higher than previously reported in vivo concentration from oral tablets. The results demonstrated that mucoadhesive film of estradiol based on the nano-emulsion approach could be a promising platform for the delivery of estradiol through the buccal mucosa for the treatment of menopausal symptoms. [ABSTRACT FROM AUTHOR]

Delta inulin, also known as microparticulate inulin (MPI), was modified by covalently attaching doxorubicin to its nanostructured surface for use as a targeted drug delivery vehicle. MPI is readily endocytosed by monocytes, macrophages, and dendritic cells and in this study, we sought to utilize this property to develop a system to target anti-cancer drugs to lymphoid organs. We investigated, therefore, whether MPI could be used as a vehicle to deliver doxorubicin selectively, thereby reducing the toxicity of this antibiotic anthracycline drug. Doxorubicin was covalently attached to the surface of MPI using an acid–labile linkage to enable pH-controlled release. The MPI-doxorubicin conjugate was characterized using FTIR and SEM, confirming covalent attachment and indicating doxorubicin coupling had no obvious impact on the physical nanostructure, integrity, and cellular uptake of the MPI particles. To simulate the stability of the MPI-doxorubicin in vivo, it was stored in artificial lysosomal fluid (ALF, pH 4.5). Although the MPI-doxorubicin particles were still visible after 165 days in ALF, 53% of glycosidic bonds in the inulin particles were hydrolyzed within 12 days in ALF, reflected by the release of free glucose into solution. By contrast, the fructosidic bonds were much more stable. Drug release studies of the MPI-doxorubicin in vitro, demonstrated a successful pH-dependent controlled release effect. Confocal laser scanning microscopy studies and flow cytometric analysis confirmed that when incubated with live cells, MPI-doxorubicin was efficiently internalized by immune cells. An assay of cell metabolic activity demonstrated that the MPI carrier alone had no toxic effects on RAW 264.7 murine monocyte/macrophage-like cells, but exhibited anti-cancer effects against HCT116 human colon cancer cells. MPI-doxorubicin had a greater anti-cancer cell effect than free doxorubicin, particularly when at lower concentrations, suggesting a drug-sparing effect. This study establishes that MPI can be successfully modified with doxorubicin for chemotherapeutic drug delivery. [ABSTRACT FROM AUTHOR]

5-fluorouracil (5-FU), commercially available as a topical product, is approved for non-melanoma skin cancer (NMSC) treatment with several clinical limitations. This work aimed to develop 5-FU-loaded topical patches as a potential alternative to overcome such drawbacks. The patches offer accurate dosing, controlled drug release and improved patient compliance. Our study highlights the development of Eudragit® E (EuE)-based drug-in-adhesive (DIA) patches containing a clinically significant high level of 5-FU (approximately 450 µg/cm2) formulated with various chemical permeation enhancers. The patches containing Transcutol® (Patch-TRAN) or oleic acid (Patch-OA) demonstrated significantly higher skin penetration ex vivo than their control counterpart, reaching 5-FU concentrations of 76.39 ± 27.7 µg/cm2 and 82.56 ± 8.2 µg/cm2, respectively. Furthermore, the findings from in vitro permeation studies also validated the superior skin permeation of 5-FU achieved by Patch-OA and Patch-TRAN over 72 h. Moreover, the EuE-based DIA patch platform demonstrated suitable adhesive and mechanical properties with an excellent safety profile evaluated through an inaugural in vivo human study involving 11 healthy volunteers. In conclusion, the DIA patches could be a novel alternative option for NMSC as the patches effectively deliver 5-FU into the dermis layer and receptor compartment ex vivo for an extended period with excellent mechanical and safety profiles. [ABSTRACT FROM AUTHOR]

Abstract Smart hydrogels with pH and enzyme triggered release suitable for colon specific drug delivery were prepared by crosslinking inulin with pyromellitic dianhydride (PMDA) in a simple one pot synthesis. Back titration, Fourier transform infrared spectroscopy (FTIR) and ultraviolet spectrophotometry (UV) demonstrated that the hydrogel crosslinking reaction resulted in ester linkages and carboxylic acid groups and that the amount of the crosslinker in the hydrogel increased with increasing PMDA concentration in the crosslinking reaction. Thermal analysis and scanning electron microscopy (SEM) confirmed the chemical change by illustrating the hydrogels changed thermal properties and appearance compared to inulin. This hydrogel showed excellent swelling in water and the degree of swelling was inversely proportional to the cross-linking density, as determined using Flory-Rehner theory. Due to the presence of the carboxylic acid groups in the structure, the swelling was pH dependent, with significantly reduced swelling as acidity decreased from pH 7.4 to pH 1.2. Highlights • Novel hydrogel was obtained by esterification reaction between inulin and PMDA • The synthesized hydrogel were characterized using different analytical techniques and swelling experiment • By varying the ratio of PMDA, hydrogels with different crosslink density can be obtained • Hydrogels demonstrated pH dependent swelling [ABSTRACT FROM AUTHOR]

There is increasing interest to administer ibuprofen as a continuous infusion instead of a traditional bolus for treating Patent Ductus Arteriosus (PDA). However, its compatibility data with commonly used drugs in the neonatal period, including parenteral nutrition (PN) and lipids is unavailable. The aim is to determine the compatibility of intravenous ibuprofen lysine with various ANZNN parenteral nutrition consensus group standard neonatal PN formulations and lipids. The PN and lipid solutions used in a tertiary neonatal unit were obtained. These included a Starter, Standard Preterm and low carbohydrate PN, and IV SMOF lipid admixture (SMOFLipid 20% 15 mL; Vitalipid N infant 4 mL, Soluvit N 1 mL) plus vitamin mixtures. 10% glucose was used as a control. 1:1 mixtures of different concentrations (1.25 to 5mg/mL) of ibuprofen lysine and each of the PN/glucose/lipid formulations were made. Samples were taken at hourly intervals for a total of 4 hours and tested for both physical (visual assessment, pH and microscopy) and chemical compatibility (High Performance Liquid Chromatography analysis). Zeta potential and particle diameter were measured for SMOF lipid admixture and ibuprofen combination to assess emulsion stability. 24 hour stability of ibuprofen dilution in 5 mL BD Luer-lok polypropylene syringes at 25°C was also assessed. Most PN formed opaque solutions when mixed with ibuprofen 2.5 and 5mg/mL solutions. However, ibuprofen dilution of 1.25mg/mL produced clear, colourless solutions with no microscopic particles when mixed with all PN/glucose/lipid formulations tested. Ibuprofen was chemically stable with all PN and SMOF lipid admixture, for a period of 4 hours. The zeta potential and particle diameter were within acceptable limits. Ibuprofen lysine was stable over 24 hours in Luer-lok polypropylene syringes. Ibuprofen 1.25mg/mL is physically and chemically compatible with 10% glucose, starter PN, standard preterm and low carbohydrate PN, and SMOF lipid admixture plus vitamins for a period of four hours, which is the maximum time they could be in an admixture during a continuous infusion. [ABSTRACT FROM AUTHOR]

A first of its kind, simple, rapid, and sensitive liquid chromatography mass spectrometry (LC-MS/MS) method was developed and validated for quantification of perindopril and perindoprilat in both human plasma and breast milk. The analytes and internal standards (phenazone and acetyl salicylic acid) were extracted from biological matrices by protein precipitation. A Phenomenex® C-18 column was used to provide an appropriate chromatographic separation of the analytes, followed by detection with tandem mass spectrometry. Gradient chromatographic and mass spectrometric detection conditions with mobile phases (A: 5% methanol + 0.1% formic acid in water v/ v, and B: 95% methanol + 0.1% formic acid in water v/ v) were developed to achieve a LOQ of 0.5 ng/mL in both human plasma and milk. The method was suitable of evaluating clinical samples. The mass transition was followed as m/z 369.10/172.00 for perindopril, m/z 339.00/168.10 for perindoprilat, m/z 188.90/55.95 for phenazone, and m/z 179.04/137.02 for acetyl salicylic acid. The developed method was optimized and validated with a linear range of 0.1-200 ng/mL ( r = better than 0.99 for both perindopril and perindoprilat). The precision and accuracy values were within 15% CV. The overall recovery of the analytes was 80-110%. The method has good specificity and repeatability. Stability studies were conducted in both human plasma and bovine milk for up to 3 months, at the storage conditions of 25, 4, and −80 °C. [ABSTRACT FROM AUTHOR]

Insoluble, nanostructured delta inulin particles enhance the immunogenicity of co-administered protein antigens and consequently are used as a vaccine adjuvant (Advax™). To better understand their immunomodulatory properties, the in vitro hydrolysis and in vivo distribution of delta inulin particles were investigated. Delta inulin particle hydrolysis under bio-relevant acidic conditions resulted in no observable change to the bulk morphology using SEM, and HPLC results showed that only 6.1% of the inulin was hydrolysed over 21 days. However, 65% of the terminal glucose groups were released, showing that acid hydrolysis relatively rapidly releases surface bound chemistries. This was used to explain in vivo biodistribution results in which delta inulin particles surface-labelled with fluorescein-5-thiosemicabizide were administered to mice using intramuscular (I.M.) or subcutaneous (S.C.) routes. Comparison analysis of the fluorescence of soluble inulin in the supernatants of homogenised tissues maintained at room temperature or heated to 100 °C to solubilise particulate inulin was used to distinguish between fluorescent probe on soluble inulin and probe bound to inulin within particles. Following both I.M. and S.C. injection delta inulin exhibited a depot behaviour with local injection site residence for several weeks. Over this time, as injection site inulin reduced, there was measurable transport of intact delta inulin particles by macrophages to secondary lymphoid organs and the liver. Ultimately, the injected delta inulin became solubilised resulting in its detection in the plasma and in the urine. Thus injected delta inulin particles are initially taken up by macrophages at the site of injection, trafficked to secondary lymphoid tissue and the liver, and hydrolysed resulting in their becoming soluble and diffusing into the blood stream, from whence they are glomerularly filtered and excreted into the urine. These results provide important insights into the biodistribution of I.M. or S.C. injected delta inulin particles when used as vaccine adjuvants and their method of excretion. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop an in vitro release model for intramammary drug delivery system (IMDS) evaluation. This study was the first to establish an in vitro–in vivo correlation with investigation of an IMDS containing lasalocid. Three different methods including the standard United States Pharmacopeia dissolution method with apparatus 2, a modified United States Pharmacopeia method using a dialysis bag, or a specifically designed enhancer cell system, were assessed for the release study. Full cream milk and water were selected as the release media. In vivo evaluation was carried out by administering lasalocid IMDS into the udder of lactating Holstein dairy cows. Milk samples were collected and analyzed at selected time points after treatment. Dissolution data were fitted to various kinetic models. The results indicated that the release rate of lasalocid from IMDS was controlled by factors other than diffusion, which could include the sedimentation of lasalocid to the interface and the wetting of lasalocid particles by water at the interface of oil in the formulation and release media. The results obtained in vivo and in vitro were consistent. The in vitro assessment supports formulation design for early stage development and potentially for in vivo performance analysis. [ABSTRACT FROM AUTHOR]

We present a theoretical investigation of high-order harmonics and isolated short attosecond pulse generation by a spatially inhomogeneous combined field. The calculation results show that this spatiotemporally synthesized field can not only extend the spectral cutoff but also realize the quantum path control, whereupon an ultrawide supercontinuum with a smooth and regular structure is generated. By filtering a wide range of continuous harmonics around the cutoff region, an isolated 17.6 as pulse with a bandwidth of 279 eV is directly obtained without any phase compensation. Moreover, we also investigate the influence of the CEP, time delay, spatial nonhomogeneity, and laser intensity on the harmonic spectrum. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel RID-HPLC method development for NAR quantification without derivatization. • Forced degradation was performed to detect degradation peaks and stability of NAR. • The developed method was validated as per FDA guidelines and applied to feed premix. • Greenness profile of the developed method was evaluated using GAPI and AGREE tools. Narasin (NAR) is a commonly used ionophoric antibiotic used in the poultry industry, cattle and pig production both for treating coccidiosis and increasing feed conversion efficiency. To ensure safe administration of NAR into the feed is important to avoid toxicity to farm animals caused by incorporation of large doses or non-homogenous mixing, which requires a simple and sensitive chromatographic method to quantify NAR. However, NAR detection by HPLC is challenging as it lacks a chromophore making it less susceptible to UV and fluorescence detection, and the published analytical methods suffer from disadvantages such as the need for complex derivatization or the use of high volumes of hazardous organic solvents. Herein, a novel, simple, rapid, and cost-effective HPLC method is reported to quantify NAR and a study of forced degradation under acidic, basic, temperature, and oxidative conditions are proposed. The separation was performed using a Phenomenex C18 analytical column (4.6 × 150 mm, 5 μm) and the mobile phase composed of 920 mL methanol, 80 mL water and 10 mL glacial acetic acid. A flow rate of 1 mL/min, and sample injection volume of 50 μL was used to detect NAR using the refractive index detector. The HPLC method was validated according to FDA guidelines and was found to be accurate, precise, sensitive and robust. It was shown to be linear at ranges of 200 to 900 µg/mL with a limit of detection (LOD) and limit of quantitation (LOQ) of 7.1 µg/mL and 21.5 µg/mL respectively. The method was successfully used to quantify the drug in its commercial formulation and a forced degradation study was performed under acidic, basic, temperature, and oxidative conditions. The greenness profile of the method was also investigated and compared to reported methods using the green analytical procedure Index (GAPI), and Analytical GREEnness Metric Approach and Software (AGREE) tools. The results indicated the greenness of the developed method. [ABSTRACT FROM AUTHOR]

[Display omitted] Adjuvant chemotherapy is highly recommended for liver cancer to enhance survival rates due to its tendency to recur frequently. Localized drug-eluting implants have gained traction as an alternative to overcome the limitations of systemic chemotherapy. This work describes the development of biodegradable 3D printed (3DP) bilayer films loaded with 5-fluorouracil (5FU) and cisplatin (Cis) with different infill percentages where the 5FU layers were 40%, 30%, and 30% and Cis layers were 10%, 15%, and 10% for films A, B, and C, respectively. The relevant characterization tests were performed, and the drug content of films was 0.68, 0.50, and 0.50 mg of 5FU and 0.39, 0.80, and 0.34 mg of Cis for films A, B, and C, respectively. Cis release was affected by the alterations to the film design, where films A, B, and C showed complete release at 12, 14, and 23 days, respectively. However, 5FU was released over 24 h for all films. The films were stable for up to two weeks after storage at 25 °C/65% relative humidity and four weeks at 4 °C where drug content, tensile strength, FTIR, and thermal analysis results demonstrated negligible alterations. The cytotoxicity of the films was assessed by MTS assays using HepG2 cell lines demonstrating up to 81% reduction in cell viability compared to blank films. Moreover, apoptosis was confirmed by Western Blots and the determination of mitochondrial cell potential, highlighting the potential of these films as a promising approach in adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Abstract: We report on a porous silica–lipid hybrid microcapsule (SLH) oral delivery system for indomethacin fabricated from Pickering emulsion templates, where the drug forms an electrostatic complex with cationic lipid present in the oil phase. Dry SLH microcapsules prepared either by spray drying (∼1–5µm) or phase coacervation (20–50µm) exhibit a specific internal porous matrix structure with pore diameters in the range of 20 to 100nm. Dissolution studies under sink conditions and in the presence of electrolytes revealed a decreased extent of dissolution; this confirms the lipophilic nature the drug–lipid complex and its location in the oil phase. Orally dosed in - vivo studies in rats showed complete drug absorption and statistically higher fasted state bioavailability (F) (p <0.05) in comparison to aqueous suspensions and o/w submicron emulsions of indomethacin. It is postulated that the SLH microcapsules improve oral absorption via complete solubilisation of drug–lipid electrostatic complexes during enzymatic lipolysis in the GI track. [Copyright &y& Elsevier]

[Display omitted] • Novel green chromatographic method for the simultaneous determination of 5-fluorouracil and cisplatin. • Evaluation of the greenness profile using NEMI, GAPI, Eco-scale and AGREE tools. • Application of a newly developed HPLC method to evaluate the drug release of co-loaded 5-fluorouracil and cisplatin films. The combination of 5-fluorouracil (5-FU) and cisplatin (Cis) has been used for the treatment of many cancers. The combination demonstrates synergy and improved clinical outcomes encouraging developing a formulation with both drugs. An analytical procedure is essential for formulation studies; however, no method has been reported for the concurrent determination and quantification of both 5-FU and Cis to date. A novel, simple, accurate, and precise HPLC method was developed using a C 18 column (250 mm × 4.6 mm, 5 µm) and mobile phase composed of 0.5 mM sodium dodecyl sulfate: methanol (98:2, v/v), adjusted to pH 2.5 with phosphoric acid. A flow rate of 0.5 mL/min was applied and a photodiode array was utilized for detection and the retention times were 9.89 min (265 nm) for 5-FU and 5.36 min (210 nm) for Cis. Validation procedures were performed, and the method was found to be linear at ranges of 0.9–60.0 µg/mL for 5-FU and 6.0–60.0 µg/mL for Cis. The limits of detection (LOD) and quantitation (LOQ) were 0.10 and 0.25 µg/mL for 5-FU and 2.00 and 4.00 µg/mL for Cis, respectively. Other parameters such as precision, selectivity, robustness, and stability results were within acceptable limits. The method was applied to a model co-eluting film and its release profile was studied. Additionally, the method's greenness was evaluated by four assessment tools namely the national environmental method index (NEMI), analytical eco scale assessment (ESA), green analytical procedure index (GAPI), and Analytical GREEnness Metric Approach and Software (AGREE). The results demonstrated compliance with green analytical chemistry (GAC) practices. This research acts as a step towards further investigation of drug stability under different stress conditions and quantification of the intact drugs in presence of their degradation products. [ABSTRACT FROM AUTHOR]

An innovative single NIR light-triggered PTT and PDT nanoplatform from the conventional phototherapeutic agents of Ce6 and CuS NPs was achieved via a core–shell structure strategy. [Display omitted] Theranostic nanoplatforms integrating simultaneously photodynamic therapy (PDT) and photothermal therapy (PTT) exhibit intrinsic advantages in tumor therapy due to distinct mechanisms of action. However, it is challenging to achieve PDT and PTT under single near-infrared (NIR) laser irradiation with a nanoplatform utilizing conventional organic photodynamic agent and inorganic photothermal agent owing to the difference in inherent excitation wavelengths. Particularly, the single NIR light (660 nm)-triggered PTT and PDT nanoplatform, constructed from chlorin e6 (Ce6) and copper sulfide (CuS) nanoparticles (NPs), has never been reported. Herein, we, for the first time, designed and established a dual-modal phototherapeutic nanoplatform that achieved both PTT and PDT under single NIR laser (660 nm) irradiation for Ce6 and CuS NPs with the strategy of core–shell structured CuS@Carbon integrated with Ce6. Introducing of carbon shell not only endows small CuS NPs with excellent tumor accumulation, but also significantly strengthens the photothermal performance of CuS NPs, realizing efficient photothermal performance under 660 nm laser irradiation. Moreover, Ce6 in carbon shell endowed the nanoplatform with photodynamic effect under 660 nm laser irradiation. The as-prepared Ce6/CuS@Carbon nanoplatform thus achieved dual-modal phototherapy under single NIR laser irradiation, significantly inhibiting tumor growth with minimal adverse effects and superior biosafety. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is one of the leading causes of death from cancer in women; second only to lung cancer. Tamoxifen (TAM) is a hydrophobic anticancer agent and a selective estrogen modulator (SERM), approved by the FDA for hormone therapy of BC. Despite having striking efficacy in BC therapy, concerns regarding the dose-dependent carcinogenicity of TAM still persist, restricting its therapeutic applications. Nanotechnology has emerged as one of the most important strategies to solve the issue of TAM toxicity, owing to the ability of nano-enabled-formulations to deliver smaller concentrations of TAM to cancer cells, over a longer period of time. Various TAM-containing-nanosystems have been successfully fabricated to selectively deliver TAM to specific molecular targets found on tumour membranes, reducing unwanted toxic effects. This review begins with an outline of breast cancer, the current treatment options and a history of how TAM has been used as a combatant of BC. A detailed discussion of various nanoformulation strategies used to deliver lower doses of TAM selectively to breast tumours will then follow. Finally, a commentary on future perspectives of TAM being employed as a targeting vector, to guide the delivery of other therapeutic and diagnostic agents selectively to breast tumours will be presented. [ABSTRACT FROM AUTHOR]

Stents are currently the primary choice for the treatment of both vascular and non-vascular occlusions and/or stenosis. Despite the proven history of clinical safety and efficacy, the benefit of traditional vascular or non-vascular stenting is often limited by in-stent restenosis, resulting in failure of existing stent or reintervention by use of another stent. Coronary drug-eluting stents (DESs) significantly reduce restenosis of vascular stents and have revolutionised the percutaneous coronary intervention (PCI) treatment in coronary stenting patients. Following the similar concept of coronary DESs, non-vascular DESs are being investigated to reduce non-vascular restenosis caused by tumour growth, enhance stenting functions, and increase their effectiveness in the treatment of obstructive gastrointestinal (GI) cancers. This article summarises and updates the outcomes of preclinical and clinical studies on non-vascular DESs for localised management of malignant GI obstructions with emphasis on fabrication techniques and regulatory requirements relevant to development and marketing approval. Unlabelled Image [ABSTRACT FROM AUTHOR]

Abstract Faulty bony repair causes dysrepair of injured growth plate cartilage and bone growth defects in children; however, the underlying mechanisms are unclear. Recently, we observed the prominent induction of neurotrophin‑3 (NT-3) and its important roles as an osteogenic and angiogenic factor promoting the bony repair. The current study investigated its roles in regulating injury site remodelling. In a rat tibial growth plate drill-hole injury repair model, NT-3 was expressed prominently in osteoblasts at the injury site. Recombinant NT-3 (rhNT-3) systemic treatment enhanced, but NT-3 immunoneutralization attenuated, expression of cartilage-removal proteases (MMP-9 and MMP-13), presence of bone-resorbing osteoclasts and expression of osteoclast protease cathepsin K, and remodelling at the injury site. NT-3 was also highly induced in cultured mineralizing rat bone marrow stromal cells, and the conditioned medium augmented osteoclast formation and resorptive activity, an ability that was blocked by presence of anti-NT-3 antibody. Moreover, NT-3 and receptor TrkC were induced during osteoclastogenesis, and rhNT-3 treatment activated TrkC downstream kinase Erk1/2 in differentiating osteoclasts although rhNT-3 alone did not affect activation of osteoclastogenic transcription factors NF-κB or NFAT in RAW 264.7 osteoclast precursor cells. Furthermore, rhNT-3 treatment increased, but NT-3 neutralization reduced, expression of osteoclastogenic cytokines (RANKL, TNF-α, and IL-1) in mineralizing osteoblasts and in growth plate injury site, and rhNT-3 augmented the induction of these cytokines caused by RANKL treatment in RAW 264.7 cells. Thus, injury site osteoblast-derived NT-3 is important in promoting growth plate injury site remodelling, as it induces cartilage proteases for cartilage removal and augments osteoclastogenesis and resorption both directly (involving activing Erk1/2 and substantiating RANKL-induced increased expression of osteoclastogenic signals in differentiating osteoclasts) and indirectly (inducing osteoclastogenic signals in osteoblasts). Graphical abstract Unlabelled Image Highlights • Injury site osteoblast-derived NT-3 has both direct and indirect roles in promoting growth plate injury site remodeling. • NT-3 enhances expression of MMP-9 and MMP-13 and osteoclast recruitment and function at the growth plate injury site. • NT-3 was induced in mineralizing BMSCs, and the conditioned medium augmented osteoclastogenesis and resorptive activity. • NT-3 can induce osteoclastogenic cytokines and RANKL in osteoblasts. • NT-3 and TrkC were induced, and rhNT-3 treatment activated TrkC downstream kinase Erk1/2 in differentiating osteoclasts. [ABSTRACT FROM AUTHOR]

Background Topical antimicrobial preparations are of utmost importance in treating suspected and confirmed meticillin-resistant Staphylococcus pseudintermedius ( MRSP) infections due to the increasing incidence of widespread resistance to systemic antimicrobials. Lasalocid is active against MRSP in vitro and this may become an important topical antimicrobial for the treatment of canine pyoderma. Hypothesis/Objectives To determine effects of various formulation types on penetration and retention of lasalocid applied to canine skin in vitro. Animals Normal canine skin was collected from the thorax of five dogs that had been euthanized on the basis of health and/or intractable behavioural issues. Methods Solution, lotion and ointment containing 2% lasalocid were applied to ex vivo canine skin. Transdermal penetration was assessed for a 24 h period and retention of lasalocid was assessed at the conclusion of the study. Results The solution had significantly higher skin retention of lasalocid and proportion of applied dose retained in skin than lotion and ointment (Tukey-Kramer Honest Significant Difference test, P < 0.01). Lasalocid could not be detected in the receptor fluid of any Franz cell at any time point. Conclusions and clinical importance Lasalocid was not identified in the receptor fluid of any sample, indicating that systemic absorption of the active ingredient in vivo is unlikely. Lasalocid may be useful in the treatment of MRSP infections if in vivo studies support safety and efficacy. [ABSTRACT FROM AUTHOR]

Flightless I (Flii) is an actin remodeling protein important for cytoskeletal regulation and cellular processes including migration, proliferation, and adhesion. Previous studies have clearly identified Flii as a novel therapeutical target for improved wound repair and have demonstrated Flii regulation using Flii neutralizing antibodies (FnAb) in different models of wound healing in vivo . Here we describe the development of an optimized topical delivery system that can neutralize Flii activity in the epidermis. Topical delivery of FnAb is an attractive approach as it provides a convenient application, sustained release, localized effect, and reduced dosage. Three successful formulations were developed, and their physical and chemical stability examined. The in vitro release revealed prolonged and sustained release of FnAb in all the tested formulations. Additionally, penetration studies using intact porcine skin showed that FnAb penetrated the epidermis and upper papillary dermis. The penetrated FnAb significantly reduced Flii expression compared to dosed matched IgG controls. This study has successfully developed a topical delivery system for FnAb that could serve as a potential platform for future localized wound treatments. [ABSTRACT FROM AUTHOR]

Targeting drug carrier systems based on graphene oxide (GO) are of great interest, since it can selectively deliver anticancer drugs to tumor cells, and enhance therapeutic activities with minimized side effects. However, direct grafting target molecules on GO usually results in aggregation of physiological fluid, limiting its biomedical applications. Here, we propose a new strategy to construct targeting GO drug carrier using folic acid grafted bovine serum albumin (FA-BSA) as both the stabilizer and targeting agent. FA-BSA decorated graphene oxide-based nanocomposite (FA-BSA/GO) was fabricated by the physical adsorption of FA-BSA on GO, which was developed as a targeting drug delivery carrier. FA-BSA/GO as the drug carrier was associated with anticancer drug doxorubicin (DOX) through π-π and hydrogen-bond interactions, resulting in high drug loading (up to 437.43 μg DOX/mg FA-BSA/GO). FA-BSA/GO/DOX systems demonstrated pH responsive and sustained drug release. The hemolysis ratio of FA-BSA/GO was less than 5%, demonstrating its safety as drug carrier for intravenous injection. Moreover, in vitro cell cytotoxicity and cellular uptake analysis suggested that the constructed FA-BSA/GO/DOX nanohybrids could significantly enhance the anticancer activity. The present work has confirmed the potential for fabrication of highly stable and dispersible GO-based targeting delivery systems for efficient cancer therapy. [ABSTRACT FROM AUTHOR]

[Display omitted] • pH is vital for the normal functioning of the body. • Drug targeting has been widely used to increase efficacy and reduce adverse effects. • pH variation in different tissues and change in pH in some diseased tissues has been used as an opportunity to deliver drugs. • pH-responsive drug delivery is an attractive platform for targeted drug delivery. Physiologic pH is vital for the normal functioning of tissues and varies in different parts of the body. The varying pH of the body has been exploited to design pH-sensitive smart oral, transdermal and vaginal drug delivery systems (DDS). The DDS demonstrated promising results in hard-to-treat diseases such as cancer and Helicobacter pylori infection. In some cases, a change in pH of tissues or body fluids has also been employed as a useful diagnostic biomarker. This paper aims to comprehensively review the development and applications of pH-sensitive DDS as well as recent advances in the field. [ABSTRACT FROM AUTHOR]

Drug combinations are widely employed in chemotherapy for colorectal cancer treatment. However, traditional cocktail combination in clinic causes the uncertainty of the treatment, owing to varying pharmacokinetics of different drugs. The aim of this study was to design co-loaded liposomes to achieve the synchronised delivery and release. Oxaliplatin and irinotecan hydrochloride, as one of recommended combination schemes for the treatment of colorectal cancer in clinic, were co-loaded into the liposomes. The particle sizes of the liposomes were < 200 nm with uniform size distribution. In vitro release study showed that both drugs could be synchronously released from the liposomes, which means the optimized synergistic ratio of two drugs could be achieved. In vitro cellular uptake revealed that co-loaded liposomes could efficiently deliver different drugs into the same cells, indicating their potential as carriers for enhancing the cancer therapy. CLSM images of cryo-sections for in vivo co-delivery study also revealed that co-loaded liposomes had superior ability to co-deliver both the cargoes into the same tumor cells. Besides, in vivo NIRF imaging indicated that the liposomes could increase the drug accumulation in tumor compared with free drug. In vitro cytotoxicity evaluation demonstrated that co-loaded liposomes exhibited higher cytotoxicity than the mixture of single loaded liposomes in both CT-26 and HCT-116 cells. Furthermore, co-loaded liposomes also presented superior anti-tumor activity in CT-26 bearing BALB/c mice. In vivo safety assessment demonstrated that liposomes had lower toxicities than their solution formulations. These results indicated that oxaliplatin and irinotecan hydrochloride co-loaded liposomes would be an efficient formulation for improving colorectal cancer therapy with potential clinical applications. [ABSTRACT FROM AUTHOR]

In this paper, we successfully synthesized folate-modified pH-sensitive copolymer methoxy-poly(ethylene glycol) 2K -poly(ε-caprolactone) 4K -poly(glutamic acid) 1K (mPEG 2K -PCL 4K -PGA 1K -FA), which could form the polymeric assembly in an aqueous solution, for co-delivering hydrophilic drugs doxorubicin hydrochloride (DOX) and verapamil hydrochloride (VER) (FA-poly(DOX+VER)). Since VER was an effective P-glycoprotein inhibitor, the combination of DOX and VER could reverse the multidrug resistance efficiently and enhance the therapeutic effect. Therefore, the inhibition ratios of MCF-7/ADR resistant cancer cell treated by FA-poly (DOX+VER) were almost more than 30% higher than those of FA-polyDOX after 48 h and 72 h. Furthermore, the conjugation of FA could lead the co-delivery systems actively targeting into the FA receptor over-expressing cancer cells in addition to the passive accumulation of the assembly in tumor tissues. Importantly, the prepared mPEG 2K -PCL 4K -PGA 1K -FA assembly showed high pH-sensitive property, which made the drugs mostly released in tumor tissue (acid environment) than in physiological environment (neutral environment). In summary, the as-prepared co-delivery system FA-poly(DOX+VER) demonstrated a high efficiency in reversing the multidrug resistance and targeting FA receptor to improve the anticancer effect of DOX in MCF-7/ADR resistant cells. [ABSTRACT FROM AUTHOR]

The swine industry has evolved significantly in the recent decades, but this has come at considerable expense to piglet survival. Breeding sows for greater prolificacy has been accompanied by a greater proportion of piglets being born underweight, of lower vigor, and higher susceptibility to early mortality. Inducing sows to farrow during working hours has the potential to increase piglet survivability, but non-therapeutic injectable products are often discouraged on farms. We aimed to design and develop a novel vaginal drug delivery system (NVDDS) that could reliably trigger luteolysis and induce parturition. To achieve this, two vaginal tablets containing the luteolytic agent cloprostenol were formulated to be inserted together: one would release constituents immediately on insertion (immediate release; IR) and the other would release cloprostenol in a controlled manner (controlled release; CR). The two formulations (IR and CR) were evaluated for drug release, swelling and bio-adhesion in conditions simulating the sow vaginal environment. The IR tablet released the drug completely for 5 min whereas the CR tablet took 5 h to release 50% of the drug. Furthermore, the release kinetics were evaluated by fitting the dissolution profiles into different mathematical models. Both IR and CR tablets were best fitted by the Makoid–Banakar model which assumes release by summation of different mechanisms. The performance of the optimized formulations was studied in vivo with 161 Large White x Landrace sows of varying parity (0–5). The sows were assigned to five groups. Group 1 (SI) received a single vulval injection of cloprostenol at 0700 h (n = 32), group 2 (SDI) received the same dose split in two parts, at 0700h and 1300h (n = 33). Group 3 (IRT) animals were administered an IR tablet at 0700h (n = 32), while group 4 (IRCRT) received both IR and CR tablets at 0700 h (n = 33). Group 5 was untreated and served as a control (n = 32). The interval to farrowing was longer (p < 0.001) for controls than for treated sows, but there were no differences among cloprostenol treatments for timing of farrowing. The finding confirms the efficacy of the NVDDS for induction of farrowing in sows. [ABSTRACT FROM AUTHOR]

[Display omitted] • Drug-in-adhesive patches containing 5-fluorouracil for the treatment of skin cancer. • Pressure-sensitive adhesives using Eudragit® E and plasticizers for topical application. • Solubility parameters and thermal analysis for polymer-plasticizer miscibility evaluation. Topical patches containing 5-fluorouracil (5-FU) are a feasible alternative to overcome the shortcomings of commercial cream for the treatment of non-melanoma skin cancer (NMSC). Plasticizers are a critical component of drug-in-adhesive (DIA) patches as they can significantly affect the mechanical, adhesive and drug release characteristics of the patches. Eudragit® E (EuE) is a methacrylate-based cationic copolymer capable of producing flexible and adhesive films for topical application. In this study, the effect of plasticizers on the mechanical, adhesive and 5-FU release characteristics of EuE-based patches was comprehensively evaluated. While the elongation at break (%) and adhesion of the films were significantly increased with increasing triacetin, dibutyl sebacate (DBS) and triethyl citrate (TEC) concentrations, the tensile strength showed an inverse relationship. EuE plasticized with 40% triacetin, 30% DBS or 40% w/w TEC produced elastic and adhesive films most suitable for topical application. In vitro release studies of the 5-FU-loaded patches demonstrated an initial burst release pattern during the first 10 min followed by a slow release over 120 min. In summary, this study provides important information on effect of plasticizers for preparation of EuE-based patches with desired mechanical, adhesive and release characteristics of 5-FU towards their potential application in the treatment of NMSC. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) printing is among the rapidly evolving technologies with applications in many sectors. The pharmaceutical industry is no exception, and the approval of the first 3D-printed tablet (Spiratam®) marked a revolution in the field. Several studies reported the fabrication of different dosage forms using a range of 3D printing techniques. Thermosensitive drugs compose a considerable segment of available medications in the market requiring strict temperature control during processing to ensure their efficacy and safety. Heating involved in some of the 3D printing technologies raises concerns regarding the feasibility of the techniques for printing thermolabile drugs. Studies reported that semi-solid extrusion (SSE) is the commonly used printing technique to fabricate thermosensitive drugs. Digital light processing (DLP), binder jetting (BJ), and stereolithography (SLA) can also be used for the fabrication of thermosensitive drugs as they do not involve heating elements. Nonetheless, degradation of some drugs by light source used in the techniques was reported. Interestingly, fused deposition modelling (FDM) coupled with filling techniques offered protection against thermal degradation. Concepts such as selection of low melting point polymers, adjustment of printing parameters, and coupling of more than one printing technique were exploited in printing thermosensitive drugs. This systematic review presents challenges, 3DP procedures, and future directions of 3D printing of thermo-sensitive formulations. [ABSTRACT FROM AUTHOR]

Inulin's unique and flexible structure, stabilization/protective effects, and organ targeting ability make it an excellent drug delivery carrier compared to other biodegradable polysaccharides. The three hydroxyl groups attached to each fructose unit serve as an anchor for chemical modification. This, in turn, helps in increasing bioavailability, improving cellular uptake, and achieving targeted, sustained, and controlled release of drugs and biomolecules. This review focuses on the various types of inulin drug delivery systems such as hydrogel, conjugates, nanoparticles, microparticles, micelles, liposomes, complexes, prodrugs, and solid dispersion. The preparation and applications of the different inulin drug delivery systems are further discussed. This work highlights the fact that modification of inulin allows the use of this polymer as multifunctional scaffolds for different drug delivery systems. [ABSTRACT FROM AUTHOR]

As a variety of novel technologies, 3D printing has been considerably applied in the field of health care, including cancer treatment. With its fast prototyping nature, 3D printing could transform basic oncology discoveries to clinical use quickly, speed up and even revolutionise the whole drug discovery and development process. This literature review provides insight into the up-to-date applications of 3D printing on cancer research and treatment, from fundamental research and drug discovery to drug development and clinical applications. These include 3D printing of anticancer pharmaceutics, 3D-bioprinted cancer cell models and customised nonbiological medical devices. Finally, the challenges of 3D printing for cancer applications are elaborated, and the future of 3D-printed medical applications is envisioned. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To compare pharmacokinetics of intravenous breviscapine liposomes in Beagle dogs, rabbits and rats. Methods: Six Beagle dogs, 6 rabbits and 12 rats were intravenously administrated with breviscapine liposomes and commercial injection (breviscapine solution) by the crossover design (two periods), respectively. Plasma concentration of scutellarin, the main active component in breviscapine, at different time intervals was determined by reverse phase-HPLC. The pharmacokinetic parameters including area under the curve (AUC), clearance (CL(s)) and volume of distribution (V (c)) were calculated. Results: The plasma concentration–time profiles were fitted to a two-compartment model. Breviscapine liposomes exhibited significant difference from injection in CL(s) and AUC, examined by a one-way analysis of variance (ANOVA). With regard to both breviscapine liposomes and commercial injection (free breviscapine), the logarithm values of AUC, CL(s) and V (c) were all related to the logarithm of the body weight by the allometric equation: Y = a × W b . Conclusion: The allometric equation might be applied to extroplate dosage for human from animal data and also for dosage adjustment of breviscapine liposomes in order to achieve same AUC as commercial injection. Compared with the breviscapine solution, breviscapine liposomes delivered more scutellarin into the plasma. [Copyright &y& Elsevier]

For several decades, self-expanding metal stents (SEMSs) have shown significant clinical success in the palliation of obstructive metastatic oesophageal cancer. However, these conventional oesophageal stents can suffer from stent blockage caused by malignant tumour cell growth. To overcome this challenge, there is growing interest in drug-releasing stents that, in addition to palliation, provide a sustained and localized release of anticancer drugs to minimise tumour growth. Therefore, in this study we prepared and evaluated an oesophageal stent-based drug delivery platform to provide the sustained release of docetaxel (DTX) for the treatment of oesophageal cancer-related obstructions. The DTX-loaded oesophageal stents were fabricated via dip-coating of bare nitinol stents with DTX-polyurethane (PU) solutions to provide PU coated stents with DTX loadings of 1.92 and 2.79% w/w. Mechanical testing of the DTX-PU coated stents revealed that an increase in the drug loading resulted in a reduction in the ultimate tensile strength, toughness and Young's modulus. In vitro release studies showed a sustained release of DTX, with ~80–90% released over a period of 33 days. While the DTX-loaded stents exhibited good stability to gamma radiation sterilisation, UV sterilisation or accelerated storage at elevated temperatures (40 °C) resulted in significant DTX degradation. Cell proliferation, apoptosis and Western blotting assays revealed that the DTX released from the stents had comparable anticancer activity to pure DTX against oesophageal cancer cells (KYSE-30). This research demonstrates that the dip-coating technique can be considered as a promising approach for the fabrication of drug-eluting stents (DESs) for oesophageal cancer treatment. [ABSTRACT FROM AUTHOR]

Self-expanding metal stents (SEMSs) are currently the gold standard for the localised management of malignant gastrointestinal (GI) stenosis and/or obstructions. Despite encouraging clinical success, in-stent restenosis caused by tumour growth is a significant challenge. Incorporating chemotherapeutic drugs into GI stents is an emerging strategy to provide localised and sustained release of drugs to intestinal malignant tissues to prevent tumour growth. Therefore, the aim of this work was to develop and evaluate a local GI stent-based delivery system that provides a controlled release of 5-fluorouracil (5FU) over a course of several weeks to months, for the treatment of colorectal cancer and cancer-related stenosis/obstructions. The 5FU-loaded GI stents were fabricated via sequential dip-coating of commercial GI stents with a drug-loaded polyurethane (PU) basecoat and a drug-free poly(ethylene-co-vinyl acetate) (PEVA) topcoat. For comparison, two types of commercial stents were investigated, including bare and silicone (Si) membrane-covered stents. The physicochemical properties of the 5FU-loaded stents were evaluated using photoacoustic Fourier-transform infrared (PA-FTIR) spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and thermal analysis. In vitro release studies in biological medium revealed that the 5FU-loaded stents provided a sustained release of drug over the period studied (18 d), and cell viability, cell cycle distribution and apoptosis assays showed that the released 5FU had comparable anticancer activity against human colon cancer cells (HCT-116) to pure 5FU. This study demonstrates that dip-coating is a facile and reliable approach for fabricating drug-eluting stents (DESs) that are promising candidates for the treatment of GI obstructions and/or restenosis. [ABSTRACT FROM AUTHOR]

Conventional chemotherapies used for breast cancer (BC) treatment are non-selective, attacking both healthy and cancerous cells. Therefore, new technologies that enhance drug efficacy and ameliorate the off-target toxic effects exhibited by currently used anticancer drugs are urgently needed. Here we report the design and synthesis of novel mesoporous silica nanoparticles (MSNs) equipped with the hormonal drug tamoxifen (TAM) to facilitate guidance towards estrogen receptors (ERs) which are upregulated in breast tumours. TAM is linked to the MSNs using a poly-ʟ-histidine (PLH) polymer as a pH-sensitive gatekeeper, to ensure efficient delivery of encapsulated materials within the pores. XRD, HR-TEM, DLS, SEM, FT-IR and BET techniques were used to confirm the successful fabrication of MSNs. The MSNs have a high surface area (>1000 m2/g); and a mean particle size of 150 nm, which is an appropriate size to allow the penetration of premature blood vessels surrounding breast tumours. Successful surface functionalization was supported by FT-IR, XPS and TGA techniques, with a grafting ratio of approximately 29%. The outcomes of this preliminary work could be used as practical building blocks towards future formulations. [ABSTRACT FROM AUTHOR]

Despite the promising properties of tea tree oil (TTO) as potential therapeutics for several superficial skin conditions, certain limitations such as physical instability and skin irritation have restricted its widespread use. This study focuses on developing a rationally designed lipid-based nanoformulation (TTO-LNF) in accordance with the US Food and Drug Administration standard using a well-recognized quality-by-design (QbD) approach. Using a mixture experimental design, TTO-LNF has been optimized with 5% TTO, 10% surfactant, 5% co-surfactant, and 80% water, which showed a 14.4 ± 4.4 nm droplet size and 0.03 ± 0.01 polydispersity index (PDI). To ease the topical administration, the TTO-LNF gel formulation was further developed using xanthan gum to achieve the desired viscosity and form a gel. The in vitro antibacterial tests of TTO-LNF showed promising inhibitory effects toward both Gram-negative and Gram-positive bacteria. In fact, a complete growth inhibition of S. epidermidis was observed when exposed to TTO-LNF and TTO-LNF gel for 24 h, showing better activity than antibiotic kanamycin (25 µg/mL). Additionally, the in vitro release study showed a sustained release profile with a 50% release in 24 h, which could be beneficial to reduce the toxicity and thereby improve the therapeutic efficacy for long-acting applications. Furthermore, the formulations were remarkably stable at 40 °C/75% Relative humidity (RH) for at least 4 weeks. Therefore, this study presents a promising strategy to develop a biocompatible and stable formulation that can be used for the topical treatment of skin infections. [ABSTRACT FROM AUTHOR]

This paper reports the oxidation of inulin using varying ratios of sodium periodate and the characterization of the inulin polyaldehyde. The physicochemical properties of the inulin polyaldehyde (oxidized inulin) were characterized using different techniques including 1D NMR spectroscopy, 13C Nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), differential scanning calorimetric (DSC), ultraviolet-visible spectroscopy (UV), and scanning electron microscopy (SEM). The aldehyde peak was not very visible in the FTIR, because the aldehyde functional group exists in a masked form (hemiacetal). The thermal stability of the oxidized inulin decreased with the increasing oxidation degree. The smooth spherical shape of raw inulin was destructed due to the oxidation, as confirmed by the SEM result. The 1HNMR results show some new peaks from 4.8 to 5.0 as well as around 5.63 ppm. However, no aldehyde peak was found around 9.7 ppm. This can be attributed to the hemiacetal. The reaction of oxidized inulin with tert-butyl carbazate produced a carbazone conjugate. There was clear evidence of decreased peak intensity for the proton belonging to the hemiacetal group. This clearly shows that not all of the hemiacetal group can be reverted by carbazate. In conclusion, this work provides vital information as regards changes in the physicochemical properties of the oxidized inulin, which has direct implications when considering the further utilization of this biomaterial. [ABSTRACT FROM AUTHOR]