title: On the importance of Bloom number of gelatin to the development of biodegradable in situ gelling copolymers for intracameral drug delivery.
abstract: To overcome the drawbacks associated with conventional antiglaucoma eye drops, this work demonstrated the feasibility of an effective alternative strategy to administer pilocarpine directly via intracameral injections of drug-containing biodegradable in situ gelling GN copolymers composed of gelatin and poly(N-isopropylacrylamide). Specifically, this study aims to understand the importance of Bloom number of gelatin, a physicochemical parameter, to the development of GN carriers for intracameral drug delivery in glaucoma therapy. Our results showed that both imino acid and triple-helix contents increased with increasing Bloom index from 75-100 to 300. The drug encapsulation efficiency in response to temperature-triggered phase transition in GN copolymers was affected by the Bloom index of gelatin. In addition, the differences in protein secondary structure significantly influenced the degradation rates of GN carriers, which were highly correlated with drug release profiles. The increase in released pilocarpine concentration led to a high intracellular calcium level in rabbit ciliary smooth muscle cell cultures, indicating a beneficial pharmacological response to a drug. Irrespective of Bloom number of gelatin, all carrier materials exhibited excellent in vitro and in vivo biocompatibility with corneal endothelium. In a glaucomatous rabbit model, intracameral injections of pilocarpine-containing GN synthesized from gelatins with various Bloom numbers had different abilities to improve ocular hypertension and induce pupillary constriction, indicating distinct antiglaucoma efficacies due to in vivo drug release. It is concluded that the effects on pharmacological treatment using GN carriers for intracameral pilocarpine administration demonstrate a strong dependence on the Bloom number of gelatin.
authors.affiliation: Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan, 33302, Taiwan, ROC; Department of Bioengineering, University of Washington, Seattle, WA 98195-5061, USA.
authors.forename: Shih-Feng
authors.initials: SF
authors.lastname: Chou
authors.affiliation: Department of Chemical and Materials Engineering, Chang Gung University, Taoyuan 33302, Taiwan, ROC.
authors.forename: Li-Jyuan
authors.initials: LJ
authors.lastname: Luo
authors.affiliation: Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan, 33302, Taiwan, ROC; Biomedical Engineering Research Center, Chang Gung University, Taoyuan 33302, Taiwan, ROC; Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan, ROC; Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan, ROC; Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan, ROC. Electronic address: jylai@mail.cgu.edu.tw.
authors.forename: Jui-Yang
authors.initials: JY
authors.lastname: Lai
authors.affiliation: Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan, ROC; Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan, ROC; Department of Chinese Medicine, Chang Gung University, Taoyuan 33302, Taiwan, ROC.
authors.forename: David Hui-Kang
authors.initials: DH
authors.lastname: Ma
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods*; D005780:Gelatin / Q000008:administration & dosage / Q000378:metabolism*; D005782:Gels; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D010862:Pilocarpine / Q000008:administration & dosage / Q000378:metabolism*; D011108:Polymers / Q000008:administration & dosage / Q000378:metabolism*; D011817:Rabbits; D013552:Swine
chemical_list: D005782:Gels; D011108:Polymers; D010862:Pilocarpine; D005780:Gelatin
keywords: Biodegradable in situ gelling carrier; Bloom number; Gelatin; Glaucoma; Intracameral drug delivery; Pilocarpine