Synthesis of polyhedral oligomeric silsesquioxane nano‐crosslinked poly(ethylene glycol)‐based hybrid hydrogels for drug delivery and antibacterial activity

The synthesis is reported of novel hybrid hydrogels based on ethylenediaminetetraacetic acid dianhydride and poly(ethylene glycol) (PEG) with octa‐aminopropyl polyhedral oligomeric silsesquioxane hydrochloride salt (OA‐POSS) as a nano‐crosslinker under solvent‐free conditions. The molecular weight of PEG was varied between 600 and 1000 Da. The synthesized hydrogels were characterized using various techniques. Further, the swelling behavior and antibacterial activity of the hydrogels and release kinetics of metronidazole (MTZ) as a model drug from them were evaluated. Experimental results demonstrate that hydrogels with tunable properties can be synthesized by varying the PEG molecular weight and type of crosslinker (hybrid or organic). Among the synthesized hybrid hydrogels, that crosslinked by OA‐POSS with long PEG chains (1000 Da) showed the highest swelling degree (2000%), drug encapsulation efficiency (88%) and extent of MTZ release (96%). © 2018 Society of Chemical Industry     

Polypropylene oxide/polyethylene oxide-cellulose hybrid nanocomposite hydrogels as drug delivery vehicle

This article deals with the synthesis of hybrid nanocomposite hydrogels through the combination of cellulose (C), polypropylene oxide/poly ethylene oxide (PPO/PEO), and silver nanoparticles (AgNPs) by in situ polymerization technique for the in vitro release of ornidazole drugs. The structure of the resulted materials is identified using SEM, XRD, FTIR, XPS, and TGA spectroscopic techniques. The resulting structure, morphology, thermo responsive property, water retention, and swelling behavior of hydrogels are investigated. The rheological measurement is studied to establish the enhancement of the viscoelasticity and stiffness of hydrogels. The antibacterial activity of the biodegradable silver hybrid nanocomposite hydrogel is investigated by inhibition zone method against gram positive and negative bacteria. Maximum drug release of 96.4% is recorded at 7.4 pH in 5 h. The biocompatibility and cytotoxicity of the hybrid nanocomposite hydrogel are verified using mouse fibroblast cell line L-929 (ATCC CCL-1) cells for their possible use as controlled drug delivery vehicles. The nontoxic nature makes the materials more biocompatible and suitable to apply in the biological systems. Therefore, nontoxic and biocompatible natures of present materials with improved thermal and rheological properties support for their possible uses as drug delivery vehicles.     

Chitosan‐modified nanoclay–poly(AMPS) nanocomposite hydrogels with improved gel strength

BACKGROUND: Making (nano)composite structures is one of the efficient approaches for strengthening hydrogels extended in recent years. The present paper deals with the synthesis and properties of novel nanocomposite hydrogels based on 2‐acrylamido‐2‐methylpropane‐1‐sulfonic acid (AMPS). Initially, a bio‐modified clay, chitosan‐intercalated montmorillonite (chitoMMT), was prepared. Then, this was incorporated into the polymerization of AMPS in the presence of a macro‐crosslinker, i.e. poly(ethylene glycol) dimethacrylate, to yield super‐swelling nanocomposite hydrogels. The swelling capacity as well as some structural, rheological and thermomechanical properties of the hydrogels were studied and compared with those of the clay‐free counterpart. RESULTS: ChitoMMT exhibited no toxicity, which was confirmed using cell‐culture testing. A chitoMMT content of ca 6% was found to be the most favourable content of the bio‐modified clay for achieving a product with improved properties (i.e. the highest gel content, the highest gel strength and optimal thermal stability). Based on a dynamic mechanical thermal analysis study, an increased glass transition temperature (98.2 °C) and improved rubbery modulus (up to 238% higher than that of the clay‐free counterpart) were recorded. Thermogravimetric analysis verified that the thermal stability of nanocomposite samples was higher than that of clay‐free samples. CONCLUSION: Owing to the non‐toxicity of the incorporated chitoMMT, the strengthened hydrogels may be considered as potential candidates for bio‐applications. Copyright © 2009 Society of Chemical Industry     

Exploring poly(vinyl alcohol) hydrogels containing drug–cyclodextrin complexes as controlled drug delivery systems

Poly(vinyl alcohol) (PVA) hydrogels containing drug–β‐cyclodextrin inclusion complexes (ICs) were synthesized with glutaraldehyde (GA) as a crosslinker. The role of cyclodextrin (CD), the effect of the nature of drug, and the degree of crosslinking on the drug‐release process were investigated. The probable mechanism of drug release was also explored. Controlled release of the drug was achieved from the hydrogels containing the ICs. The nature of the drug, in terms of its binding efficacy with CD, played an important role. The effect of the degree of crosslinking on the release pattern was strikingly different from that in the hydrogels containing free drug and those with ICs. The role of CD in the drug‐release process was not only due to its inclusion ability but also its effect on the polymer relaxation. GA, apart from crosslinking PVA, probably interacted with the cyclodextrins and, thereby, influenced the matrix structure and the drug‐release kinetics. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40318.     

Preparation of poly(ethylene glycol)/chitosan membranes by a glucose‐mediating process and in vitro drug release

Novel pH‐dependent chitosan/poly(ethylene glycol) (PEG) membranes were developed for oral drug delivery. The preparation of these membranes involved a solution‐mediating process with glucose addition at different pHs. Fourier transform infrared/attenuated total reflectance showed that the Schiff‐base reaction was favored at high pHs and high glucose concentrations. X‐ray diffraction analysis showed a continuous increase in the glucose addition transformed the chitosan/PEG samples into amorphous polymers. The equilibrium swelling measurements showed that the swelling ratio of the solution‐mediated membranes decreased as the glucose concentration increased, and this was demonstrated by degree‐of‐mediation analysis. The glucose‐mediated membranes had different degrees of mediation, which depended on the pH and glucose concentration. The in vitro release profiles of theophylline‐loaded, pH 6 treated, glucose‐mediated membranes showed that the theophylline release decreased as the glucose concentration increased. Also, the release behavior of the theophylline from the glucose‐mediated membranes varied with the pH of the release medium, the glucose concentration, and the final pH of the glucose‐mediated chitosan/PEG gels. Chitosan/PEG membranes prepared by a basic glucose‐mediated process could lead to successful applications in localized drug delivery to the intestine. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1083–1094, 2005     

Phthalyl chitosan–poly(ethylene oxide) semi‐interpenetrating polymer network microparticles for oral protein delivery: An in vitro characterization

Polyhydroxybutyrate (PHB) is generally considered to be a very uneasy biopolymer to handle because of significant instability during melt processing and some excessive brittleness. This work studied the morphological, thermal, and barrier properties of novel melt-mixed nanobiocomposites of PHB, poly(ε-caprolactones) (PCL), and layered phyllosilicates based on commercial organomodified kaolinite and montmorillonite clay additives. The addition of PCL component to the blend was seen to reduce oxygen permeability but it was also found to lead to a finer dispersion of the clay. The addition of highly intergallery swollen organomodified montmorillonite clays to the PHB blend led to a highly dispersed morphology of the filler, but this simultaneously increased to a significant extend the melt instability of the biopolymer. Nevertheless, the organomodified kaolinite clay, despite the fact that it was found to both lead to less dispersed and irregular morphology, particularly for higher clay loadings, it led to enhanced barrier properties to oxygen, D -limonene, and water. D -limonene and specially water molecules were, however, found to sorb in both hydrophobic and hydrophilic sites of the filler, respectively, hence diminishing the positive barrier effect of an enlarged tortuosity factor in the permeability. Mass transport properties were found to depend on the type of penetrant and modeling of the permeability data to most commonly applied formalisms was not found to be satisfactory because of factors such as morphological alterations, heterogeneity in the clay dispersion, and penetrant solubility in the filler. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Iodine-loaded poly(silicic acid) gellan nanocomposite mucoadhesive film for antibacterial application

Iodine-loaded poly(silicic acid) gellan nanocomposite film was fabricated and evaluated for antibacterial properties. Poly(silicic acid) nanoparticles were synthesized by condensation of silicic acid under alkaline conditions in the presence of polyvinyl pyrrolidone, phosphate ions, and molecular iodine. The nanoparticles were incorporated into gellan dispersion to prepare gellan nanocomposite film using the solvent casting method. The nanocomposite films were characterized by Fourier transformed infrared spectroscopy, thermogravimetric analysis, and X-ray diffraction studies. The results of characterization studies indicated improved thermal stability and an increase in the degree of crystallinity. The scanning electron micrographs and energy dispersive X-ray spectrum confirmed the uniform dispersion of silica and iodine in the nanocomposite films. The analysis of physical and mechanical properties revealed the enhanced tensile strength, moisture resistance, and higher folding endurance of poly(silicic acid) gellan nanocomposite films as compared to gellan film. Further, the iodine-loaded poly(silicic acid) gellan nanocomposite films showed good antibacterial activity against Staphylococcus aureus and Escherichia coli and effective mucoadhesive strength. The results indicate that iodine-loaded poly(silicic acid) gellan nanocomposite mucoadhesive film can be used for potential antibacterial applications in pharmaceuticals.     

Self‐assembled micelles prepared from poly(ɛ‐caprolactone)–poly(ethylene glycol) and poly(ɛ‐caprolactone/glycolide)–poly(ethylene glycol) block copolymers for sustained drug delivery

A series of poly(?‐caprolactone)–poly(ethylene glycol) (PCL‐PEG) and poly(?‐caprolactone/glycolide)–poly(ethylene glycol) [P(CL/GA)‐PEG] diblock copolymers were prepared by ring‐opening polymerization of ?‐caprolactone or a mixture of ?‐caprolactone and glycolide using monomethoxy PEG (mPEG) as macroinitiator and Sn(Oct)₂ as catalyst. The resulting copolymers were characterized using ¹H‐NMR, gel permeation chromatography, differential scanning calorimetry, and wide‐angle X‐ray diffraction. Copolymer micelles were prepared using the nanoprecipitation method. The morphology of the micelles was spherical or worm‐like as revealed by transmission electron microscopy, depending on the copolymer composition and the length of the hydrophobic block. Introduction of the glycolide component, even in small amounts (CL/GA = 10), disrupted the chain structure and led to the formation of spherical micelles. Interestingly, the micelle size decreased with the encapsulation of paclitaxel. Micelles prepared from mPEG5000‐derived copolymers exhibited better drug loading properties and slower drug release than those from mPEG2000‐derived copolymers. Drug release was faster for copolymers with shorter PCL blocks than for those with longer PCL chains. The introduction of glycolide moieties enhanced drug release, but the overall release rate did not exceed 10% in 30 days. In contrast, drug release was enhanced in acidic media. Therefore, these bioresorbable micelles and especially P(CL/GA)‐PEG micelles with excellent stability, high drug loading content, and prolonged drug release could be promising for applications as drug carriers. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45732.     

Chitosan/poly(lactic acid) blends as drug delivery systems

Abstract

The immobilization and controlled release of salicylic acid (SA) in chitosan/poly(lactic acid) (Ch/LA) blends were studied in the present work. The Ch/PLA bland’s morphology was studied by SEM. FT-IR and DSC were used to investigate the interactions between the polymer matrix and the SA. The SA release kinetics was interpreted by the Weibull and Higuchi models. The SA release was the fastest in Ch/PLA systems with inhomogeneous and porous structure. It was slower in neat PLA matrix due to its dense structure and hydrophobic behavior, and in neat chitosan matrix, because of specific electrostatic chitosan/SA interactions and complex formation.     

Design of a drug delivery system based on poly(acrylamide‐co‐acrylic acid)/chitosan nanostructured hydrogels

To obtain biodegradable materials for biomedical applications, new biopolymeric hydrogels based on blends of polyacrylamide nanoparticles and chitosan have been prepared. In this work, we have studied the behavior of the diffusion of ascorbic acid (V‐C) from poly(acrylamide‐co‐acrylic acid)/chitosan nanostructured hydrogels. The process involves the synthesis of nanoparticles of polyacrylamide by inverse microemulsion polymerization and their complexation with chitosan dissolved in an acrylic acid aqueous solution. We have studied the effect of the concentration of the polyacrylamide nanoparticles, which are crosslinked with N,N′‐methylenebisacrylamide, in the delivery of V‐C. The results indicate that the drug delivery operates by a non‐Fickian mechanism. Also, we have obtained the diffusion coefficient for V‐C in gels for different nanoparticle concentrations, using a modified form of Fick's second law that takes into account dimensional changes in the hydrogels during drug release. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Nanostructured membranes based on sulfonated poly(aryl ether sulfone) and silica for fuel‐cell applications

Nanostructured sulfonated poly(aryl ether sulfone) (SPSU) membranes were made from SPSU/silica composites through the addition of amorphous, precipitated, and micronized silica particles (Tixosil 333) and short or segmented linear structures. Linear and branched segments of silica were obtained from the in situ reaction of tetraethoxysilane (TEOS) in an SPSU solution through a sol–gel acid‐catalyzed process. Different amounts of silica in the SPSU composites were prepared to evaluate their influence on the ionic conductivity, the water and alcohol solution sorption capacities, and the stability in an ethanol medium. The effect of silica (Tixosil) on the conductivity was higher than that of the silica made from TEOS in SPSU composites. The conductivities of the membranes containing 10% Tixosil and 6.6% silica prepared from TEOS were measured at 80°C; their values were 60 and 33 mS/cm, respectively. Furthermore, a membrane made of a silica blend (5% Tixosil and 3% TEOS) in SPSU attained a value of 92 mS/cm, whereas the commercial membrane Nafion 117, used as a reference, had a conductivity of 54 mS/cm measured under the same conditions. All those composites membranes could be used as components in hydrogen fuel cell. However, only the SPSU/2% Tixosil composite could be used in both hydrogen and ethanol direct fuel cells. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Synthesis and characterization of hybrid membranes using poly(vinyl alcohol) and tetraethylorthosilicate for the pervaporation separation of water–isopropanol mixtures

Hybrid membranes were prepared using poly(vinyl alcohol) (PVA) and tetraethylorthosilicate (TEOS) via hydrolysis and cocondensation reaction for the pervaporation separation of water‐isopropanol mixtures. The resulting membranes were characterized by Fourier transform infrared spectroscopy, wide‐angle X‐ray diffraction, and differential scanning calorimetry. The glass transition temperature of these membranes varied from 100 to 120°C with increasing TEOS content. Effects of crosslinking density and feed compositions on the pervaporation performances of the membranes were studied. The membrane containing 1.5:1 mass ratio of TEOS to PVA gave the highest separation selectivity of 900 at 30°C for 10 mass % of water in the feed mixture. It was found that the separation selectivity and permeation flux data are strongly dependent on the water composition of the feed and operating temperature. However, the membrane with the highest crosslinking density showed unusual pervaporation properties. The overall activation energy values were calculated using the Arrhenius‐type equation. The activation energy values for the permeation and diffusion varied from 49.18 to 64.96 and 55.13 to 67.31 kJ/mol, respectively. Pervaporation data have also been explained on the basis of thermodynamic quantities. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1304–1315, 2004     

Calcium‐carboxymethyl chitosan hydrogel beads for protein drug delivery system

In this study, carboxymethyl chitosan (CMC) hydrogel beads were prepared by crosslinking with Ca²⁺. The pH‐sensitive characteristics of the beads were investigated by simulating gastrointestinal pH conditions. As a potential protein drug delivery system, the beads were loaded with a model protein (bovine serum albumin, BSA). To improve the entrapment efficiency of BSA, the beads were further coated with a chitosan/CMC polyelectrolyte complex (PEC) membrane by extruding a CMC/BSA solution into a CaCl₂/chitosan gelation medium. Finally, the release studies of BSA‐loaded beads were conducted. We found that, the maximum swelling ratios of the beads at pH 7.4 (17–21) were much higher than those at pH 1.2 (2–2.5). Higher entrapment efficiency (73.2%) was achieved in the chitosan‐coated calcium‐CMC beads, compared with that (44.4%) in the bare calcium‐CMC beads. The PEC membrane limited the BSA release, while the final disintegration of beads at pH 7.4 still leaded to a full BSA release. Therefore, the chitosan‐coated calcium‐CMC hydrogel beads with higher entrapment efficiency and proper protein release properties were a promising protein drug carrier for the site‐specific release in the intestine. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 3164–3168, 2007     

New carbon nanotube–conducting polymer composite electrodes for drug delivery applications

A novel drug delivery system (DDS) based on a carbon nanotube (CNT)–poly(3,4‐ethylenedioxythiophene) (PEDOT) composite was constructed via a layering method. Single‐walled CNTs (SWNTs) were immobilized on a gold electrode using a layer‐by‐layer technique. In particular, cysteamine (Cys) was firstly bonded to the gold surface through the strong S? Au association and SWNTs were subsequently linked onto the Cys layer through condensation reaction of ? NH₂ and carboxyl groups by 1‐ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide/N‐hydroxysuccinimide coupling. X‐ray photoelectron spectroscopy and Raman spectroscopy demonstrate that this is a facile route for immobilizing CNTs on gold electrodes. Finally PEDOT was electropolymerized on the SWNT‐functionalized electrode to make a SWNT–PEDOT composite, and the modified electrode was applied as a DDS. Dexamethasone, as a model drug, was incorporated into PEDOT in the electropolymerization. Investigations of the electrochemical properties of SWNT–PEDOT demonstrate that SWNTs greatly improve the conductivity and increase the charge capacity of PEDOT. The composite exhibits a petal‐like surface structure, 20–30 nm thick and 100–200 nm wide. Compared to a DDS based on pure PEDOT synthesized under the same conditions, SWNT–PEDOT has the merits of higher drug release rate and larger release amount. The average mass release for every five voltammetry cycles increases from 1.4126 to 1.8864 mg cm^?2. Copyright © 2011 Society of Chemical Industry     

Preparation and characterization of acrylic resin/titania hybrid nanocomposite coatings by photopolymerization and sol–gel process

Titania‐containing coatings were prepared through a dual‐cure process involving radical photopolymerization of a polysiloxane diacrylate and subsequent condensation of alkyltitanate groups. The kinetics of photopolymerization and condensation reaction was investigated as a function of the inorganic phase precursor (titanium tetraisopropoxide) content. AFM analysis gave evidence of a strong interaction between the organic and inorganic phase with the formation of titania domains in the nanoscale region. An increase of hydrophilicity in the coatings surface with increasing TiO₂ content was evidenced. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 4659–4664, 2006     

Properties of chitosan/poly(vinyl alcohol) films for drug‐controlled release

With bovine serum albumin (BSA) as a model drug, drug‐loaded films of chitosan (CS) and poly(vinyl alcohol) (PVA) were obtained by a casting/solvent evaporation method and crosslinked by tripolyphosphate (TPP). The films were characterized by FTIR, XRD, and SEM. The influential factors of drug‐loaded films on drug‐controlled release were studied. These factors included, primarily, the component ratio of CS and PVA, the loaded amount of BSA, the pH and ionic strength of the release solution, and the crosslinking time with TPP. The results showed that within 25 h, when the weight ratios of CS to PVA in the drug‐loaded films were 90 : 10, 70 : 30, 50 : 50, and 30 : 50, the cumulative release rates of BSA were 63.3, 72.9, 81.8, and 91.8%, respectively; when the amounts of model drug were 0.1, 0.2, and 0.3 g, the release rates were 100, 81.8, and 59.6%, respectively; when the pH values of the drug release medium were 1.0, 3.8, 5.4, and 7.4, the release rates reached 100, 100, 37.9, and 7.8%, respectively; the cumulative release rates of BSA were 78.4, 82.3, 84.3, and 91.7% when the ionic strengths of the release solution were, respectively, 0.1, 0.2, 0.3, and 0.4M; when the crosslinking times of these drug films in the TPP solution were 0, 5, 15, 30, and 60 min, the release rates attained 100, 100, 81.8, 65, and 43.3%, respectively. All the results indicated that the CS/PVA film was useful in drug delivery systems. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 808–813, 2005     

Kinetics of in vitro drug release from chitosan/gelatin hybrid membranes

In vitro studies of controlled release from chitosan/gelatin hybrid membranes were carried out using drugs of different molecular weight. It was found that release of urea, 5-fluorouracil (5-Fu), sodium benzoate, sodium salicylate, sodium mandelate, and sulfacetamide sodium followed zero-order kinetics after a short time lag. Variation of the diffusion coefficient, permeation coefficient, and degree of hydration with crosslinking and varying weight percent of gelatin in membrane matrices were studied in detail by using 5-Fu as a model drug. The diffusion coefficient and permeation coefficient of 5-Fu are dependent on the degree of hydration of the swollen membrane. The transport process of drug molecules in the hydrogel membrane is presumed to be predominantly of the pore mechanism. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 68: 1751–1758, 1998     

Polyvinyl alcohol‐polyethylene oxide‐carboxymethyl cellulose membranes for drug delivery

The purpose of this research was to develop blends of poly(vinyl alcohol) (PVA)‐poly(ethylene oxide) (PEO) and carboxymethyl cellulose (CMC) by two approaches: solvent casting and freeze‐drying to develop membranes for various biomedical applications. The PVA/PEO/CMC blends in different compositions of 90/10/20, 80/20/20, 70/30/20, 60/40/20, and 50/50/20 were prepared and were coated on polyester (PET) nonwoven fabric and were subsequently freeze‐dried (FD). The influence of PEO concentration on the blend membranes was investigated and characterized by X‐ray diffraction (XRD), differential scanning calorimetry, and attenuated total reflectance‐fourier transform infra‐red (ATR–FTIR) techniques. The water vapor transmission rate (WVTR), swelling behavior, and surface morphology of the FD membranes was also investigated. It was observed that an increase of PEO concentration in blends makes the membranes more fragile. However, the coating of this blend on PET fabric helps in developing the stable membrane. Swelling of the membranes decreased with the increase in the PEO concentration. XRD showed decrease in crystallinity with increase in concentration of PEO. Morphological studies showed a highly porous structure with interconnected pores. The total porosity of the membranes was found to be in the range 89–92%. The FD membranes were found to have WVTR in the range 2000–3000 g/m²/day. A model drug, ciprofloxacin hydrochloride was also incorporated in the matrix and drug release was studied. The antimicrobial nature of the membranes was monitored against E. coli by zone of inhibition method. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Fiber spinning from poly(propylene)–organoclay nanocomposite

SOMASIF ME C16, a filler that enables generation of anisotropic nanoparticles by in situ exfoliation of organic layered silicates, was melt compounded with poly(propylene) (PP) in the presence of maleic anhydride‐grafted PP. Fibers were prepared from this composite by a spinning procedure. The prepared anisotropic fibers were partially oriented by using different drawing ratios. The morphological study showed that the drawing ratio of the fibers particularly influences the level of exfoliation of the SOMASIF ME C16 where the nanoparticles are formed. The layered sheets of the SOMASIF particles are oriented in the direction of the fiber axis. The tensile strength of the filled fibers increases with the increase of drawing ratio much more than that of unfilled PP fibers. This result is accounted for by the formation of exfoliated structures from the nanoparticles of SOMASIF ME C16 by fiber drawing. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 604–611, 2003