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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]

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]

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]

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]

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]

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]

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]

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]

Functionalized nanoparticles have played a major role in the field of targeted therapy, owing to their ability to control the release and for the selective delivery of entrapped materials to tumours. In this work, we described the loading capacity and in vitro release kinetics of mesoporous silica nanoparticles (MSNs), functionalized with Poly-L-Histidine and Tamoxifen. The model drug Doxorubicin (DOX) was successfully encapsulated into MSN-based systems, using the technique of solvent immersion. A post-surface grafting loading method was investigated on functionalized systems, with DOX loading content determined using HPLC. Dialysis bag diffusion was employed to investigate the release kinetics of DOX-loaded-systems at pH 7.4 and 5. The amount of DOX released from native MSNs systems over a 72 h period at pH 5 was approximately 40%; and at pH 7.4 ≈ 30%. A moderate pH dependent release behaviour was observed with both our functionalized systems: DOX@MSN-PLH and DOX@MSN-PLH-TAM; with approximately 5% of DOX released from DOX@MSN-PLH-TAM at pH 7.4 and about 9% released at pH 7.4 over 72 h. The maximal cumulated release of DOX molecules from DOX@MSN-PLH after 72 h was ≈18% at pH 7.4 and ≈23% at pH 5, respectively. The outcome of this work offers a promising contribution towards building future stimuli-responsive nano-drug delivery systems. [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]

Background: Atenolol lactation information is limited, and controversy exists over the safety of its use during breastfeeding. In this study, important parameters including milk-to-plasma ratio, ratio of infant plasma to maternal plasma, infant daily dosage, and relative infant dose were investigated. The findings from this study add information to existing data about atenolol transfer in human milk. This may help guide health professionals in decision making regarding the safety of beta blockers used by mothers during breastfeeding. Research aim: The aims of the study were to quantify concentrations of atenolol in human plasma and milk, to evaluate atenolol pharmacokinetics in lactating women, and to investigate subsequent infant exposure to atenolol via mother’s milk. Methods: In this prospective, longitudinal observational study, participants were lactating mothers (N = 3), 1 to 4 months postpartum, who had been taking atenolol for therapeutic reasons, and one 4-month-old breastfed infant. Eight milk samples were collected over 24 hr at different time points, together with a single blood sample from each lactating mother and the infant, and quantified using a new sensitive liquid chromatography mass spectrometry method developed for this study. Results: Peak milk concentrations of atenolol were observed in the women at 4 hr (Tmax) after oral administration. The dose-normalized maximum concentrations (Cmax) of all patients were similar. The mean milk-to-plasma ratio of the patients who were taking 25 to 100 mg of atenolol was 8.57%. In the mother–infant pair study, the ratio (%) of infant plasma drug concentration to maternal plasma drug concentration observed (18.87%) was similar to the relative infant dose estimated (18.20%). The relative infant dose values (13.96%-18.20%) for all patients were within 10% to 25% of maternal dosage. Conclusion: Atenolol use during breastfeeding should be undertaken with some precaution. If clinically indicated, an alternate beta blocker may be preferred. [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]

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