Oligonucleotides‐decorated‐poly(N‐vinyl pyrrolidone) nanogels for gene delivery

Pulsed electron‐beam irradiation of a semi‐dilute poly(N‐vinyl pyrrolidone) (PVP) aqueous solution in the presence of acrylic acid has led to a carboxyl functionalized nanogel system. Nanoparticles hydrodynamic size and surface charge density, in water and as a function of pH, were investigated by dynamic light scattering and laser doppler velocimetry, respectively. Nanogels (NGs) were proved not to be cytotoxic at the cellular level. Indeed, they rapidly bypass the cellular membrane to accumulate in specific cell portions of the cytoplasm, in the perinuclear area. The availability of pendant carboxyl groups on the crosslinked PVP NGs core prompted us to attempt their decoration with a single strand oligonucleotide, which holds a terminal amino group. The recognition ability of the attached single helix of its complementary strand was investigated. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39774.     

Design and study of the potential of crosslinked cationic polymers as drug delivery systems for dermal application

Crosslinked carriers based on cationic monomer [2‐(acryloyloxy)ethyl]trimethylammonium chloride or 2‐(dimethylamino)ethyl methacrylate were developed and investigated as new platform for ibuprofen transdermal delivery. Series of networks of varied composition and structure were synthesized and characterized by FTIR spectroscopy and following swelling kinetics in different solvents. Dermal safety tests to examine the skin irritation and sensitization potential of the network films were performed in vivo. Chosen network compositions were loaded with ibuprofen by swelling in its ethanol solution. The structures of the drug carriers were investigated by scanning electron microscopy. Ibuprofen release from the developed drug delivery systems was followed in phosphate buffer solution at 37 °C. The investigation proved the feasibility of the developed cationic copolymer networks as effective platforms with modified ibuprofen release for potential dermal application. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46420.     

Fabrication of a tunable hydrogel membrane for constructing indirect cell coculture system

In this study, an improved indirect cell coculture system was constructed by using a polyelectrolyte complex membrane generated by alginate (A) and chitosan (C). Methodologies of characterizing thickness and permeability of flat AC membrane were first established due to the importance of these two parameters in determining intercellular distance and degree of contact between cocultured cells. Compared to reaction time, both alginate concentration and molecular weight (M_w) of chitosan play more dominant roles in determining the membrane thickness and diffusion coefficients. Moreover, cells in the alginate gel and on the AC membrane could maintain high cell viability. Thus, an improved indirect cell coculture system constructed by flat AC membrane was fabricated and characterized, which provides a robust tool to study the effect of intercellular distance and degree of contact between cocultured cells on cell–cell interactions. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43100.     

Microporous PDMAEMA‐based stimuli‐responsive hydrogel and its application in drug release

The microporous hydrogels (Pn‐Cm gels) composed of poly(dimethylaminoethyl methacrylate) and carboxymethylchitosan were synthesized in situ radical polymerization by using nano γ‐Fe₂O₃ particles as pore‐agent. The microporous structure formed through eliminating the Fe₂O₃ particles was designed to achieve a faster response rate and better drug loading effect. Comparing to the neat gels, Pn‐Cm gels exhibit deteriorative mechanical properties with the increased pores, while the gels still keep the elastic network structure which could bear some degree of tensile and compression deformation. Meantime, Pn‐Cm gels show similar temperature and pH double responsiveness with same isoelectric point shrink as that of neat gels, the swelling ability decreases slightly, and the deswelling rate increases with the increase of pores. Moreover, the 5‐fluorouracil was used as a target drug to explore the potential of this gel applied as drug‐release system. For Pn‐Cm gels, the more pores and carboxymethyl chitosan inside the gels are beneficial to the drug loading, all gels show a burst release of drug, being followed by a slow and sustained release with different rate. Comprehensively, the Pn‐Cm gels exhibit a better sustained release effect in the simulated stomach condition (pH = 2.1), the related release mechanism could be interpreted by the superposition of Fickian diffusion. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45326.     

Retentive drug delivery systems based on shape memory materials

Retentive drug delivery systems are intended for prolonged residence and release inside hollow organs of the body, in pursuit of either local or systemic therapeutic goals. Because of the relatively long-lasting period of time they could cover during operation, a primary advantage arising from their use would lie in reduced dosing frequency, thereby improving the overall adherence of patients to prescribed medication regimens. The treatment of numerous pathologies that affect the urinary bladder and the stomach could especially benefit from viability of such delivery technologies. Moreover, by making use of effective gastroretentive dosage forms, the bioavailability of drugs that are preferably absorbed from the upper gastrointestinal tract could be increased. Expansion of devices following administration is often exploited for retention purposes, and several formulation strategies have been proposed in this respect. Innovative applications of shape memory materials have also been explored, highlighting the great inherent potential for facing the challenges involved. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48798.     

Structure–property correlation of silicone hydrogels based on 3-[tris(trimethylsilyloxy)silyl]propyl methacrylate monomer

We have investigated silicone-based hydrogels highlighting the effect of silyl comonomer, method of polymerization and nature of cross-linker on their bulk as well as surface properties. Transmission electron microscopy results showed that solution thermal polymerization mitigated phase segregation of hydrophobic siloxane components over bulk thermal polymerization. 2-hydroxyethyl methacrylate cannot provide transparent hydrogels with 3-[tris(trimethylsilyloxy)silyl]propyl methacrylate alone and requires equal weight percent of N, N-dimethylacrylamide to compatibilize the comonomers to yield a silicone hydrogel network showing no microphase separation. The differentiated surface properties of silicone hydrogels containing varying amount of siloxane comonomers were also unraveled and rationally supported by surface infrared spectroscopic results. Different molecular states of water entrapped within hydrogel network were identified to understand the nature of gel-mesh functionality. The effect of silicone pendant groups on the gel elasticity was also explored.     

Developing antibacterial surgical adhesives: An enhancement of cyanoacrylate polymers

Surgical site infections (SSIs) and traumatic wounds have a significant risk of becoming contaminated by microbial pathogens of both endogenous and nosocomial origins, including Staphylococcus aureus and Enterococci sp.. One preventative approach is to protect wounds from infection by using a rapidly curing adhesive to seal the wound and prevent further contamination. Here, we demonstrate the covalent incorporation of an antimicrobial, quaternary ammonium chloride monomer (quat) into a 2-octyl cyanoacrylate (2oc) polymer adhesive. Copolymerization was confirmed via nuclear magnetic resonance spectroscopy. Cytotoxicity of the copolymer was assessed against: S. epidermidis and E. coli, and 3T3 mouse fibroblasts. The CA-Quat polymer was found to exhibit dose-dependent bacteriostatic and bactericidal effects against both E. coli and S. epidermidis, importantly without showing any demonstrable toxicity against mammalian 3T3 fibroblast cells. The described experiments provide promising data to suggest successful copolymerization, effective antibacterial properties, and remarkably low cytotoxic effects of the copolymer on mammalian cells.     

Microemulsion of erythromycine for transdermal drug delivery

The aim of this work was to prepare an erythromycin (EM) microemulsion (EM‐ microemulsion) for transdermal EM delivery using isotropic mixtures of oil and aqueous phases. The prepared EM‐microemulsion is a white dispersion, with a suitable viscosity for transdermal delivery. In stability experiments, the EM‐microemulsion showed no marked change in appearance for up to 3 weeks at 25°C. In accelerated stability experiments at 37 and 60°C, however, precipitated crystalline EM particles were observed in the EM‐microemulsion. Diffusion of EM into the skin exhibited a first order release profile. Fluorescein (FL)‐microemulsion penetrated to the dermis layer of skin. In conclusion, we confirmed that EM‐microemulsion could serve as an excellent transdermal carrier of EM. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Chitosan hydrogel covalently crosslinked by gold nanoparticle: Eliminating the use of toxic crosslinkers

Tissue engineering has directed a lot of effort toward the development of devices with suitable biocompatibility and mechanical properties. Chitosan has been pointed as a valuable material to be applied in scaffolds due to its antimicrobial activity and biocompatibility. Nevertheless, the low mechanical resistance associated with the requirement of toxic crosslinkers has hampered translational application of chitosan hydrogel. Herein, the use of gold nanoparticles (AuNP) as crosslinker is reported as a great strategy to obtain chitosan hydrogel without using toxic reactants. In addition, the resultant chitosan hydrogel, crosslinked by AuNP of 30 nm (AuNP30), presented outstanding properties compared to chitosan hydrogel crosslinked by glutaraldehyde. Chitosan hydrogel crosslinked by AuNP30 presented lower porosity, which provided lower swelling degree and slower degradation rate. In addition, compressive strength was about two times higher than the chitosan hydrogel crosslinked by glutaraldehyde. The crosslink by AuNP30 also increased the biocompatibility of the hydrogel. Chitosan hydrogel crosslinked by AuNP30 did not show cytotoxicity against MEF cells, whereas cell viability of cells incubated with extract from chitosan hydrogel crosslinked by glutaraldehyde was only 41%. In conclusion, the results reported herein pointed that the use of AuNP30 as crosslinker agent provided to chitosan hydrogel enhanced properties that made it suitable to application in biomedical devices.     

Design and characterization of pH stimuli-responsive nanofiber drug delivery system: The promising targeted carriers for tumor therapy

New carrier platforms have been designed for an electrospun pyridinium calixarene nanofiber for controlled drug delivery. First, 5,11,17,23-tetra-tert-butyl-25,27-bis(3-aminomethyl-pyridineamido)-26,28-dihydroxycalix[4]arene (3-AMP) scaffold was produced by electrospinning. AMP scaffold was modified by human serum albumin (HSA), folic acid (FA), and glutathione (GSH). Doxorubicin (DOX) was loaded to surfaces of the AMP, AMP-HSA, AMP-HSA-FA, and AMP-HSA-GSH nanofibers by using DOX solution in different buffers with, 2.2, 4.0, 6.0, and 7.4 pH. The release studies DOX from four different nanofibers was also done in a various amount microenviroments by changing pH values. The loading and release amount of DOX was estimated from the calibration curve drawn at 480 and 560 nm of excitation and emission wavelengths by using a fluorescence spectrophotometer. The loading studies were confirmed by Fourier transforms infrared, atomic force microscopy, transmission electron microscopy, scanning electron microscope, and energy-dispersive X-ray (EDX) analysis.     

Preparation and optimization of calcium pectate beads for cell encapsulation

A variety of natural polymers are considered suitable for cell entrapment. Pectin, a natural polysaccharide found in the cell walls of all higher terrestrial plants, presents great potential for cell encapsulation because of its ability to form gels. In this study, we investigated the influences of intrinsic and extrinsic factors on the formation and properties of calcium pectate (CP). Beads of CP prepared with 30–35% methyl esterification presented improved gel properties. The molecular weight (M_w), calcium content, and gel time did not significantly affect the gel properties. The gelling properties, sphericity factor (SF), and swelling ratio were significantly influenced by the degree of methyl esterification (DE) and pectin concentration. The DE (<40%), M_w, and calcium concentration had negative effects on the SFs of CP beads. Moreover, increases in the DE (<40%) and pectin concentration increased the swelling ratio. The C3A cells encapsulated in optimized CP beads maintained good viability and proliferation for up to 2 weeks. In conclusion, CP beads are a potential encapsulation material for cell immobilization and application in related fields. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45685.     

Zein nanoparticle‐embedded electrospun PVA nanofibers as wound dressing for topical delivery of anti‐inflammatory diclofenac

Bioactive wound dressings from poly(vinyl alcohol) (PVA) and zein nanoparticles (NPs) loaded with diclofenac (DLF) were prepared successfully by the single jet electrospinning method. DLF‐loaded zein NPs with an average diameter of ～228 nm were prepared using anti‐solvent precipitation method. The formulation of zein:DLF 1:1 exhibited optimum encapsulation efficiency of 47.80%. The NPs were characterized by dynamic light scattering, zeta‐potential measurement, and differential scanning calorimetry. In vitro, drug release profiles of the DLF‐loaded zein NPs, and PVA–zein NPs were also studied within 120 h and showed the release efficiency of nearly 80% from zein NPs. A more controlled release of DLF was achieved by embedding the zein NPs in the PVA nanofibers. Fourier transform infrared spectroscopy was used to analyze possible interactions between different components of the fabricated dressings. The mechanical properties of the developed dressings were also evaluated using uniaxial tensile testing. Young's modulus (E) of the dressings decreased after inclusion of zein NPs within the PVA nanofibers. Moreover, fibroblast culturing experiments proved that the composite dressings supported better cell attachment and proliferation compared to PVA nanofibers, by exhibiting moderate hydrophilicity. The results suggested that the electrospun composite dressing of PVA nanofibers and zein NPs is a promising topical drug‐delivery system and have a great potential for wound healing application. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46643.     

Glass microparticle- versus microsphere-filled experimental dental adhesives

This study aimed to formulate antibacterial dental adhesives. Phosphate-substituted methacrylate adhesives were modified with 0–20 wt % copper-doped glass microparticles. Two shapes of microparticles were used: regular shaped (microspheres) and irregular shaped (microparticles). The morphology/composition, roughness, monomer conversion (DC%), thermogravimetric analysis, and antibacterial action against S. mutans and P. aeruginosa and ion release were investigated. The results showed that microspheres produced adhesives with a relatively smoother surface than microparticles did. The DC% of adhesives increased with increasing glass filler content. Filled adhesives showed polymer decomposition at ~315 °C and glass melting at 600–1000 °C. The weight loss percent of adhesives decreased with increasing weight percent of fillers. Glass microparticles at 0–20 wt % significantly increased the antibacterial action of adhesives against both bacteria. Glass microspheres at 0–5 wt % significantly increased the antibacterial action of adhesives against both bacteria. Only 20 wt % microparticle-filled adhesive showed an inhibition zone similar to tobramycin (positive control). Microparticle-filled adhesives (with >5 wt % filler) significantly reduced S. mutans more than their microsphere counterparts. Microsphere-filled adhesives (with ≤5 wt % filler) significantly reduced P. aeruginosa more than their microparticle counterparts. Microsphere-filled adhesives showed higher Cu release than their microparticle counterparts. Accordingly, phosphate-substituted methacrylate filled with glass could be used as an antibacterial adhesive. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47832.     

Temperature stimuli-responsive nanoparticles from chitosan-graft-poly(N-vinylcaprolactam) as a drug delivery system

This work describes the preparation of thermosensitive chitosan-graft-poly(N-vinylcaprolactam) nanoparticles by ionic gelation and their potential use as a controlled drug delivery system, using doxorubicin as a model drug. A systematic study of the effect of the main processing parameters on both the size and thermoresponsive behavior of nanoparticles was investigated. The size of the particles is strongly dependent on the length of the poly(N-vinylcaprolactam) grafted chains and the concentration of the copolymer and crosslinking agent solutions. The molecular structure of the copolymer plays an essential role in the phase transition temperature of the particles, which decreases with the length of PVCL grafted chain. The system displayed proper drug-association parameters, and the drug-loaded nanoparticles exhibited dose-dependent cytotoxicity. A significant increase in the doxorubicin delivery rate was observed above the phase transition temperature (40 °C). These features indicate that these nanoparticles are suitable for the development of a new thermally controlled anti-cancer drug delivery system. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47831.     

Design of intelligent chitosan/heparin hollow microcapsules for drug delivery

In this study, a novel strategy has been developed for the assembly of polyelectrolyte multilayer (PEM) on CaCO₃ templates in acidic pH solutions, where consecutive polyelectrolyte layers (heparin/poly(allylamine hydrochloride) or heparin/chitosan) were deposited on PEM hollow microcapsules established previously on CaCO₃ templates. The PEM build‐up, hollow capsule characterization and successful encapsulation of fluorescein 5(6)‐isothiocyanate (FITC)‐Dextran by coprecipitation with CaCO₃ are demonstrated. Improvement by the removal of CaCO₃ core was achieved while the depositions. In the course of the release profile, high retardation for encapsulated FITC‐Dextran was observed. The combined shell capsules system is a significant trait that has potential use in tailoring functional layer‐by‐layer capsules as intelligent drug delivery vehicles where the preliminary in vitro tests showed the responsiveness on the enzymes. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44425.     

Electrostatic immobilization of cetylpyridinium chloride to poly(vinyl alcohol) hydrogels for the simple fabrication of wound dressings with the suppressed release of antibacterial agents

Polymeric systems for antibacterial wound dressings require chemical reactions or syntheses for attaching or incorporating antibacterial moieties into polymer backbones. However, these materials often fail to satisfy the basic requirements, such as easy and inexpensive synthesis. We speculated that a positively charged organic antibacterial agent would be attracted to the polar groups of poly(vinyl alcohol) (PVA) hydrogels and would show suppressed release. PVA hydrogels containing cetylpyridinium chloride (CPC) were prepared by γ irradiation. CPC was barely released from the hydrogels, probably because of electrostatic interactions, and was stable upon γ irradiation. The suppressed release of CPC conferred antibacterial activity against Escherichia coli to the surface of the hydrogels, whereas no inhibition zone was observed around the hydrogels. The CPC‐containing PVA hydrogels were easy to prepare and contained known and safe materials. The simplicity and safety of this procedure for achieving the suppressed release of antibacterial agents were advantages of these CPC‐containing PVA hydrogels. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40456.     

Photoactive mussels inspired polymer coatings: Preparation and antibacterial activity

In this article we report on the facile preparation of photoactive antibacterial mussel inspired polymer coatings deposited on a stainless steel (SS) substrate from water based precursors. The coating is prepared by the sequential deposition of aqueous based solutions of an anchoring layer based on bio-inspired glue, a cationic polymer bearing pendent catechols, a nanogel decorated by ortho-quinones and a photosensitizer of the aminoacridine type. This latter is grafted to the coating by reaction of its amino group with the o-quinone of the deposited nanogel. The deposition of all layers is followed in-line by Quartz crystal microbalance coupled with dissipation (QCM-D) and AFM shows that the thin polymer film repeated the roughness of the SS substrate. The prepared coatings show good mechanical properties applying nanoindentation techniques. The established antibacterial activity of the prepared photoactive polymer coatings on SS against Gram-negative E. coli strain demonstrate their potential as a power tool for medical applications.     

Development of a poloxamer analogs/bioadhesive polymers‐based in situ gelling ophthalmic delivery system for tiopronin

The purpose of this study was to develop a poloxamer analogs/bioadhesive polymers‐based in situ gelling ophthalmic delivery system aiming at enhancing bioavailability and anticataract effect. The effect of poloxamer 407 (P407), poloxamer 188 (P188), carbopol 934P (C934), and sodium hyaluronate (NaHA) concentration on the gelation temperature (GT) was examined. The GT of P407 based in situ gel increased with an increase in the P188 concentration. NaHA and C934 lowered the GT of poloxamer analogs based in situ gel. Correlation analysis demonstrated that in vitro drug release from in situ gel was controlled by gel dissolution and followed zero‐order kinetics. Tiopronin in vitro transcorneal transit accorded with zero‐order kinetics. Twenty‐two percent P407 and 6% P188 containing 0.2% NaHA based formulation can be chosen as in situ gel matrix of tiopronin because of proper GT and sustained releasing ability. In vivo study showed that the area under the aqueous humor–concentration time curve of tiopronin increased by 1.6 folds for in situ gel, compared with tiopronin aqueous solution. High‐dose tiopronin in situ gel and solution delayed the development of selenite cataract 6 d and 4 d, respectively. The results showed that tiopronin in situ gel exhibits higher bioavailability and therapeutical effect. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

5‐Fluorouracil encapsulated magnetic nanohydrogels for drug‐delivery applications

For the first time, green‐tea (GT)‐based magnetic nanohydrogels were developed for drug‐delivery purposes. The hydrogel matrices were fabricated via the in situ polymerization of acrylamide with GT molecules. Magnetic nanoparticles were synthesized by the reduction of the 1:2 molar ratio mixture of ferrous sulfate heptahydrate and ferric chloride hexahydrate with an ammonia solution. A chemotherapeutic drug, 5‐fluorouracil, was chosen as a model drug, and its releasing profiles in the presence and absence of the external magnetic field were evaluated at a pH of 7.4. We observed that in the presence of the applied magnetic field, these magnetic nanohydrogels released 2.86% more drug than in the absence of a magnetic field. The magnetic nanohydrogels were characterized by X‐ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, vibrating sample magnetometry, and transmission electron microscopy. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43921.