title: An injectable thermosensitive polymeric hydrogel for sustained release of Avastin® to treat posterior segment disease.
abstract: Delivery of drugs, especially bioactive macromolecules such as proteins and nucleic acids, to the posterior segment is still a significant challenge for pharmaceutical scientists. In the present study, we developed an injectable thermosensitive polymeric hydrogel for sustained release of Avastin(®) to treat posterior segment disorders. The payload of Avastin(®) to poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) hydrogel did not influence its inherent sol-gel transition behavior, but shifted the sol-gel transition to a lower temperature. The resulting Avastin(®)/PLGA-PEG-PLGA hydrogels had a porous structure (pore size, 100 ∼ 150 μm) as determined by scanning electron microcopy (SEM), facilitating sustained Avastin(®) release over a period of up to 14 days in vitro. The PLGA-PEG-PLGA hydrogel was immediately formed in the vitreous humor after intravitreal injection, followed by slow clearance over an 8 week study period. The PLGA-PEG-PLGA hydrogel exhibited no apparent toxicity against retinal tissue, as indicated by the absence of inflammation, retinal necrosis, and stress responses, using optical coherence tomography (OCT) and histological/immunochemical analyses. Electrophysiology (ERG) examination also showed that the PLGA-PEG-PLGA hydrogel did not affect retinal function. In vivo pharmacokinetic studies indicated that the use of the PLGA-PEG-PLGA hydrogel greatly extended the release of Avastin(®) over time in the vitreous humor and retina after intravitreal injection. Together, these results demonstrated that the PLGA-PEG-PLGA hydrogel was a promising candidate for ocular drug delivery of Avastin(®)via intravitreal injection.
authors.affiliation: Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, 325027, PR China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Xie
authors.affiliation: Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, 325027, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Jin
authors.affiliation: Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, 325027, PR China; Wenzhou Institute of Biomaterials and Engineering, Wenzhou Medical University, Wenzhou, 325035, PR China.
authors.forename: Zichao
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, 325027, PR China; Wenzhou Institute of Biomaterials and Engineering, Wenzhou Medical University, Wenzhou, 325035, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, 325027, PR China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Shi
authors.affiliation: Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, 325027, PR China.
authors.forename: Zhaoliang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, 325027, PR China.
authors.forename: Meixiao
authors.initials: M
authors.lastname: Shen
authors.affiliation: Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, 325027, PR China. Electronic address: dragonhaochen@163.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, 325027, PR China. Electronic address: lixingyi_1984@163.com.
authors.forename: Xingyi
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, 325027, PR China. Electronic address: szmeyes@126.com.
authors.forename: Zongming
authors.initials: Z
authors.lastname: Song
mesh_terms: D000818:Animals; D000068258:Bevacizumab / Q000008:administration & dosage / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage / Q000737:chemistry*; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry*; D007267:Injections / Q000379:methods; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D012160:Retina / Q000378:metabolism; D013696:Temperature; D014822:Vitreous Body / Q000378:metabolism
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D011091:Polyesters; D011108:Polymers; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011100:Polyglycolic Acid; D000068258:Bevacizumab; D019344:Lactic Acid; D011092:Polyethylene Glycols
keywords: Avastin(®); Posterior segment disorder; Sustained release; Thermosensitive hydrogel