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Controlled drug release systems are pivotal in optimizing therapeutic outcomes and mitigating side effects in treatment protocols. While traditional delivery vectors such as liposomes, micro/nanoparticles, and microspheres are effective, they often struggle with consistency in drug release rates. This study addresses these issues by integrating stimuli-responsive elements specifically magnetic, thermal, and pH-responsive components into drug delivery systems for precise control. Central to our approach is the use of silk fibroin (SF), chosen for its superior biocompatibility and tunable degradation kinetics. We developed uniform carrier microspheres (CMs) by embedding polydopamine nanoparticles (PDA NPs) into SF microspheres using a custom-designed microfluidic platform. The development process and the application of this platform are detailed, highlighting the precision in control achievable. These CMs showcased enhanced photothermal effects, with the thermal response finely adjustable by altering the PDA NPs concentration, achieving a notable temperature increase of 24.5 ° C at 7.4 wt% concentration. High drug loading capacity (7.5%) and encapsulation efficiency (91.6%) were achieved, along with a pH-responsive release profile under near-infrared irradiation, paving the way for targeted anticancer drug delivery systems using the model drug doxorubicin hydrochloride. These findings underscore the potential of the developed CMs for external topical application, offering promising prospects for targeted cancer therapy utilizing drug-loaded microspheres., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

An electro-chemo-responsive carrier has been engineered for the controlled release of a highly hydrophilic anticancer peptide, CR(NMe)EKA (Cys-Arg- N-methyl-Glu-Lys-Ala). Remotely controlled on demand release of CR(NMe)EKA, loaded in electro-responsive poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles, has been achieved by applying electrical stimuli consisting of constant positive (+0.50 V) or negative voltages (-0.50 V) at pre-defined time intervals. In addition, after loading CR(NMe)EKA/PEDOT nanoparticles into an injectable pH responsive hydrogel formed by phenylboronic acid grafted to chitosan (PBA-CS), the efficiency of the controlled peptide release has increased approximately by a factor of 2.6. The hydration ratio of such hydrogel is significantly lower in acidic environments than in neutral and basic media, which has been attributed to the dissociation of the boronate bonds between polymer chains. Hence, the electro-controlled peptide release from PBA-CS/CR(NMe)EKA/PEDOT hydrogels, in the acidic environment of tumors, combines the effects of the oxidation and reduction of PEDOT chains on the interactions with the peptide and the carrier, with the peptide concentration gradient at the interface between the collapsed hydrogel and the release medium. Furthermore, the peptide released by electro-stimulation preserved its bioactivity assessed by promoting human prostate cancer cells death. Overall, this work is a promising attempt to develop a carrier platform for small hydrophilic anticancer peptides, which delivery rationale is synergistically regulated by the electrical and pH responsiveness of the carrier., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ulcerative colitis (UC) is a challenging inflammatory gastrointestinal disorder, whose therapies encounter limitations in overcoming insufficient colonic retention and rapid systemic clearance. In this study, we report an innovative polymeric prodrug nanoformulation for targeted UC treatment through sustained 5-aminosalicylic acid (5-ASA) delivery. Amphiphilic polymer-based 13.5 nm micelles were engineered to incorporate azo-linked 5-ASA prodrug motifs, enabling cleavage via colonic azoreductases. In vitro, micelles exhibited excellent stability under gastric/intestinal conditions while demonstrating controlled 5-ASA release over 24 h in colonic fluids. Orally administered micelles revealed prolonged 24-h retention and a high accumulation within inflamed murine colonic tissue. At an approximately 60% dose reduction from those most advanced recent studies, the platform halted DSS colitis progression and outperformed standard 5-ASA therapy through a 77-97% suppression of inflammatory markers. Histological analysis confirmed intact colon morphology and restored barrier protein expression. This integrated prodrug nanoformulation addresses limitations in colon-targeted UC therapy through localized bioactivation and tailored pharmacokinetics, suggesting the potential of nanotechnology-guided precision delivery to transform disease management., (© 2024. The Author(s).)

To improve treatment compliance and reach sustained and controlled drug release in the colon, we developed a hollow mesoporous silica nano-suppository that responded to both pH and redox stimuli. Firstly, we prepared hollow mesoporous silica nanoparticles containing disulfide bonds (HMSN-SS) and loaded them with 5-ASA. Secondly, we modified the surface of HMSN-SS with polydopamine (PDA) and chitosan (CS) and molded the suppository, which we named 5-ASA@HMSN-SS-PDA-CS (5-ASA@HSPC). By administering 5-ASA@HSPC rectally, it acted directly on the affected area. CS helped the nanoparticles adhere to the colon's surface, while PDA dissociates from HMSN-SS due to protonation in the acidic environment of the ulcerative colon. The disulfide bonds were destroyed by the reducing environment of the colon, leading to a stable and slow release of encapsulated 5-ASA from the pores of HMSN. Finally, in vitro release experiments and in vivo pharmacokinetic and pharmacodynamic experiments had demonstrated that 5-ASA@HSPC exhibited a slow and steady action at the colonic site, with an excellent safety profile. This novel approach showed great potential in the treatment of ulcerative colitis., (© 2024. Controlled Release Society.)

Introduction: Quercetin (QUER), a flavonoid abundant in fruits and vegetables, is emerging as a promising alternative therapeutic agent for obesity treatment due to its antioxidant and anti-adipogenic properties. However, the clinical application of QUER is limited by its poor solubility, low bioavailability, and potential toxicity at high doses. To address these challenges, this study aims to develop an advanced drug delivery system using fluorescent mesoporous silica nanoparticles (FMSNs) coated with polydopamine (PDA) for the efficient and sustained delivery of QUER to inhibit adipogenesis., Methods: The research included the synthesis of PDA-coated FMSNs for encapsulation of QUER, characterization of their mesoporous structures, and systematic investigation of the release behavior of QUER. The DPPH assay was used to evaluate the sustained radical scavenging potential. Concentration-dependent effects on 3T3-L1 cell proliferation, cellular uptake and adipogenesis inhibition were investigated., Results: PDA-coated FMSNs exhibited well-aligned mesoporous structures. The DPPH assay confirmed the sustained radical scavenging potential, with FMSNs-QUER@PDA showing 53.92 ± 3.48% inhibition at 72 h, which was higher than FMSNs-QUER (44.66 ± 0.57%) and free QUER (43.37 ± 5.04%). Concentration-dependent effects on 3T3-L1 cells highlighted the enhanced efficacy of PDA-coated FMSNs for cellular uptake, with a 1.5-fold increase compared to uncoated FMSNs. Adipogenesis inhibition was also improved, with relative lipid accumulation of 44.6 ± 4.6%, 37.3 ± 4.6%, and 36.5 ± 7.3% at 2.5, 5, and 10 μM QUER concentrations, respectively., Conclusion: The study successfully developed a tailored drug delivery system, emphasizing sustained QUER release and enhanced therapeutic effects. FMSNs, especially when coated with PDA, exhibit promising properties for efficient QUER delivery, providing a comprehensive approach that integrates advanced drug delivery technology and therapeutic efficacy., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Kim et al.)

Purpose: This study was designed to develop ibuprofen (IBU) sustained-release amorphous solid dispersion (ASD) using polymer composites matrix with drug release plateaus for stable release and to further reveal intrinsic links between polymer' matrix ratios and drug release behaviors., Methods: Hydrophilic polymers and hydrophobic polymers were combined to form different composite matrices in developing IBU ASD formulations by hot melt extrusion technique. The intrinsic links between the mixed polymer matrix ratio and drug dissolution behaviors was deeply clarified from the dissolution curves of hydrophilic polymers and swelling curves of composite matrices, and intermolecular forces among the components in ASDs., Results: IBU + ammonio methacrylate copolymer type B (RSPO) + poly(1-vinylpyrrolidone-co-vinyl acetate) (PVP VA64) physical mixtures presented unstable release behaviors with large error bars due to inhomogeneities at the micrometer level. However, IBU-RSPO-PVP VA64 ASDs showed a "dissolution plateau phenomenon", i.e., release behaviors of IBU in ASDs were unaffected by polymer ratios when PVP VA64 content was 35% ~ 50%, which could reduce risks of variations in release behaviors due to fluctuations in prescriptions/processes. The release of IBU in ASDs was simultaneously regulated by the PVP VA64-mediated "dissolution" and RSPO-PVP VA64 assembly-mediated "swelling". Radial distribution function suggested that similar intermolecular forces between RSPO and PVP VA64 were key mechanisms for the "dissolution plateau phenomenon" in ASDs at 35% ~ 50% of PVP VA64., Conclusions: This study provided ideas for developing ASD sustained-release formulations with stable release plateau modulated by polymer combinations, taking full advantages of simple process/prescription, ease of scale-up and favorable release behavior of ASD formulations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

An interpenetrating polymer network (IPN) of areca cellulose and guar gum grafted with poly (N, N'-dimethylacrylamide) was made by microwave irradiation technique. N, N-methylenebisacrylamide (MBA) was used as the crosslinking agent. The network polymer was characterised using Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA), Powder X-ray Diffraction (XRD) and Field Emission Scanning Electron Microscopy (FESEM). The chemical interaction between the drug and the polymer was studied using Differential Scanning Calorimetry (DSC). The swelling of the gel was measured under different pH conditions and the swelling parameters were evaluated. The gel was loaded with an anti-diabetic drug, Metformin Hydrochloride, and the in vitro drug release was studied in gastric and intestinal conditions. The results indicated complete release of the drug in 6 h under pH 1.2 and in 10 h under pH 7.4. The kinetic analysis of release data indicated the drug release to follow Higuchi's model. The release exponent "n" of Korsmeyer-Peppas model was found to be >0.45 indicating the drug diffusion to be a non-Fickian process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The objective of this study is to clarify the mechanism of extending release of highly water-soluble drugs via counter polymer (CP) utilization in poly(ethylene oxide) (PEO)/polyethylene glycol (PEG) matrix tablets. Carbomer, poly(acrylic acid), was used as a CP, which has the opposite charges to the drugs. The in vitro release of several highly water-soluble drugs from PEO/PEG tablet with or without CP were tested, the relationship between the sustained release effect by a CP (SRE) and the physicochemical properties of the drugs was investigated. The results demonstrated that the utilization of CP can extend the release of some highly water-soluble drugs by effectively controlling the drug diffusion through matrices. On the other hand, the effectiveness of CP was different depending on the drugs applied. There were not statistical correlations between SRE and physicochemical properties such as solubility, molecular weight, and charge intensity of the drugs, while a micelle forming property of the drugs played an important role in SRE by CP. It was concluded that CP, Carbomer, having negative charges could effectively interact with opposite charges on the surface of stable drug micelles, which could result in a significant decrease in drug diffusion leading to extended drug release. It is considered that the system utilizing CP is a promising approach to achieve extended release of highly water-soluble drugs with a reasonable tablet size, especially in the case of large drug loading.

Composite hydrogels of Na-Alginate (Na-ALG) and Gelatin (GEL) with conducting polymers (CPs) were synthesised using poly(o-phenylenediamine) (POPD), polyaniline (PANI), poly(1-naphthylamine (PNA) and poly(vinylenedine fluoride) (PVDF). The synthesised hydrogels were characterized using FTIR, scanning electron microscopy (SEM) rheology, swelling ability and in-vitro drug release characteristics. The purpose of this investigation was to determine whether these hydrogels could be used to deliver antibiotics for extended drug release. The composite hydrogels were loaded with antibiotic drug: amoxicillin in three different concentrations and the release was studied at intestinal fluid (pH 7.4) and gastric fluid (pH 1.2). Release kinetics was found to show best fit in zero order models at both pH values and showed prolonged release characteristics. The POPD-Na-ALG/GEL showed highest release at intestinal pH of 7.4, while PVDF-Na-ALG/GEL showed highest release at gastric pH at 1.2., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In the present study, novel gastroretentive bilayer tablets were developed that are promising for the once-a-day oral delivery of the drug candidate MT-1207. The gastroretentive layer consisted of a combination of hydrophilic and hydrophobic polymers, namely polyethylene oxide and Kollidon ® SR. A factorial experiment was conducted, and the results revealed a non-effervescent gastroretentive layer that, unlike most gastroretentive layers reported in the literature, was easy to prepare, and provided immediate tablet buoyancy (mean floating lag time of 1.5 s) that lasted over 24 h in fasted state simulated gastric fluid (FaSSGF) pH 1.6, irrespective of the drug layer, thereby allowing a 24-hour sustained release of MT-1207 from the drug layer of the tablets. Furthermore, during in vitro buoyancy testing of the optimised bilayer tablets in media of different pH values (1.0, 3.0, 6.0), the significant difference (one-way ANOVA, p  < 0.001) between the respective total floating times indicated that stomach pH effects on tablet buoyancy are important to be considered during the development of non-effervescent gastroretentive formulations and the choice of dosing regimen. To the best of our knowledge, this has not been reported before, and it should probably be factored in when designing dosing regimens. Finally, a pharmacokinetic study in Beagle dogs indicated a successful in vivo 24-hour sustained release of MT-1207 from the optimised gastroretentive bilayer tablet formulations with the drug plasma concentration remaining above the estimated minimum effective concentration of 1 ng/mL at the 24-hour timepoint and also demonstrated the gastroretentive capabilities of the hydrophilic and hydrophobic polymer combination. The optimised formulations will be forwarded to clinical development.

Purpose: This work aimed to fabricate alginate based in-situ gelling matrix of vildagliptin improved by calcium and carboxy methyl cellulose (CMC) for appropriate adjustment of the onset and duration of action. This easy-to-swallow thickened liquid preparation aimed to improve compliance for dysphagic or elderly diabetic patients., Methods: Vildagliptin dispersions containing alginate were fabricated in the presence or absence of calcium chloride to assess the effect of calcium ion, then a matrix containing 1.5% w/v of sodium alginate with calcium was further examined after the addition of CMC with different concentrations ranging from 0.1% to 0.3%. The viscosity, gelling forming property, Differential scanning calorimetry, and in-vitro drug release were assessed before monitoring the hypoglycemic effect of the selected formulation., Results: In-situ gel matrixes were fabricated at gastric pH with and without calcium ions. The best formula concerning viscosity and the gel-forming property was achieved with higher CMC concentrations, which in turn decreased the rate of vildagliptin release in stimulated gastric pH. In-vivo results confirmed the extended hypoglycemic effect of the vildagliptin in-situ gelling matrix compared to the vildagliptin aqueous solution., Conclusion: This study represents a green polymeric-based in-situ gel as a liquid oral retarded release preparation intended for reducing dose frequency, easier administration of vildagliptin, and improving compliance in geriatric and dysphagic diabetic patients.

The polymeric cytisine-enriched fibers based on poly(3-hydroxybutyrate) were obtained using electrospinning method. The biocompatibility study, advanced thermal analysis and release of cytisine from the poly(3-hydroxybutyrate) fibers were carried out. The nanofibers' morphology was evaluated by scanning electron microscopy. The formation and description of phases during the thermal processes of fibers by the advanced thermal analysis were examined. The new quantitative thermal analysis of polymeric fibers with cytisine phases based on vibrational, solid and liquid heat capacities was presented. The apparent heat capacity of fibers was measured using the standard differential scanning calorimetry. The quantitative analysis allowed for the study of the glass transition and melting/crystallization process. The mobile amorphous fraction, degree of crystallinity and rigid amorphous fraction were determined depending on the thermal history of semicrystalline polymeric fibers. Furthermore, the cytisine dissolution behaviour was studied. It was observed that the kinetic of the release from polymeric nanofiber is delayed than for the marketed product. The immunosafety of the tested polymeric nanofibers with cytisine was confirmed by the Food and Drug Agency Guidance as well as the European Medicines Agency. The polymeric matrix with cytisine seems to be a promising candidate for the prolonged release formulation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Anna Czerniecka-Kubicka reports financial support was provided by National Science Centre, Poland. Vladimir Sedlarik reports financial support was provided by Ministry of Education, Youth and Sports of the Czech Republic., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The aim of this study was to produce sustained-release tablets by V-shaped blending of polymer and tablets without using solvents or heating, and we investigated the design of polymer particles with high coating performance by modifying the structure of the particles using sodium lauryl sulfate. Dry-latex particles of ammonioalkyl methacrylate copolymer were prepared by adding the surfactant into aqueous latex, followed by freeze drying. The resulting dry latex was mixed with tablets (1:10) using a blender and the resulting coated tablets were characterized. Tablet coating by the dry latex was promoted as the weight ratio of surfactant to polymer increased. At a surfactant ratio of 5%, deposition of the dry latex was most effective and the resulting coated tablets (annealed at 60 °C/75%RH for 6 h) exhibited sustained-release characteristics over a period of 2 h. The addition of SLS prevented coagulation of colloidal polymer in the freeze drying, resulting in a loose-structured dry latex. This latex was easily pulverized by V-shaped blending with tablets and the resulting fine particles with high adhesiveness were deposited on the tablets. However, at a surfactant ratio of 10%, the coating of dry latex decreased due to reduced adhesiveness., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Today, polymer systems can be formed to respond to single stimuli or multiple stimuli by changing their properties. The use of these systems, which are designed to be sensitive to stimuli, is expanding in a wide range of applications. Herein, microspheres of sodium alginate (NaAlg) and hydroxypropyl cellulose (HPC) sensitive to dual stimuli for the controlled release of model drug paracetamol were produced by the ionotropic gelation method in the presence of Zn 2+ ions. FTIR, DSC, TGA, SEM, and particle size measurements were used to describe the blend microspheres. Low critical solution temperatures (LCST) of polymer blends at different ratios were determined and the biggest change according to the LCST value of HPC was found to be approximately 1-2 °C lower than 41 °C in microspheres with a NaAlg/HPC ratio of 50/50. In vitro release experiments of paracetamol from microspheres were carried out in a gastrointestinal tract simulation environment at two different temperatures (37 °C and 47 °C). From the release profiles, paracetamol release varied depending on the NaAlg/HPC ratio, the paracetamol content in the microspheres, the exposure time to Zn 2+ ions, and the pH of the medium. Among the microsphere formulations, the highest entrapment efficiency was 57.86%, obtained for B 7 formulation microspheres with a NaAlg/HPC ratio of 70/30, a paracetamol loading percentage of 20%, and a crosslinking time of 5 min.RESEARCH HIGHLIGHTSMicrospheres of sodium alginate (NaAlg) and hydroxypropyl cellulose (HPC) sensitive to dual stimuli for the controlled release of model drug paracetamol were produced by the ionotropic gelation method in the presence of Zn 2+ ions.LCST values of the microspheres with a NaAlg/HPC ratio of 50/50 were significantly lower by 1-2 °C than the LCST value of HPC, and the release results supported the temperature sensitivity of the microspheres.Among the microsphere formulations, the highest entrapment efficiency was 57.86% obtained for B 7 formulation microspheres.These microspheres can be used as a temperature-sensitive drug delivery system in the biomedical field and also as an encapsulation system of cancer drugs for cancer treatment modalities such as hyperthermia.

Pharmaceutical dosage forms such as tablets and capsules are often coated with a functional polymer to modify the drug release. To obtain the drug release profiles, ensure quality control and predict in-vivo performance, dissolution studies are performed. However, dissolution tests are time-consuming, sample destructive and do not readily allow for at-line or in-line characterization. Rapid assessment of functional coatings is essential for products where a single capsule is comprised of hundreds of functionally-coated pellets and the collective drug release kinetics of the entire capsule depends on contributions from each pellet. Here, single Raman measurements were used to evaluate the coating thickness distributions of a dosage form comprised of small, functionally-coated pellets in capsules. First, the composition and physicochemical properties of pellets were characterized by multivariate analysis assisted Raman mapping of pellet cross-sections. Second, a method of collecting single Raman spectrum with spectral contributions from the coating and API layers was developed and optimized to estimate the thickness of coatings. The coating thicknesses obtained from single Raman measurements of pellets in each capsule revealed thickness distributions that correlated with the dissolution profiles (capsules with one distribution had single stage release and capsules with two distributions had a two-stage release). Finally, an unsupervised multivariate analysis method was demonstrated as a rapid and efficient way to correlate dissolution profiles of enterically coated pellets. In summary, this study presents a non-destructive and rapid characterization method for assessing coating thickness and has the potential to be applied in process analytical technologies to ensure coating uniformity and predict product dissolution rate performance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

All-aqueous, surfactant-free, and pH-driven nanoformulation methods to generate pH- and temperature-responsive polymer nanoparticles (NPs) are described. Copolymers comprising a poly(methyl methacrylate) (PMMA) backbone with a few units of 2-(dimethylamino)ethyl methacrylate (DMAEMA) are solubilized in acidic buffer (pH 2.0) to produce pH-sensitive NPs. Copolymers of different molar mass (2.3-11.5 kg mol -1 ) and DMAEMA composition (7.3-14.2 mol%) are evaluated using a "conventional" pH-driven nanoformulation method (i.e., adding an aqueous polymer solution (acidic buffer) into an aqueous non-solvent (basic buffer)) and a robotized method for pH adjustment of polymer dispersions. Dynamic light scattering, zeta-potential (ζ), and sedimentation-diffusion analyses suggest the formation of dual-responsive NPs of tunable size (from 20 to 110 nm) being stable for at least 28 days in the pH and temperature intervals from 2.0 to 6.0 and 25 to 50 °C, respectively. Ultraviolet-visible spectroscopic experiments show that these NPs can act as nanocarriers for the pH-sensitive dipyridamole drug, expanding its bioavailability and potential controlled release as a function of pH and temperature. These approaches offer alternative strategies to prepare stimuli-responsive NPs, avoiding the use of harmful solvents and complex purification steps, and improving the availability of biocompatible polymer nanoformulations for specific controlled release of pH-sensitive cargos., (© 2022 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.)

Low methoxy pectin (LM pectin) suffers from burst release owing to its high swellability and solubility in water. Consequently, in ways to design an ideal drug delivery system, these obstacles must be surmounted. Therefore, the work aimed to design dual crosslinked LM pectin -neem gum (NG) mediated interpenetrating polymer network (IPN) floating mucoadhesive microbeads for lansoprazole (LNZ) gastro-retentive delivery. In short, LNZ-loaded floating microbeads were achieved by using the ionic gelation method wherein zinc acetate was preferred as a crosslinking agent. The optimization of IPN microbeads was performed employing a 3 2 factorial design wherein concentration of pectin and NG was considered as independent factors whereas dependant factors are entrapment efficiency and drug release. Importantly, carboxylic functionality of low methoxy (LM) pectin and hydroxylic functionality NG cross-linked with Zn +2 forms a 3D network. Diffractogram and thermogram revealed that conversion of drug from crystalline to amorphous form because of entrapment of drug within polymeric network. Anticipated floating microbeads showed that polymer concentration had considerable effect on drug encapsulation efficiency and drug release. Briefly, optimizing floating microbeads (Batch B:5) showed maximum drug entrapment (87.47 %) with a delayed drug release (69.20 %, at 8 h) due to formation of strong IPN. Moreover, it showed good mucoadhesive aptitude with goat stomach mucosa because of entanglement between gum and mucus layer. In addition, use of calcium silicate assists to modulate floating profile of IPN microbeads. Therefore, designing dual crosslinked zinc-pectinate-NG mediated IPN floating mucoadhesive microbeads will offer a new substitute for floating delivery., Competing Interests: Declaration of competing interest There was no conflict of interest disclosed by the authors., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The objective of this study was to explore an innovative sustained release technology and design a new microporous resin-based polymer device (RPD) for controlled release of glipizide (GZ). Photocurable resin was applied to prepare the resin layer to control GZ release. The impact of formulation parameters consisting of the type and amount of pore formers and pH modifiers, photocurable curing time as well as the weight of resin layer on GZ release were examined. The GZ-RPD was fabricated applying 24 mg of resin layer with PEG400 (100 % of the resin weight) as pore former and 10 mg of Na 2 CO 3 as pH modifier. Scanning electron microscopy (SEM) demonstrated resin particles presenting a porous structure constituted the resin layer. The GZ-RPD possessed prolonged T max and reduced C max relative to commercial tablets. The relative bioavailability of the RPDs as well as commercial tablets was 93.65 % since the AUC 0-24 h were 6111.05 ± 238.89 ng·h/mL and 6525.09 ± 760.59 ng h/mL, respectively. The release mechanism of the GZ-RPD was discussed. This paper provided an innovative concept to produce controlled GZ release oral formulation fabricated by photocurable resin, which demonstrated both excellent in vitro release and in vivo pharmacokinetics., Competing Interests: Conflict of interest statement The authors declare that there are no conflicts of interest., (Copyright © 2022. Published by Elsevier Masson SAS.)

This study aims to evaluate the feasibility of producing acyclovir-containing modified release matrix tablets by a wet granulation method based on the type and concentration of two pharmaceutical-grade hydrophilic matrix polymers (i.e., hydroxypropyl methylcellulose (HPMC), carbomers, and their combinations) commonly used in biomedical applications. The mechanical properties of the tablets and in vitro and in vivo performance were studied. The physicochemical properties of the raw materials and corresponding physical mixtures were characterized by differential scanning calorimetry, showing that the hydrophilic polymers did not influence the physicochemical properties of the drug. The wet granulation process improved the flow and compression properties of the obtained granules. This method enabled the preparation of the matrix tablets of acyclovir with appropriate mechanical properties concerning hardness and friability. The drug release kinetics was governed by the type and concentration of the hydrophilic polymers composing the matrices. The study has proven that HPMC-composed tablets were superior in modified drug release properties compared to carbomer- and HPMC/carbomer-based tablets. Mathematical analysis of the release profiles, determined in a medium adjusted to pH 1.2 followed by pH 7.4, revealed that the drug released from the hydrophilic tablets followed non-Fickian first-order kinetics. An optimal HPMC-based formulation submitted to accelerated stability studies (40 °C, 75% RH) was stable for three months. A complete cross-over bioavailability study of the selected acyclovir-loaded sustained release tablets and marketed immediate-release tablets were compared in six healthy male volunteers. The extent of drug absorption from the sustained release tablets was significantly greater than that from immediate-release pills, which may improve the drug's antiviral properties attributed to the lower elimination rate and enhanced acyclovir half-life.

In the current study, a novel interpenetrating polymer network (IPN) hydrogel bead was developed by encapsulation of antidiabetic drug glipizide using sodium alginate (SAL) and xanthan gum (XAG) biopolymers by ionotropic gelation technique with calcium chloride as cross-linking agent. In light of the fact that IPN hydrogel beads possess greater benefits in controlling the release of such short acting drug, sodium alginate and xanthan gum IPN hydrogel beads were prepared at different mass ratios (SAL:XAG = 10:0, 9:1, 8:2, 7:3, 6:4, 5:5). Similarly, drug-loaded IPN hydrogel beads were also developed. The prepared hydrogel beads were investigated using Fourier transform infrared spectroscopy, X-ray powder diffraction, and thermogravimetric studies to understand the type of interactions between the composite beads. Surface morphology changes were studied by scanning electron microscopy. The particle size, drug entrapment efficiency, and swelling behavior of prepared hydrogel beads were also studied. Based on in vitro drug dissolution studies, it was observed that SXF4 preparation containing SAL and XAG polymers at 7:3 ratio showed extended drug release of 97.53% at 9 h. This study demonstrated that inclusion of XAG has extended the drug release and able to achieve zero-order drug release profile.

For effective resolution of regional subacute inflammation and prevention of biofouling formation, we have developed a polymeric implant that can release meloxicam, a selective cyclooxygenase (COX)-2 inhibitor, in a sustained manner. Meloxicam-loaded polymer matrices were produced by hot-melt extrusion, with commercially available biocompatible polymers, poly(ε-caprolactone) (PCL), poly(lactide-co-glycolide) (PLGA), and poly(ethylene vinyl acetate) (EVA). PLGA and EVA had a limited control over the drug release rate partly due to the acidic microenvironment and hydrophobicity, respectively. PCL allowed for sustained release of meloxicam over two weeks and was used as a carrier of meloxicam. Solid-state and image analyses indicated that the PCL matrices encapsulated meloxicam in crystalline clusters, which dissolved in aqueous medium and generated pores for subsequent drug release. The subcutaneously implanted meloxicam-loaded PCL matrices in rats showed pharmacokinetic profiles consistent with their in vitro release kinetics, where higher drug loading led to faster drug release. This study finds that the choice of polymer platform is crucial to continuous release of meloxicam and the drug release rate can be controlled by the amount of drug loaded in the polymer matrices., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Cell-penetrating poly(disulfide)s (CPDs) are promising vehicles for cytosolic delivery of proteins. However, currently available arginine-rich CPD has rarely been reported for systemic delivery due to its "always" positive charge. Herein, we developed pH-responsive CPD IMD that executes tumor targeting delivery via protonation of imidazole groups within the acidic tumor microenvironment.

Monoclonal antibodies (mAbs) are large size molecules that have demonstrated high therapeutic potential for the treatment of cancer or autoimmune diseases. Despite some excellent results, their intravenous administration results in high plasma concentration. This triggers off-target effects and sometimes poor targeted tissue distribution. To circumvent this issue, we investigated a local controlled-delivery approach using an in situ forming depot technology. Two clinically relevant mAbs, rituximab (RTX) and daratumumab (DARA), were formulated using an injectable technology based on biodegradable PEG-PLA copolymers. The stability and controlled release features of the formulations were investigated. HPLC and mass spectrometry revealed the preservation of the protein structure. In vitro binding of formulated antibodies to their target antigens and to their cellular FcγRIIIa natural killer cell receptor was fully maintained. Furthermore, encapsulated RTX was as efficient as classical intravenous RTX treatment to inhibit the in vivo tumor growth of malignant human B cells in immunodeficient NSG mice. Finally, the intra-articular administration of the formulated mAbs yielded a sustained local release associated with a lower plasma concentration compared to the intra-articular delivery of non-encapsulated mAbs. Our results demonstrate that the utilization of this polymeric technology is a reliable alternative for the local delivery of fully functional clinically relevant mAbs., (Copyright © 2021. Published by Elsevier B.V.)

Trimesic acid (TMA) and ethyelene diamine (ED) were reacted in various molar proportions to yield several branched/hyperbranched copolymers which formed polymersome-like structures, and they were used for encapsulation and release of a model drug, α-tocopherol succinate (TOS). The branched topology of the copolymers was established from spectroscopy, viscometry, and rheological measurements. Hydrodynamic size and transmission electron microscopy revealed the self-aggregated polymersome-like features of the copolymers with a dense core. Zeta potential studies unveiled pH-sensitive features of the aggregates. Both hydrodynamic size and viscosity were found to decrease with more branching, whereas the encapsulation efficiency displayed a drastic increase from 68 to 89.5% from the least branched (30%) to mostly branched grade (68%). The hydrophobic drug was primarily accommodated within the macromolecular voids inside the core and was released slowly following the diffusion mechanism. An indigenous model was established to explain the release kinetics from such a pH-sensitive and highly branched core-shell matrix which yielded a unique parameter called effective diffusivity or ED that took account of those parameters affecting the release rate. The copolymers were found to be biologically viable through a series of in vitro tests, thus inviting in vivo trials for future experimentation.

Supramolecular hydrogels are 3D, elastic, water-swelled materials that are held together by reversible, non-covalent interactions, such as hydrogen bonds, hydrophobic, ionic, host-guest interactions, and metal-ligand coordination. These interactions determine the hydrogels' unique properties: mechanical strength; stretchability; injectability; ability to self-heal; shear-thinning; and sensitivity to stimuli, e.g., pH, temperature, the presence of ions, and other chemical substances. For this reason, supramolecular hydrogels have attracted considerable attention as carriers for active substance delivery systems. In this paper, we focused on the various types of non-covalent interactions. The hydrogen bonds, hydrophobic, ionic, coordination, and host-guest interactions between hydrogel components have been described. We also provided an overview of the recent studies on supramolecular hydrogel applications, such as cancer therapy, anti-inflammatory gels, antimicrobial activity, controlled gene drug delivery, and tissue engineering.

Exenatide is a small therapeutic peptide being currently used in clinic for the treatment of diabetes mellitus type II, however, displaying a short blood circulation time which makes two daily injections necessary. Covalent polymer modification of a protein is a well-known approach to overcome this limitation, resulting in steric shielding, an increased size and therefore a longer circulation half-life. In this study, we employed site-selective C-terminal polymer ligation of exenatide via copper-catalyzed azide-alkyne-cycloaddition (CuAAC) to yield 1:1-conjugates of either poly(ethylene glycol) (PEG) or linear polyglycerol (LPG) of different molecular weights. Our goal was to compare the impact of the two polymers on size, structure and activity of exenatide on the in vitro and in vivo level. Both polymers did not alter the secondary structure of exenatide and expectedly increased its hydrodynamic size, where the LPG-versions of exenatide showed slightly smaller values than their PEG-analogs of same molecular weight. Upon conjugation, GLP-1 receptor activation was diminished, however, still enabled maximum receptor response at slightly higher concentrations. Exenatide modified with a 40 kDa LPG (Ex-40-LPG) showed significant reduction of the blood glucose level in diabetic mice for up to 72 h, which was comparable to its PEG-analog, but 9-fold longer than native exenatide (8 h)., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The objective of this work was to investigate the influence of tablet location along the bottom of a USP apparatus II vessel on polymer erosion and drug release of surface-erodible sustained-release tablets using computational simulation methods. Computational fluid dynamics (CFD) methods were performed to simulate the velocity distribution. A mathematical model was developed to describe polymer erosion and tablet deformation according to the mass transfer coefficient. Numerical analysis was used to simulate drug release controlled by drug diffusion and polymer erosion. The results indicated that tablets located at the off-center position deformed faster than the tablets located at the center position. However, tablet location had no profound impact on drug release rate since all drug release profiles were "similar" according to the f 2 similarity values which were above 50. Hence, our simulation supported that the USP apparatus II was a reliable and robust device for the dissolution testing of surface-erodible sustained-release tablets.

A reversible switchable on-demand UV-triggered drug delivery system (DDS) based on interpenetrating polymer networks (IPNs) with silicone as the host polymer and spiropyran (SP)-functionalized guest polymer is designed and demonstrated. The photo-responsive IPNs provide a new triggered drug delivery concept as they exploit the change in intermolecular interactions (work of adhesion) among the drug, matrix, and solvent when the incorporated hydrophobic SP moieties transform into the hydrophilic merocyanine form upon light irradiation without degradation and disruption of the DDS. The change in how the copolymer composition (hydrophilicity and content) and the lipophilicity of the drug (log P ) affect the release profile was investigated. A thermodynamic model, based on Hansen solubility parameters, was developed to design and optimize the polymer composition of the IPNs to obtain the most efficient light-triggered drug release and suppression of the premature release. The developed IPNs showed excellent result for dopamine, l-dopa, and prednisone with around 90-95% light-triggered release. The model was applied to study the release behavior of drugs with different log P and to estimate if the light-induced hydrophobic-to-hydrophilic switch can overcome the work of adhesion between polymers and drugs and hence the desorption and release of the drugs. To the best of our knowledge, this is the first time that work of adhesion is used for this aim. Comparing the result obtained from the model and experiment shows that the model is useful for evaluating and estimating the release behavior of specific drugs merocyanine, IPN, DDS, and spiropyran.

Dimethyl disulfide (DMDS), a promising alternative fumigant, has been highly desirable for excellent management of soil pests and diseases. However, high volatility and moderate toxicity of this sulfide limit its application. To address these issues, a novel controlled release formulation of DMDS was proposed employing multiple emulsions and polyurea microcapsules (DMDS@MEs-MCs). The successful combination of the two technologies was revealed by confocal laser scanning microscopy, scanning electron microscopy, thermogravimetric analysis, and Fourier transform infrared. According to the multiple encapsulation structure, the encapsulation efficiency decreased by only 3.13% after thermal storage, compared with a 15.21% decrease of microcapsules made with only a monolayer film. DMDS@MEs-MCs could effectively control the release of active ingredient, which increased applicator and environmental safety during application. Moreover, it could be facilely used by spraying and drip irrigation instead of a special fumigation device. The innovative formulation exhibited better control efficacy on soil pathogens ( Fusarium spp. and Phytophthora spp.) and root-knot nematodes ( Meloidogyne spp.) than DMDS technical concentration (DMDS TC). In addition, it did not inhibit seed germination after 10 days when the plastic film was removed from the fumigated soil. This method appears to be of broad interest for the development of safe and handy fumigant application.

Controlled-release formulations (CRFs) have potential applications in modern agriculture, for it can not only prolong the duration of agrochemicals but also alleviate the adverse effect on non-target organism. In this study, we constructed pyraclostrobin@SiO 2 @polydopamine microcapsule (Pyr@SiO 2 @PDA MC). The resulting microcapsule is a near-rod shape (about 1.15 μm), which has a drug-loading efficiency of 55%. Fourier transform infrared (FTIR) and thermogravimetric analysis (TG) revealed the successful entrapment of the pesticide. The coating of polydopamine (PDA) endowing the microcapsule with superior UV-shielding properties than pyraclostrobin@SiO 2 microcapsule (Pyr@SiO 2 MC). Compared with pyraclostrobin emulsifiable concentrate (EC), the Pyr@SiO 2 @PDA MC exhibited 9.07-, 5.50-, 4.93- and 4.16-fold higher fungicidal activity against Rice blast fungus ( Pyricularia oryzae) at concentrations of 0.5, 1, 2 and 4 mg/L. Moreover, acute toxicity tests demonstrated that the sample on zebrafish with lower toxicity on the first day. These results showed that the obtained microcapsule may process broader application potential in agriculture.

The development of intelligent and multifunctional hydrogels having photothermal properties, good mechanical properties, sustained drug release abilities with low burst release, antibacterial properties, and biocompatibility is highly desirable in the biomaterial field. Herein, mesoporous polydopamine (MPDA) nanoparticles wrapped with graphene oxide (GO) were physically cross-linked in cellulose nanofibril (CNF) hydrogel to obtain a novel MPDA@GO/CNF composite hydrogel for controllable drug release. MPDA nanoparticles exhibited a high drug loading ratio (up to 35 wt %) for tetracycline hydrochloride (TH). GO was used to encapsulate MPDA nanoparticles for extending the drug release time and reinforcing the physical strength of the obtained hydrogel. The mechanical strength of the as-fabricated MPDA@GO/CNF composite hydrogel was five times greater compared to that of the pure CNF hydrogel. Drug release experiments demonstrated that burst release behavior was significantly reduced by adding MPDA@GO. The drug release time of the MPDA@GO/CNF composite hydrogel was 3 times and 7.2 times longer than that of the polydopamine/CNF hydrogel and pure CNF hydrogel, respectively. The sustained and controlled drug release behaviors of the composite hydrogel were highly dependent on the proportion of MPDA and GO. Moreover, the rate of drug release could be accelerated by near-infrared (NIR) light irradiation and pH value change. The drug release kinetics of the as-prepared composite hydrogel was well described by the Korsmeyer-Peppas model, and the drug release mechanism of TH from the composite hydrogel was anomalous transport. Importantly, this carefully designed MPDA@GO/CNF composite hydrogel showed good biocompatibility through an in vitro cytotoxicity test. In particular, the toxicity of GO was well shielded by the CNF hydrogel. Therefore, this novel MPDA@GO/CNF composite hydrogel with an encapsulation structure for controllable drug release and toxicity shielding of GO could be used as a very promising controlled drug delivery carrier, which may have potential applications for chemical and physical therapies.

Targeted drug delivery systems are a very convenient method of treating inflammatory bowel disease. The properties of pectin make this biopolymer a suitable drug carrier. These properties allow pectin to overcome the diverse environment of the digestive tract and deliver the drug to the large intestine. This investigation proposed bipolymeric formulations consisting of the natural polymer pectin and a synthetic polymer containing the drug 5-aminosalicylic acid. Pectin beads were prepared via ionotropic gelation involving the interaction between the hydrophilic gel and calcium ions. The obtained formulations consisted of natural polymer, 5-aminosalicylic acid (5-ASA) and one of the synthetic polymers, such as polyacrylic acid, polyvinylpyrrolidone, polyethylene glycol or aristoflex. The release of the drug was carried out employing a basket apparatus (USP 1). The acceptor fluid was pH = 7.4 buffer with added enzyme pectinase to reflect the colon environment. The amount of the released drug was determined using UV-Vis spectrophotometry at a wavelength of λ = 330 nm. The kinetics of the drug dissolution revealed that none of the employed models was appropriate to describe the release process. A kinetic analysis of the release profile during two release stages was carried out. The fastest drug release occurred during the first stage from a formulation containing pectin and polyethylene glycol. However, according to the applied kinetic models, the dissolution of 5-ASA was rather high in the formulation without the synthetic polymer during the second stage. Depending on the formulation, 68-77% of 5-ASA was released in an 8-hour time period. The FTIR and DSC results showed that there was no interaction between the drug and the polymers, but interactions between pectin and synthetic polymers were found.

Polymeric nano-carriers have been developed as a most capable and feasible technology platform for gene therapy. As vehicles, polymeric nano-carriers are obliged to possess high gene loading capability, low immunogenicity, safety, and the ability to transfer various genetic materials into specific sites of target cells to express therapeutic proteins or block a process of gene expression. To this end, various types of polymeric nano-carriers have been prepared to release genes in response to stimuli such as pH, redox, enzymes, light and temperature. These stimulus-responsive nano-carriers exhibit high gene transfection efficiency and low cytotoxicity. In particular, dual- and multi-stimulus-responsive polymeric nano-carriers can respond to a combination of signals. Markedly, these combined responses take place either simultaneously or in a sequential manner. These dual-stimulus-responsive polymeric nano-carriers can control gene delivery with high gene transfection both in vitro and in vivo. In this review paper, we highlight the recent exciting developments in stimulus-responsive polymeric nano-carriers for gene delivery applications.

Copolymers synthesized from acrylic acid and methacrylic acid used as gastroprotective and mucoadhesive enteric coatings have been used to prepare micro- (∼2 μm), submicro- (∼200 nm), and nanoparticles (∼20 nm) containing rifampicin (Rif) to obtain time-controlled drug release kinetics. Different particle sizes and drug release kinetics have been obtained using different synthesis conditions and fabrication techniques including the use of an electrosprayer and an interdigital microfabricated micromixer. The antimicrobial action of the encapsulated Rif has been demonstrated against Staphylococcus aureus ATCC 25923 and compared with the effect of the equivalent dose of the free macrolide antibiotic. At low concentrations, the encapsulated antibiotic showed superior antimicrobial activity than the free drug. The stability of the developed particles has been evaluated in vitro under simulated gastric and intestinal conditions. At the concentrations tested, a reduced cytotoxicity against different human cell lines was observed after analyzing their subcytotoxic doses and the influence on their cell cycle by flow cytometry. Drug release kinetics can be tuned by adjusting particle sizes, and it would be possible to reach the minimum inhibitory concentration or the minimum bactericidal concentration at different time points depending on the medical needs.

Releasing a protein according to a zero-order profile without protein denaturation during the polymeric microparticle degradation process is very challenging. The aim of the current study was to develop protein-loaded microspheres with new PLGA based penta-block copolymers for a linear sustained protein release. Lysozyme was chosen as model protein and 40 µm microspheres were prepared using the solid-in-oil-in-water solvent extraction/evaporation process. Two types of PLGA-P188-PLGA penta-block copolymers were synthetized with two PLGA-segments molecular weight (20 kDa or 40 kDa). The resulting microspheres (50P20-MS and 50P40-MS) had the same size, an encapsulation efficiency around 50-60% but different porosities. Their protein release profiles were complementary: linear but non complete for 50P40-MS, non linear but complete for 50P20-MS. Two strategies, polymer blending and microsphere mixing, were considered to match the release to the desired profile. The (1:1) microsphere mixture was successful. It induced a bi-phasic release with a moderate initial burst (around 13%) followed by a nearly complete linear release for 8 weeks. This study highlighted the potential of this penta-block polymer where the PEO block mass ratio influence clearly the Tg and consequently the microsphere structure and the release behavior at 37 °C. The (1:1) mixture was a starting point but could be finely tuned to control the protein release., Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Currently, implantable fibrous medical devices still suffer from invisibility under current clinical imaging techniques. To address this problem, 2, 3, 5-triiodobenzoic acid (TIBA) was recruited as a contrast agent, and then a set of iodinated poly( p -dioxanone) (PPDO) fibers was fabricated via melt-spinning hybrid blends of PPDO with TIBA (PPDO/TIBA). The impact of TIBA content on the rheological behavior of blends was evaluated firstly. The physical, chemical, and thermal properties of PPDO/TIBA fibers were investigated accordingly by SEM, FTIR, DSC, and TGA. Moreover, the radiopaque property of PPDO/TIBA hybrid fibers as a potential radio-opacifying platform for medical devices was verified in vitro and in vivo. Finally, the accumulated release results of the hybrid fibers during in vitro degradation indicate the continual X-ray visibility of the hybrid fibers maintains for 22 days. This intriguing iodinated platform may pave the way for constructing fibrous materials with in-situ X-ray tracking property.

Recently, the application of natural biocompatible polymeric hydrogels for the conception of drug delivery matrices has attracted widespread interest. Thus, in the present study, riboflavin pH-sensitive drug delivery hydrogels were developed based on blue crab chitosan (Cs), via direct dissolution in alkali/urea aqueous solution at low temperatures. First, the effect of Cs characteristics in terms of acetylation degree (AD) and molecular weight (Mw) on the structural, mechanical, thermal, swelling and in vitro biodegradation of Cs-based hydrogels were studied. Data from overall analysis revealed that Cs with low AD and high Mw exhibited improved mechanical properties, as evidenced by the compressive and rheological behaviors tests, thermal resistance, swelling behavior and in vitro degradation kinetics. However, hydrogels pore sizes were reduced with the AD decrease and Mw increase. Additionally, hydrogels in PBS (pH 5.5) underwent quicker degradation, compared to those immersed in PBS (pH 7.4). In the drug delivery model, the kinetics of Riboflavin release, through the Cs-based hydrogels were monitored. The Riboflavin release exhibited typical deliverance patterns, with significantly higher released amounts in more acidic systems. Therefore, drug encapsulation within the conceived pH-sensitive Cs-based hydrogels could provide suitable and promoting microenvironment for drugs delivery., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Floating gastro-retentive delivery systems can prolong the gastric residence providing sustained drug release. In this study, we report on self-inflating effervescence-based electrospun nanofiber membranes embedding polyethylene oxide/sodium bicarbonate cast films. In this system, sodium bicarbonate results in an effervescence effect by creating carbon dioxide gas upon contacting an acidic gastric fluid, with the resulting gas bubbles being entrapped within the swollen network of nanofibers. Eudragit RL and RS polymers are utilized as a host material to manipulate release kinetics of incorporated drugs. Pramipexole, a common medication for chronic Parkinson's disease (PD), is used as a model drug. Uniform and bead-free nanofibers with diameters of ~300 nm were obtained. Although floating nanofibers initially exhibited high water contact angles (WCA), water droplets were quickly absorbed into the surface and the WCA decreased to ~0° within 60 s. Floating lag time, total floating time, swelling properties and drug release profiles were investigated both in a simulated gastric fluid (pH 1.2 buffer solution) and in a simulated intestinal fluid (pH 6.8 buffer solution) at 37 °C. All floating nanofiber formulations began to float instantly with nearly zero floating lag time and did not sink into the solution even after 24 h. By comparison, the same formulations without sodium bicarbonate cast films could not maintain continuous floating beyond 15 min. The floating nanofiber pouches presented lower initial release of between 20 and 57 %, compared to that of non-floating nanofiber pouches (40-82% within 2 h). Clearly, floating nanofibers reduced the initial burst release and provided sustained drug release. This demonstrates the potential to result in 'once-a-day' oral introduction of drugs that normally must be taken frequently. Effervescence-based floating nanofibers present a novel and promising prototype delivery system for the drug delivery in the upper gastro-intestinal (GI) tract., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Oxidative stress, caused by the overproduction of reactive oxygen species (ROS), is often observed in degenerative and/or metabolic diseases, tumors, and inflamed tissues. Boronic acids are emerging as a unique class of responsive biomaterials targeting ROS because of their reactivity toward H2O2. Herein, we examine the oxidative reactivity of nanoparticles from a boronic acid-installed polycarbonate. The extent of oxidation under different concentrations of H2O2 was tracked by the change in fluorescence intensity of an encapsulated solvatochromic reporter dye, demonstrating their sensitivity to biologically-relevant concentrations of hydrogen peroxide. Oxidation-triggered particle destabilization, however, was shown to be highly dependent on the concentration of the final oxidized polymer product, and was only achieved if it fell below polymer critical micelle concentration. Our results indicate that these nanocarriers serve as an excellent dual pH/H2O2 responsive vehicle for drug delivery.

Membranes were fabricated from a blend of synthetic copolymer (thiourea, phenylhydrazine and formaldehyde) and chitosan to study the metformin drug release profile and its kinetics. The membranes were characterized with elemental, scanning electron microscopy, FTIR and 1 H NMR spectroscopy to identify the empirical formula & weight, surface morphology and functional group changes occurred during the incorporation of chitosan to the copolymer. The swelling behaviour, drug loading efficiency and drug release profile of the membranes were studied using UV-visible spectroscopy. The mechanical properties and in vitro degradation studies were also performed. The reactive sites, better porosity and larger surface area provided by chitosan to the copolymer led to higher drug loading efficiency and controlled drug release profile. Kinetic study revealed swelling and diffusion controlled mechanism for the membranes, which obtained from Ritger-Peppas and Higuchi model. The chitosan and its copolymer membranes were tested for antimicrobial assay using selective gram-positive and gram-negative bacterial and fungal strains. The CS-TPF-drug membranes showed an acceptable control of the growth of all the microbial species compared to CS, CS-drug and the standard metformin drug., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Synthetic DNA-based oligonucleotides are loaded into porous silicon nanoparticles (pSiNPs) and incorporated into nanofibers of poly(lactide-co-glycolide) (PLGA), poly-l-lactic acid (PLA), or polycaprolactone (PCL). The resulting hybrid nanofibers are characterized for their ability to release the functional oligonucleotide payload under physiologic conditions. Under temperature and pH conditions mimicking physiological values, the PLGA-based nanofibers release >80% of their DNA cargo within 5 days, whereas the PLA and PCL-based fibers require 15 days to release >80% of their cargo. The quantity of DNA released scales with the quantity of DNA-loaded pSiNPs embedded in the nanofibers; mass loadings of between 2.4 and 9.1% (based on mass of DNA-pSiNP construct relative to mass of polymer composite) are investigated. When a responsive DNA-based nanodevice (i.e. molecular beacon) is used as a payload, it retains its functionality during the release period, independent of the polymer used for the formation of the nanofibers.

This study aimed to develop a bilayer gastroretentive (GR) tablet containing an insoluble drug and ascertain the potential of using hydrophobic polymers in GR matrix systems. Highly porous tablets were prepared using a camphor-based sublimation technique. After the screening of several commonly used polymers, two types of GR layers, a conventional hydrophilic GR layer and a hydrophobic GR layer, were designed. The optimal drug layer comprising Metolose® 90SH-100SR and dicalcium phosphate provided not only a gradual matrix erosion but also high strength after hydration. Regarding the GR layers, the hydrophobic layer based on Kollidon® SR was superior to the hydrophilic layer made of PEO 7 M in terms of wet strength, implying a higher resistance to mechanical stresses upon water absorption. Also, the excellent tableting properties of Kollidon® SR and the effects of curing in improving its matrix hardness resulted in porous tablets with better mechanical strength. Moreover, good flowability and low cohesion of Kollidon® SR formulation were advantageous in direct compression. In conclusion, novel bilayer GR tablets were successfully developed, indicating the potential for widening the application of GR systems to insoluble drugs. The results also suggested numerous advantages of incorporating Kollidon® SR into the production of GR tablets., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Polymer-drug conjugates are polymers with drug molecules chemically attached to polymer side chains through either a weak (degradable bond) or a dynamic covalent bond. These systems are known as pro-drugs in the inactive form when passing into the blood circulation system. When the prodrug reaches the target organ, tissue or cell, the drug is activated by cleavage of the bond between the drug and polymer, under certain conditions existing in the target organ. The advantages of polymer-drug conjugates compared to other controlled-release carriers and conventional pharmaceutical formulations are the increased drug loading capacity, prolonged in vivo; circulation time, enhanced intercellular uptake, better-controlled release, improved therapeutic efficacy, and enhanced permeability and retention effect. The aim of the present review is the investigation of polymer-drug conjugates bearing anti-cancer drugs. The polymer, through its side chains, is linked to the anti-cancer drugs via; dynamic covalent bonds, such as hydrazone/imine bonds, disulfide bonds, and boronate esters. These dynamic covalent bonds are cleaved in conditions existing only in cancer cells and not in healthy ones. Thus, ensuring the selective release of drug to the targeted tissue, reducing in this way, the frequent side effects of chemotherapy, leading to a more targeted application, despite the nature of the applied polymer, possessing the ability to aim tumors selectively via; incorporation of a relative ligand., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The gold nanoparticles surface was modified by thioglycolic acid ligand and their surface was coated by the chitosan-grafted-poly(N-vinylcaprolactam) (chitosan-g-PNVCL) copolymer. The cisplatin anticancer drug was loaded into the synthesized nanocarriers and its performance was investigated for the treatment of MCF-7 breast cancer cells in vitro. The synthesized nanoparticles were characterized using FTIR, DLS, TEM, SEM, EDX and TGA analysis. The lower critical solution temperature (LCST) of PNVCL/chitosan and PNVCL/chitosan coated gold nanoparticles were found to be 38 and 39 °C, respectively. The cisplatin loading efficiency, cisplatin release from nanoparticles at different temperatures and pH values as well as the pharmacokinetic studies were examined. The maximum cisplatin release from nanoparticles was achieved at T > LCST (42 °C) and pH of 5. The Korsemeyer-Peppas model was best described the cisplatin release from nanoparticles. The maximum MCF cell death was found to be 92% using cisplatin loaded-gold/TGA/chitosan-g-PNVCL nanoparticles under an induction heating system., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Development and utilization of oxygen absorbing materials for food and beverage packaging are important to protect the oxygen-sensitive foods. In this study, we developed a kind of ionic polymer with excellent oxygen absorbing ability based on reacting ethylene-acrylic acid copolymer (EAA) and sodium sulfite (Na 2 SO 3 ). By virtue of the hydrophilicity of the ionic polymer, the sulfite in Na 2 SO 3 is easily hydrolyzed and ionized. The oxygen inhalation reaction was gradually initiated and started, whereas achieved a slow and controllable oxygen absorption process. The oxygen absorbing agent can be directly added in the form of an auxiliary agent, which greatly simplifies the preparation process of the oxygen absorbing material. Furthermore, the ionic structure of the EAA/Na 2 SO 3 composites were destroyed and mechanical properties of the material did not decrease after oxygen absorption. More importantly, it can effectively prevent the entry of external oxygen because the ionic polymer itself has better barrier properties. PRACTICAL APPLICATION: Typical oxygen-sensitive objects include: beer, coffee, canned food, meat products, dairy products, and so on. The presence of oxygen in the package can cause microbial growth, odor generation, color change and nutrient loss, resulting in a significant reduction in food shelf life. Therefore, controlling the oxygen content of the food package is important to limit the rate of these spoilage and spoilage reactions in the food. Materials with active oxygen scavenging and good barrier properties and packaging performance are highly economically viable in terms of improving product quality and reducing packaging costs., (© 2020 Institute of Food Technologists®.)

Metal nanoparticles are well known for their antimicrobial properties. The use of metalbased nanoparticles in the agricultural field has considerably increased globally by both direct and indirect means for the management of plant diseases. In this context, the development of controlled delivery systems for slow and sustained release of metal nanoparticles is crucial for prolonged antimicrobial activity. Polymers have emerged as a valuable carrier for controlled delivery of metal nanoparticles as agrochemicals because of their distinctive properties. The most significant benefits of encapsulating metal nanoparticles in a polymer matrix include the ability to function as a protector of metal nanoparticles and their controlled release with prolonged efficacy. This review focuses on loading strategies and releasing behavior of metal nanoparticles in the polymer matrix as antimicrobial agents for plant diseases. The Polymer-metal nanocomplexes (PMNs) comprise a biocompatible polymeric matrix and metal nanoparticles as active components of an antimicrobial agent, pesticides and plant growth regulators used to enhance the crop productivity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A pH-sensitive polymeric carrier was developed in this study for local delivery of anticancer drug bortezomib (BTZ) to cancer cells. Our strategy is based on the conjugation of BTZ to polymeric carriers containing catechol groups, which are considered to release BTZ selectively in cancer cells. In this study we used alginate-conjugated polydopamine as a building block polymer. The catechol moiety of polydopamine binds to the boronic acid group of BTZ drug and release the drug molecules in a pH-dependent method. Cancer tissue has acidic environment where BTZ dissociate from the catechol group of polydopamine to control the release of the free drug. Mathematical equation models were used to clarify the mechanism of drug release. The release profile fitted first order with correlation coefficient (R 2  = 0.98), the release mechanism was studied using Korsmeyer-Peppas, Higuchi, Hixson-Crowell, and Kopcha models. We revealed the release mechanism follows non-fickian and diffusion was the dominant mechanism while small portion contributed to erosion. The pH-sensitive mechanism controls the release of BTZ in targeted cancer cells, hence developing a novel idea that is applicable in future towards other boronic acid-containing drugs to treat various kinds of health challenges., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Mesoporous silica nanoparticle (MSN) is a novel vehicle to deliver pesticide. MSN can be modified with different chemical groups to increase its interaction with pesticides. In this study, polydopamine-modified mesoporous silica (MSN-PDA) was prepared through a one-pot method with the addition of dopamine (DA). Copper ions, zinc ions, and iron ions were impregnated on MSN-PDA. In addition, avermectin (AVM) was used as the model drug. We investigated the materials' structure, adsorption and release behaviors, anti-UV properties, as well as their adhesive capability, especially the bridge effect of metal ions, π-π stacking of PDA and electrostatic interaction. The results demonstrated that the above materials possessed spherical morphology with surface areas from 635.833 to 1048.960 m 2 /g. Except for the zinc ions, the complexation with copper and iron ions not only enhanced materials' UV resistance but also increased their adsorption rate and the loading amount of AVM from 133 mg/g to 248 and 243 mg/g, respectively. At pH 3, 7, and 10, the bridge effect of the metal ions demonstrated a cumulative release rate using MSN-PDA not over 30% for AVM in 180 h, while the cumulative release rate for MSN reached its 50% in 60, 90, and 50 h under different pH values, respectively. We further demonstrated that the adhesive effect of PDA could be decreased by metal ions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Constructing nanocarriers with high drug loading capacity is a challenge, which limits the effective delivery of drugs to solid tumors. Here, we reported a one-pot synthesis of hollow nanoparticles (NPs) encapsulated by doxorubicin (DOX) and modified with polydopamine (PDA) to form PDA@DOX NPs for breast cancer treatment. PDA@DOX NPs demonstrated exceptionally high capacity (53.16%) for loading DOX. In addition, when PDA@DOX NPs were administered systemically, they exhibited responsive aggregation in the tumor sites and demonstrated a good controlled release effect for DOX due to the weak acidic environment of the tumor sites and targeting near-infrared (NIR) light irradiation. The PDA outer layer absorbed the near-infrared (NIR) light and facilitated simultaneous generation of heat energy for destroying the tumor cells to release the drug upon NIR irradiation. Moreover, this NIR-activated combined/synergistic therapy exhibited remarkably complete tumor growth suppression in a breast cancer mouse model. Importantly, NPs exhibited a good ultrasound performance both in vitro and in vivo, which could monitor the treatment process. In conclusion, this NIR-activated PDA@DOX NP system is demonstrated as a good US-guided combination (chemotherapy + PTT) therapy platform with high loading capacity and controlled drug release characteristics, which is promising for the treatment of breast cancer.

Tumor-associated macrophage (TAM)-related immunotherapy is a greatly promising strategy that involves altering the immunosuppressive tumor microenvironment with the immunomodulator imiquimod (R837) for enhanced cancer therapy. However, the function of R837 is seriously limited due to poor water solubility and a lack of targeting ability. Here, we developed two types of targeting polymer micelles to separately deliver R837 and the anticancer drug doxorubicin (DOX) to TAMs and tumor cells via intratumoral injection and intravenous injection, respectively, for enhanced cancer chemo-immunotherapy against breast cancer. After these micelles accumulated in the tumor tissues, the immunostimulating micelles released R837, which bound to the TLR-7 receptor on the lysosomal membrane within the TAM, stimulating the maturation of the TAM, thereby causing an antitumor immune response and relieving the immunosuppressive effect in the tumor microenvironment. Simultaneously, the chemotherapeutic micelles released DOX in the cytoplasm of the tumor cells, directly inducing cell death. As a result, a synergistic combination of chemotherapy and immunotherapy was achieved through these nanomedicines, which separately activated the antitumor immune response and inhibited tumor cell growth. Therefore, this strategy is a new avenue for the development of targeting nanomedicines for combination chemo-immunotherapy against malignant cancer., (Copyright © 2019 Elsevier B.V. All rights reserved.)