Chitosan–Polyelectrolyte complexation for the preparation of gel beads and controlled release of anticancer drug. I. Effect of phosphorous polyelectrolyte complex and enzymatic hydrolysis of polymer

Enzymic hydrolyzed chitosan was employed to prepare chitosan–tripolyphosphate and chitosan–polyphosphoric acid gel beads using a polyelectrolyte complexation method for the sustained‐release of anticancer agent, 6‐mercaptopurine (6‐MP). pH responsive swelling ability, drug‐release characteristics, and morphology of the chitosan gel bead depends on polyelectrolyte complexation mechanism and molecular weight of the enzymic hydrolyzed chitosan. The complexation mechanism of chitosan beads gelled in pentasodium tripolyphosphate or polyphosphoric acid solution was ionotropic crosslinking or interpolymer complex, respectively. The drug‐release patterns of all chitosan gel beads in pH 6.8 seemed to be diffusional based, which might be in accordance with the Higuchi model, whereas release profiles of the chitosan–tripolyphosphate gel beads in pH 1.2 medium seemed to be non‐Fickian diffusion controlled due to the swelling or matrix erosion of the beads. The rate of 6‐MP releasing from chitosan–tripolyphosphate or chitosan–polyphosphoric acid gel matrix were significantly increased with the decreased molecular weight of enzymic hydrolyzed chitosan. However, the dissolution rates of 6‐MP entraped in chitosan–tripolyphosphate and chitosan–polyphosphoric acid gel matrix were significantly slower than the dissolution rate of the original drug. These results indicate that the chitosan–polyphosphoric acid gel bead is a better polymer carrier for the sustained release of anticancer drugs in simulated intestinal and gastric juice medium than the chitosan–tripolyphosphate gel beads. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 1868–1879, 1999     

Preparation of surface‐modified,micrometer‐sized carboxymethyl chitosan drug‐loaded microspheres

Drug‐loaded microspheres have attracted much attention in embolization therapy for liver cancer in recent years. Carboxymethyl chitosan has obvious advantages for biomedical applications because of its exceptional biocompatibility and biodegradability. In this study, surface‐modified carboxymethyl chitosan microspheres were prepared by the crosslinking reactions of carboxymethyl chitosan in a reverse suspension system with poly(ethylene glycol diglycidyl ether) (PEGDE) as the crosslinking agent; this was followed by the grafting polymerization of 2‐acrylamido‐2‐methyl propane sulfonic acid on the surface of the microspheres. The microspheres showed regular spherical shapes with size distributions ranging from 300 to 600 μm. Ion‐exchange groups (? COOH, ? SO₃H) were introduced into the microspheres; these groups could load doxorubicin with a loading rate as high as 34.6% in 24 h. This was an increase of 49.8% compared to that of the pure carboxymethyl chitosan microspheres. Additionally, the microspheres possessed large network structures because macromolecular PEGDE was used as the crosslinking agent. The drug‐release profile showed that the surface‐modified microspheres displayed a sustained‐release manner compared with the nonmodified microspheres in phosphate‐buffered saline. These microspheres have promising applications as drug‐loaded arterial embolization agents for the interventional treatment of tumors. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45731.     

A novel polymeric biomaterial based on carboxymethylstarch and its application in controlled drug release

This study reports investigation of the sustained release behavior of a model drug (acetylsalicylic acid) from carboxymethylstarch (CMS) based matrix. CMS was prepared by incorporation of carboxymethyl groups in the starch moiety; by reacting starch with sodium salt of monochloro acetic acid in presence of sodium hydroxide. The in vitro drug release study was performed by United States Pharmacopeia rotating paddle method, at various pH. The rate of drug release from the above matrix was found to increase with increase in pH. Further, the release behavior of the drug from the CMS based matrix was found to be non‐Fickian, n value being between 0.80 and 0.85, suggesting that the release was controlled by a combination of tablet erosion and diffusion of the drug from the swollen matrix. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Synthesis and characterization of polyacrylamide‐grafted chitosan hydrogel microspheres for the controlled release of indomethacin

Microspheres of polyacrylamide‐grafted‐chitosan crosslinked with glutaraldehyde were prepared and used to encapsulate indomethacin, a nonsteroidal anti‐inflammatory drug. The microspheres were produced by the water/oil emulsion technique and encapsulation of indomethacin was carried out before crosslinking of the matrix. The extent of crosslinking was analyzed by Fourier transform infrared spectroscopy and differential scanning calorimetry. Microspheres were characterized for drug‐entrapment efficiency, particle size, and water transport into the polymeric matrix as well as for drug‐release kinetics. Scanning electron microscopy confirmed the spherical nature and surface morphology of the particles with a mean particle size of 525 μm. Dynamic swelling experiments suggested that, with an increase in crosslinking, the transport mechanism changed from Fickian to non‐Fickian. The release of indomethacin depends upon the crosslinking of the network and also on the amount of drug loading. This was further supported by the calculation of drug‐diffusion coefficients using the initial time approximation. The drug release in all the formulations followed a non‐Fickian trend and the diffusion was relaxation‐controlled. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1525–1536, 2003     

An Insight on the Swelling,Viscoelastic, Electrical,and Drug Release Properties of Gelatin–Carboxymethyl Chitosan Hydrogels

The present study reports the in-depth analysis of the gelatin–carboxymethyl chitosan hydrogels. The composite system formed phase-separated hydrogels, which is confirmed by scanning electron microscopy. The swelling of the carboxymethyl chitosan-containing hydrogels was lower than the gelatin hydrogel. Macroscale deformation study using a static mechanical tester indicated a viscoelastic nature of the hydrogels. A decrease in the impedance of the hydrogels was observed with an increase in the carboxymethyl chitosan content. The drug release from the hydrogels was predominantly Fickian diffusion mediated and was released in its active form. The results suggested the potential use of the hydrogels as drug delivery matrices.     

羧甲基壳聚糖-蓖麻油基聚氨酯农药缓释微球的制备及性能

以羧甲基壳聚糖（CMCS）、蓖麻油（CO）和异佛尔酮二异氰酸酯（IPDI）为原料,自乳化法制备了羧甲基壳聚糖-蓖麻油基聚氨酯微球（CO-CMCS-PU）,通过分子自组装法负载阿维菌素（AVM）得到载药微球（CO-CMCS-PU@AVM）。采用FTIR、1HNMR、SEM、TGA等对产品结构及形貌进行表征,并探究了不同药量载药微球的包封率、缓释性能、抗紫外性能、叶面接触角和黏附性能。结果表明,相比AVM分散液,紫外照射后载药微球中AVM的保留率提高到43%,说明CO-CMCS-PU载体的抗紫外性能良好;载药微球比AVM分散液在黄瓜叶面上的接触角降低了20%以上,滞留量提高了40%以上,说明其在叶面上有较好的黏附性和润湿性;载药微球包封率可达80%以上,具有良好的缓释和pH响应释放性能,释药行为符合First-order动力学模型,药物释放受Fickian扩散控制。     

Design and optimization of alginate−chitosan−pluronic nanoparticles as a novel meloxicam drug delivery system

The inflammation and pain associated with osteoarthritis are treated with nonsteroidal anti‐inflammatory drugs (NSAIDs). This treatment is accompanied by several side effects; therefore local intra articular (IA) NSAID injection can be more efficient and safe than systemic administration or topical use. In this study, alginate?chitosan?pluronic nanoparticles were considered as a new vehicle for IA meloxicam delivery. These novel nanoparticles were prepared using an ionotropic gelation method and were optimized for variables such as alginate to chitosan mass ratio, pluronic concentration, and meloxicam concentration using a 3‐factor in 3‐level Box‐Behnken design. To optimize the formulation, the dependent variables considered were particle size, zeta potential, entrapment efficiency, and mean dissolution time (MDT). The nanoparticles morphology was characterized by FESEM and AFM. The potential interactions of the drug‐polymers were investigated by ATR‐FTIR and DSC, and the delivery profile of meloxicam from the nanoparticles was obtained. The average particle size of the optimized nanoparticles was 283 nm, the zeta potential was ?16.9 mV, the meloxicam entrapment efficiency was 55%, and the MDT was 8.9 hours. The cumulative released meloxicam amount from the composite nanoparticles was 85% at pH 7.4 within 96 h. The release profile showed an initial burst release followed by a sustained release phase. The release mechanism was non‐Fickian diffusion. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42241.     

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     

Preparation and evaluation of photocrosslinkable chitosan as a drug delivery matrix

Epichlorohydrin (1‐chloro‐2,3‐epoxypropane) was reacted with sodium azide in the presence of a phase transfer catalyst to obtain 1‐chloro‐2‐hydroxy‐3‐azidopropane, which was further coupled onto chitosan to prepare a photocrosslinkable derivative of the biopolymer. Elemental analysis and infrared (IR) spectroscopy confirmed the incorporation of azide groups onto chitosan. Films were cast from an aqueous acetic acid solution of azidated chitosan containing a model drug, such as theophylline. Irradiation of the film with ultraviolet (UV) light led to crosslinking of the drug incorporated film. IR spectra indicated complete surface crosslinking within 2 h of irradiation. Release of theophylline from uncrosslinked and crosslinked films was examined in simulated gastric and intestinal fluids without enzymes at 37 °C. The release of the drug from the crosslinked films was slower than the release from uncrosslinked films. Although the system is far from being optimized to obtain sustained release of a pharmacologically active agent for long periods, the data obtained indicate the possibility of developing photocrosslinkable matrices of biopolymers, such as chitosan, for sustained drug delivery with many advantages over chemical crosslinking. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1873–1877, 2002     

A new approach to chemically modified carboxymethyl chitosan and study of its moisture‐absorption and moisture‐retention abilities

A new approach to prepare chemically modified carboxymethyl chitosan (CM) derivatives was reported, from which initially CM was prepared from chitosan, then N‐quaternary ammonium group was introduced by the reaction of CM with 2,3‐epoxypropyl trimethylammonium. The structures of the derivatives were characterized by FTIR, XRD, ¹³C‐NMR, and gel permeation chromatography. The capability of moisture‐absorption and moisture‐retention was investigated. It was found that the moisture‐absorption and moisture‐retention ability of the new derivatives quaternized carboxymethyl chitosan (CMQ) are higher than not only that of CM but also that of chitosan quaternary (Q) and carboxymethyl group and quaternary ammonium group are in synergistic effect. Relationships between molecular structures (including degree of substitution of carboxymethylation group, degree of substitution of quaternary group, and molar mass) and functions of CMQ were also studied. The moisture absorption kinetics of CMQ was discussed and the diffusion of water molecules in it looks likely to be non‐Fickian type. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 1303–1309, 2006     

Composite films of N,O‐carboxymethyl chitosan and bamboo fiber

To obtain an antibacterial chitosan derivative, composite films of N,O‐Carboxymethyl Chitosan (N,O‐CMCS) and bamboo fiber were prepared. A water‐soluble chitosan derivative‐N,O‐CMCS was synthesized from chitosan with chloroacetic acid in alkaline solution. Composite films with 1–5 wt % N,O‐CMCS content were prepared in NaOH/urea/thiourea solution. The DS of N,O‐CMCS reached 1.70 and the water solubility increased with the increasing of DS. The carboxymethyl group was introduced into chitosan, which led to the decrease of thermal stability and crystallinity. The structural characterization confirmed that N,O‐CMCS was adsorbed on the surface of bamboo fiber. The antibacterial performance of the composite films were enhanced with the increasing of N,O‐CMCS content. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39851.     

Chitosan–polyelectrolyte complexation for the preparation of gel beads and controlled release of anticancer drug. II. Effect of pH‐dependent ionic crosslinking or interpolymer complex using tripolyphosphate or polyphosphate as reagent

Chitosangel beads were prepared using an in‐liquid curing method by ionotropic crosslinking or interpolymer linkage with tripolyphosphate (TPP) or polyphosphate (PP). The ionic interaction of chitosan with TPP or PP is pH‐dependent due to the transition of “ladder‐loop” complex structures. Chitosan gel beads cured in a pH value lower than 6 of a TPP solution was a controlled homogeneous ionic‐crosslinking reaction, whereas chitosan gel beads cured in a lower pH PP solution was a nonhomogeneous interpolymer complex reaction due to the mass‐transfer resistance for the diffusion of macromolecular PP. According to the results of FTIR and EDS studies, it was suggested that significantly increasing the ionic‐crosslinking density or interpolymer linkage of a chitosan–TPP or chitosan–PP complex could be achieved by transferring the pH value of curing agent, TPP or PP, from basic to acidic. The swelling behavior of various chitosan beads in acid medium appeared to depend on the ionic‐crosslinking density or interpolymer linkage of the chitosan–TPP or chitosan–PP complex, which were deeply affected by the in‐liquid curing mechanism of the chitosan gel beads. By the transition of the in‐liquid curing mechanism, the swelling degree of chitosan–TPP or chitosan–PP beads was depressed and the disintegration of chitosan–TPP or chitosan–PP beads did not occur in strong acid. The drug‐release patterns of the modified chitosan gel beads in simulated intestinal and gastric juices were sustained for 20 h. These results indicate that the sustained release of anticancer drugs could be achieved due to the variation of the reaction mechanism of a chitosan–polyelectrolyte pH‐dependent ionic interaction. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 1093–1107, 1999     

Encapsulation of salicylic acid in acylated low molecular weight chitosan for sustained release topical application

Acylated low molecular weight chitosan was used to encapsulate salicylic acid (SA) for sustained release in topical delivery. Chitosan nanoparticles were prepared from the depolymerization of commercial chitosan and further acylated with short alkyl chains. The successful acylation of butyryl chitosan [low molecular weight chitosan (LMWC)‐B] were proved by Fourier transform infrared (FTIR) and ¹H‐NMR. Successful encapsulation of SA was observed by the shift of amide I band from 1648 cm^?1 in LMWC‐B to 1641–1633 cm^?1 in SA‐loaded LMWC‐B in FTIR analysis, which further confirmed with the size increment from dynamic light scattering and transmission electron microscopy analyses by comparing its unencapsulated LMWC‐B. SA release from LMWC‐B studied by Franz diffusion experiment followed Korsmeyer–Peppas model where the release component n value (0.502) indicated diffusion and polymer swelling were involved in release mechanism. The slow release study of SA showed the acylated chitosan exhibited sustained release property toward SA. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134 , 45273.     

Preparation and characterization of pH‐sensitive hydrogel microspheres based on atom transfer radical polymerization

In this study, we prepared pH‐sensitive hydrogel microspheres by means of atom transfer radical polymerization of hydroxyethyl methacrylate and 4‐vinylpyridine in inverse emulsion, using poly (ethylene glycol) dimethylacrylate as a crosslinker. One‐factor experiment was used to optimize conditions of preparing microspheres and the resulting conditions were presented. The microspheres were characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis, scanning electron microscopy, and so forth. The swelling behavior of the as‐prepared microspheres was studied by a classic gravimetric method. Afterward, daidzein was used as a model drug and related release mechanism was investigated. The diffusional coefficients and the corresponding kinetic parameters of chosen mathematical models for fitting drug release were calculated, which indicated drug release accorded with anomalous (non‐Fickian) diffusion mechanism. POLYM. ENG. SCI., 55:2775–2782, 2015. © 2015 Society of Plastics Engineers     

Preparation and characterization of biomedical collagen–chitosan scaffolds with entrapped ibuprofen and silver nanoparticles

In this work, the preparation and characterization of a novel multifunctional collagen–chitosan material containing silver nanoparticles and nonsteroid anti‐inflammatory drug ibuprofen is described. As a starting material, the commercially available collagen–chitosan scaffold was used. Drug‐loading procedure was performed via supercritical CO₂‐assisted impregnation technique. Silver nanoparticles were prepared via metal vapor synthesis and introduced into the composite biopolymer matrix. An analysis of the small‐angle X‐ray scattering profiles revealed that silver nanoparticles are characterized by having a logarithmic normal size distribution with the maximum at 25 nm. The average size of particles determined from the broadening of diffraction peaks is in a good agreement with this result. The surface of the materials was characterized by X‐ray photoelectron spectroscopy. The in vitro release kinetics of ibuprofen in phosphate buffer solution with pH = 7.4 from prepared materials was studied. The drug release to solution is governed by Fickian diffusion and can be described within the Ritger–Peppas model. Introduction of silver nanoparticles has no effect on the diffusion mechanism. The as‐prepared materials are promising for the medical applications such as dressings for treatments of infected wounds and infection preventing. These materials can act as a matrix for transdermal drug administration. POLYM. ENG. SCI., 59:2479–2487, 2019. © 2019 Society of Plastics Engineers     

Release of dexamethasone from poly(N‐vinyl pyrrolidone‐co‐n‐hexyl methacrylate) copolymers of controlled hydrophilicity

A copolymer system with controlled hydrophilicity has been prepared through copolymerization technique and its capability as controlled drug release carrier is investigated. The effect of copolymer composition on water uptake, thermal properties, and morphology is reported. The water uptake increases with increasing N‐vinyl pyrrolidone content and diffusion of water molecules appears to be non‐Fickian. Dexamethasone has been selected as model drug and its controlled release from selected water stable copolymers follows for more than 1 month. Initial burst release of more than 50% occurs in 7 days. The remaining drug is released in a sustained way upto 37 days. Initial 10 h drug release pattern involves first‐order kinetics (NH73) and zero‐order kinetics (NH55), whereas initial 60% drug release mechanism appears to be non‐Fickian for NH73 (n = 0.71) and Case II transport (n = 1.24) for NH55. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2013     

On physical and antibacterial properties and drug release behavior of poly(vinyl alcohol) hydrogels: effect of drug loaded chitosan nanoparticles

This paper deals with influence of chitosan nanoparticles (CNPs) loaded by tetracycline, as a drug, on the physico-mechanical and antibacterial properties as well as drug release behavior of poly(vinyl alcohol), PVA, hydrogels prepared by electron beam irradiation. The formation of spherical chitosan particles in nanoscale size prepared by an ionic gelation method was confirmed by FTIR and UV spectroscopy, and scanning electron microscopy analyses. The drug release kinetic studies from drug loaded chitosan nanoparticles (DLCNPs) at pH = 7.4 revealed a linear and steady release behavior over long period of time. The theoretical analysis of the swelling kinetic data, using Peppas’s model showed that the swelling kinetic is governed by Fickian diffusion for all the prepared hydrogels, however, the water diffusion coefficient, and therefore, the swelling content were lower for the hydrogels loaded with DLCNPs as compared to the ones with the neat drug. In agreement with these results, the hydrogels containing DLCNPs exhibited a more controlled drug release behavior with significantly stronger antibacterial activity. The tensile mechanical properties of the hydrogels not affected by the DLCNPs were found to be suitable for wound dressing applications.     

Synthesis and evaluating of carbon nanoallotrope-biomacromolecule gel composites as drug delivery systems

This work was done to assess the role of precursors (agro and graphite) on performance of carbon nanoallotropes-biomacromolecules composite as drug delivery for controlling the release of niacin. In this respect graphene oxide and bagasse-based carbon oxide were synthesized and chelated with chitosan (Cs-GO and Cs-Co). These gel composites were characterized by many techniques [morphology, differential scanning calorimetry, Fourier-transform infrared spectroscopy, swelling, encapsulation efficiency (EE) and loading (L) % of niacin. Another series of experiments was carried out for studying the role of replacing part of carbon nanoallotrope by carboxymethyl cellulose (CMC) on performance of produced drug carries, these systems were coded as Cs-GO-CMC and Cs-Co-CMC. The data showed that, the Cs-GO gel composite provided maximum release of NA, at 5 h, for pH's simulated gastric and intestinal fluids; pH. 2.1 and pH 7.4 (1120 mg/L and 757 mg/L). The incorporation of CMC is not acceptable as it provided low drug release together with burst release of NA-drug, and consequently possible caused tissue irritation or toxicity in the human body. The Cs-GO and Cs-CO systems with relatively low drug loading were recommended for their better controllability system to NA release, which prolonging benefit of human with niacin. The NA release from all investigated gels followed Fickian and non-Fickian diffusion mechanisms.     

Interpenetrating polymeric network hydrogels for potential gastrointestinal drug release

New interpenetrating polymeric network (IPN) hydrogels based on chitosan (C), poly(N‐vinyl pyrrolidone) (PVP) and poly(acrylic acid) (PAAc), crosslinked with glutaraldehyde (G) and N,N‘‐methylenebisacrylamide (MBA), were prepared and investigated for potential gastrointestinal drug delivery vehicles utilizing a model drug, amoxicillin. IPN hydrogels were synthesized by simultaneous polymerization/crosslinking of acrylic acid monomer in the presence of another polymer (C) and crosslinker (G, MBA). Three different concentrations of glutaraldehyde were used (0.5, 1.0 and 2.0 w/w) to control the overall porosity of the hydrogels, named C‐P‐AAc/0.5, C‐P‐AAc/1.0 and C‐P‐AAc/2.0, respectively. Spectroscopic and thermal analyses such as Fourier transform infrared spectroscopy, thermogravimetric analysis and thermomechanical analysis were performed for IPN characterization. Equilibrium swelling studies were conducted for pH and temperature response behavior. Swelling studies were also carried out in simulated gastric fluid of pH = 1.1 and simulated intestinal fluid of pH = 7.4 to investigate possible site‐specific drug delivery. It was found that the release behavior of the drug from these IPN hydrogels was dependent on the pH of the medium and the proportion of crosslinker in the IPN. It was observed that amoxicillin release at pH = 7.4 was higher than at pH = 1.1. The analysis of the drug release showed that amoxicillin was released from these hydrogels through a non‐Fickian diffusion mechanism. Copyright © 2007 Society of Chemical Industry     

β‐cyclodextrin‐conjugated hyaluronan hydrogel as a potential drug sustained delivery carrier for wound healing

In order to develop a potential drug sustained delivery carrier suitable for wound healing, a series of β‐cyclodextrin conjugated hyaluronan hydrogels (β‐CD‐HA) with adjustable crosslink densities were synthesized and characterized, meanwhile the delivery kinetics and mechanism of diclofenac as a model anti‐inflammatory drug from these hydrogels were investigated. By controlling the feeding molar ratio of β‐CD/HA, a β‐CD substitution degree of 4.65% was obtained by ¹H‐NMR analysis. The incorporation of β‐CD modification had little effect on the internal porous structure, water swelling ratio, and rheological property of HA hydrogel, which however were influenced by the crosslink density. Although the crosslink density had an influence on the drug loading and release profile by altering the water swelling property, the interaction between β‐CD and drug was the primary factor for the high loading capacity and long‐term sustained delivery of diclofenac. The semiempirical equation fit showed that the release of diclofenac from HA‐based hydrogels followed a pseudo‐Fickian diffusion mechanism. By the aid of β‐CD and controlled crosslink density, a β‐CD‐HA hydrogel with a diclofenac sustained delivery period of over 28 days and desirable physicochemical properties was achieved, which will be a promising drug sustained delivery carrier for wound healing. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43072.