In this research, a novel drug delivery system consisting of alginate microspheres and carboxymethyl chitosan/poly(vinyl alcohol) hydrogel was developed for prolonged and sustained controlled drug release. The alginate microspheres and various volume ratios of carboxymethyl chitosan were incorporated physically into poly(vinyl alcohol) to form the composite system. Scanning electron microscope, rheometer, differential scanning calorimetry, and thermogravimetric analysis were used to investigate the morphological, rheological, and thermal properties. The adsorptivity and hydrogel content were evaluated by swelling ratio and gel fraction, respectively. Incorporation of alginate microspheres improved the swelling ratio and thermal stability of carboxymethyl chitosan/poly(vinyl alcohol) hydrogel. Carboxymethyl chitosan decreased gel fraction and elasticity while increased swelling and porosity of hydrogel. In vitro, the release profiles of bovine serum albumin from the composite gels were sustained for 2 weeks in phosphate buffered saline.
ZhangXZJo LewisPChuCC. Fabrication and characterization of a smart drug delivery system: microsphere in hydrogel. Biomaterials2005; 26: 3299–3309.
2.
BhattaraiNGunnJZhangM. Chitosan-based hydrogels for controlled, localized drug delivery. Adv Drug Deliv Rev2010; 62: 83–99.
3.
HeCKimSWLeeDS. In situ gelling stimuli-sensitive block copolymer hydrogels for drug delivery. J Control Release2008; 127: 189–207.
4.
SlowingIIVivero-EscotoJLWuCW. Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers. Adv Drug Deliv Rev2008; 60: 1278–1288.
5.
LeeJLeeKY. Injectable microsphere/hydrogel combination systems for localized protein delivery. Macromol Biosci2009; 9: 671–676.
6.
OhJKDrumrightRSiegwartDJ. The development of microgels/nanogels for drug delivery applications. Prog Polym Sci2008; 33: 448–477.
7.
ZhaoXHarrisJM. Novel degradable poly(ethylene glycol) hydrogels for controlled release of protein. J Pharm Sci1998; 87: 1450–1458.
8.
BajpaiAKShuklaSKBhanuS. Responsive polymers in controlled drug delivery. Prog Polym Sci2008; 33: 1088–1118.
9.
StammenJAWilliamsSKuDN. Mechanical properties of a novel PVA hydrogel in shear and unconfined compression. Biomaterials2001; 22: 799–806.
10.
LeeKYYukSH. Polymeric protein delivery systems. Prog Polym Sci2007; 32: 669–697.
11.
GuoBLGaoQY. Preparation and properties of a pH/temperature-responsive carboxymethyl chitosan/poly(N-isopropylacrylamide)semi-IPN hydrogel for oral delivery of drugs. Carbohydr Res2007; 342: 2416–2422.
12.
FanLDuYZhangB. Preparation and properties of alginate/carboxymethyl chitosan blend fibers. Carbohydr Poly2006; 65: 447–452.
13.
ChenLTianZDuY. Synthesis and pH sensitivity of carboxymethyl chitosan-based polyampholyte hydrogels for protein carrier matrices. Biomaterials2004; 25: 3725–3732.
14.
ChenSCWuYCMiFL. A novel pH-sensitive hydrogel composed of N,O-carboxymethyl chitosan and alginate cross-linked by genipin for protein drug delivery. J Control Release2004; 96: 285–300.
15.
ZhaoLZhuBJiaY. Preparation of biocompatible carboxymethyl chitosan nanoparticles for delivery of antibiotic drug. Biomed Res Int2013; 2013: 236469.
16.
LinYHLiangHFChungCK. Physically crosslinked alginate/N,O-carboxymethyl chitosan hydrogels with calcium for oral delivery of protein drugs. Biomaterials2005; 26: 2105–2113.
17.
ShiBShenZZhangH. Exploring N-imidazolyl-O-carboxymethyl chitosan for high performance gene delivery. Biomacromolecules2012; 13: 146–153.
18.
WangLCChenXGZhongDY. Study on poly(vinyl alcohol)/carboxymethyl-chitosan blend film as local drug delivery system. J Mater Sci Mater Med2007; 18: 1125–1133.
19.
WangLCChenXGXuQC. Plasma protein adsorption pattern and tissue-implant reaction of poly(vinyl alcohol)/carboxymethyl-chitosan blend films. J Biomater Sci Polym Ed2008; 19: 113–129.
20.
ZhangFChengGYingX. Emulsion and macromolecules templated alginate based polymer microspheres. React Funct Polym2006; 66: 712–719.
21.
HoriYWinansAMIrvineDJ. Modular injectable matrices based on alginate solution/microsphere mixtures that gel in situ and co-deliver immunomodulatory factors. Acta Biomater2009; 5: 969–982.
22.
MiaoTRaoKSSpeesJL. Osteogenic differentiation of human mesenchymal stem cells through alginate-graft-poly(ethylene glycol) microsphere-mediated intracellular growth factor delivery. J Control Release2014; 192: 57–66.
23.
LinHRSungKCVongWJ. In situ gelling of alginate/pluronic solutions for ophthalmic delivery of pilocarpine. Biomacromolecules2004; 5: 2358–2365.
24.
LiuZLiJNieS. Study of an alginate/HPMC-based in situ gelling ophthalmic delivery system for gatifloxacin. Int J Pharm2006; 315: 12–17.
25.
LeeJHRyuMYBaekHR. The effects of recombinant human bone morphogenetic protein-2-loaded tricalcium phosphate microsphere-hydrogel composite on the osseointegration of dental implants in minipigs. Artif Organs2014; 38: 149–158.
26.
ZhuAMHua ChenJLiuQL. Controlled release of berberine hydrochloride from alginate microspheres embedded within carboxymethyl chitosan hydrogels. J Appl Polym Sci2011; 120: 2374–2380.
27.
LiuWGriffithMLiF. Alginate microsphere-collagen composite hydrogel for ocular drug delivery and implantation. J Mater Sci Mater Med2008; 19: 3365–3371.
28.
ShenJBurgessDJ. Accelerated in vitro release testing of implantable PLGA microsphere/PVA hydrogel composite coatings. Int J Pharm2012; 422: 341–348.
29.
KimSEParkJHChoYW. Porous chitosan scaffold containing microspheres loaded with transforming growth factor-beta1: implications for cartilage tissue engineering. J Control Release2003; 91: 365–374.
30.
YangYTangGZhangH. Controllable dual-release of dexamethasone and bovine serum albumin from PLGA/beta-tricalcium phosphate composite scaffolds. J Biomed Mater Res B Appl Biomater2011; 96: 139–151.
31.
JaklenecAWanEMurrayME. Novel scaffolds fabricated from protein-loaded microspheres for tissue engineering. Biomaterials2008; 29: 185–192.
32.
ZuoQLuJHongA. Preparation and characterization of PEM-coated alginate microgels for controlled release of protein. Biomed Mater2012; 7: 035012.
33.
LiuZJiaoYZhangZ. Calcium-carboxymethyl chitosan hydrogel beads for protein drug delivery system. J Appl Polym Sci2007; 103: 3164–3168.
34.
HassanCMPeppasNA. Structure and morphology of freeze-thawed PVA hydrogels. Macromolecules2000; 33: 2472–2479.
35.
SungJHHwangMRKimJO. Gel characterisation and in vivo evaluation of minocycline-loaded wound dressing with enhanced wound healing using polyvinyl alcohol and chitosan. Int J Pharm2010; 392: 232–240.
36.
Abdel-MohsenAMAlyASHrdinaR. Eco-synthesis of PVA/chitosan hydrogels for biomedical application. J Polym Environ2011; 19: 1005–1012.
37.
SabaaMWMohamedRREltaweelSH. Crosslinked poly(vinyl alcohol)/carboxymethyl chitosan hydrogels for removal of metal ions and dyestuff from aqueous solutions. J Appl Polym Sci2012; 123: 3459–3469.
38.
XuDAsaiDChilkotiA. Rheological properties of cysteine-containing elastin-like polypeptide solutions and hydrogels. Biomacromolecules2012; 13: 2315–2321.
39.
CarusoMMDavisDAShenQL. Mechanically-induced chemical changes in polymeric materials. Chem Rev2009; 109: 5755–5798.
40.
LeoneGConsumiMGrecoG. A PVA/PVP hydrogel for human lens substitution: synthesis, rheological characterization, and in vitro biocompatibility. J Biomed Mater Res B Appl Biomater2011; 97: 278–288.
41.
AbdelrazekEMElashmawiISLabeebS. Chitosan filler effects on the experimental characterization, spectroscopic investigation and thermal studies of PVA/PVP blend films. Physica B2010; 405: 2021–2027.
ZhaoLMitomoHZhaiM. Synthesis of antibacterial PVA/CM-chitosan blend hydrogels with electron beam irradiation. Carbohydr Poly2003; 53: 439–446.
44.
CasconeMGMaltintiSBarbaniN. Effect of chitosan and dextran on the properties of poly(vinyl alcohol) hydrogels. J Mater Sci Mater Med1999; 10: 431–435.
45.
KitturFSHarish PrashanthKVSankarKU. Characterization of chitin, chitosan and their carboxymethyl derivatives by differential scanning calorimetry. Carbohydr Poly2002; 49: 185–193.
46.
XuCXChenRYZhengX. Preparation of PVA-GA-CS/PVA-Fe-SA bipolar membrane and its application in electro-generation of 2,2-dimethyl-3-hydroxypropionic acid. J Membrane Sci2008; 307: 218–224.
47.
KimJOParkJKKimJH. Development of polyvinyl alcohol-sodium alginate gel-matrix-based wound dressing system containing nitrofurazone. Int J Pharm2008; 359: 79–86.
