Gallic acid grafting effect on delivery performance and antiglaucoma efficacy of antioxidant-functionalized intracameral pilocarpine carriers

被引:31
作者
Chou, Shih-Feng [1 ,2 ]
Luo, Li-Jyuan [1 ]
Lai, Jui-Yang [1 ,3 ,4 ,5 ]
机构
[1] Chang Gung Univ, Inst Biochem & Biomed Engn, Taoyuan 33302, Taiwan
[2] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA
[3] Chang Gung Univ, Biomed Engn Res Ctr, Taoyuan 33302, Taiwan
[4] Chang Gung Univ, Mol Med Res Ctr, Taoyuan 33302, Taiwan
[5] Chang Gung Mem Hosp, Ctr Tissue Engn, Taoyuan 33305, Taiwan
关键词
Therapeutic delivery carrier; Intracameral pilocarpine administration; Antiglaucoma effects; Antioxidant-functionalized biomaterial; Grafting amount of gallic acid; ENDOTHELIAL-CELL DENSITY; OXIDATIVE STRESS; DRUG-DELIVERY; HYALURONIC-ACID; NITRIC-OXIDE; GLAUCOMA; GELATIN; SYSTEM; RELEASE; COPOLYMERIZATION;
D O I
10.1016/j.actbio.2016.04.035
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Functionalization of therapeutic carrier biomaterials can potentially provide additional benefits in drug delivery for disease treatment. Given that this modification determines final therapeutic efficacy of drug carriers, here, we investigate systematically the role of grafting amount of antioxidant gallic acid (GA) onto GN in situ gelling copolymers made of biodegradable gelatin and thermo-responsive poly(N-isopropylacrylamide) for intracameral delivery of pilocarpine in antiglaucoma treatment. As expected, increasing redox reaction time increased total antioxidant activities and free radical scavenging abilities of synthesized carrier biomaterials. The hydrophilic nature of antioxidant molecules strongly affected physicochemical properties of carrier materials with varying GA grafting amounts, thereby dictating in vitro release behaviors and mechanisms of pilocarpine. In vitro oxidative stress challenges revealed that biocompatible carriers with high GA content alleviated lens epithelial cell damage and reduced reactive oxygen species. Intraocular pressure and pupil diameter in glaucomatous rabbits showed correlations with GA-mediated release of pilocarpine. Additionally, enhanced pharmacological treatment effects prevented corneal endothelial cell loss during disease progression. Increasing GA content increased total antioxidant level and decreased nitrite level in the aqueous humor, suggesting a much improved antioxidant status in glaucomatous eyes. This work significantly highlights the dependence of physicochemical properties, drug release behaviors, and bioactivities on intrinsic antioxidant capacities of therapeutic carrier biomaterials for glaucoma treatment. Statement of Significance Development of injectable biodegradable polymer depots and functionalization of carrier biomaterials with antioxidant can potentially provide benefits such as improved bioavailability, controlled release pattern, and increased therapeutic effect in intracameral pilocarpine administration for glaucoma treatment. For the first time, this study demonstrated that the biodegradable in situ gelling copolymers can incorporate different levels of antioxidant gallic acid to tailor the structure-property-function relationship of the intracameral drug delivery system. The systematic evaluation fully verified the dependence of phase transition, degradation behavior, drug release mechanism, and antiglaucoma efficacy on intrinsic antioxidant capacities of carrier biomaterials. The report highlights the significant role of grafting amount of gallic acid in optimizing performance of antioxidant-functionalized polymer therapeutics as new drug delivery platforms in disease treatment. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:116 / 128
页数:13
相关论文
共 54 条
[1]   Hypoglycemic effects of aqueous persimmon leaf extract in a murine model of diabetes [J].
Bae, Ui-Jin ;
Park, Soo-Hyun ;
Jung, Su-Young ;
Park, Byung-Hyun ;
Chae, Soo-Wan .
MOLECULAR MEDICINE REPORTS, 2015, 12 (02) :2547-2554
[2]   Nitric Oxide (NO): An Emerging Target for the Treatment of Glaucoma [J].
Cavet, Megan E. ;
Vittitow, Jason L. ;
Impagnatiello, Francesco ;
Ongini, Ennio ;
Bastia, Elena .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2014, 55 (08) :5005-5015
[3]   Changes in corneal endothelial cell density in patients with normal-tension glaucoma [J].
Cho, Sung Woo ;
Kim, Joon Mo ;
Choi, Chul Young ;
Park, Ki Ho .
JAPANESE JOURNAL OF OPHTHALMOLOGY, 2009, 53 (06) :569-573
[4]   Cellular lipid peroxidation end-products induce apoptosis in human lens epithelial cells [J].
Choudhary, S ;
Zhang, W ;
Zhou, F ;
Campbell, GA ;
Chan, LL ;
Thompson, EB ;
Ansari, NH .
FREE RADICAL BIOLOGY AND MEDICINE, 2002, 32 (04) :360-369
[5]   Covalent Insertion of Antioxidant Molecules on Chitosan by a Free Radical Grafting Procedure [J].
Curcio, Manuela ;
Puoci, Francesco ;
Iemma, Francesca ;
Parisi, Ortensia Ilaria ;
Cirillo, Giuseppe ;
Spizzirri, Umile Gianfranco ;
Picci, Nevio .
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2009, 57 (13) :5933-5938
[6]   MECHANISMS OF OPTIC-NERVE DAMAGE IN PRIMARY OPEN-ANGLE GLAUCOMA [J].
FECHTNER, RD ;
WEINREB, RN .
SURVEY OF OPHTHALMOLOGY, 1994, 39 (01) :23-42
[7]   ANALYSIS OF NITRATE, NITRITE, AND [N-15]-LABELED NITRATE IN BIOLOGICAL-FLUIDS [J].
GREEN, LC ;
WAGNER, DA ;
GLOGOWSKI, J ;
SKIPPER, PL ;
WISHNOK, JS ;
TANNENBAUM, SR .
ANALYTICAL BIOCHEMISTRY, 1982, 126 (01) :131-138
[8]   Potential role of nitric oxide and endothelin in the pathogenesis of glaucoma [J].
Haefliger, IO ;
Dettmann, E ;
Liu, R ;
Meyer, P ;
Prünte, C ;
Messerli, J ;
Flammer, J .
SURVEY OF OPHTHALMOLOGY, 1999, 43 :S51-S58
[9]   Controlled release of hyaluronan oligomers from biodegradable polymeric microparticle carriers [J].
Hedberg, EL ;
Shih, CK ;
Solchaga, LA ;
Caplan, AI ;
Mikos, AG .
JOURNAL OF CONTROLLED RELEASE, 2004, 100 (02) :257-266
[10]   Poly(2-hydroxyethyl methacrylate) film as a drug delivery system for pilocarpine [J].
Hsiue, GH ;
Guu, JA ;
Cheng, CC .
BIOMATERIALS, 2001, 22 (13) :1763-1769