title: Sustained intravitreal delivery of dexamethasone using an injectable and biodegradable thermogel.
abstract: Delivery of therapeutic agents to posterior segment of the eyes is challenging due to the anatomy and physiology of ocular barriers and thus long-acting implantable formulations are much desired. In this study, a thermogelling system composed of two poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymers was developed as an injectable matrix for intravitreal drug delivery. The thermogel was prepared by mixing a sol and a precipitate of PLGA-PEG-PLGA triblock copolymers with different block ratios, among which a hydrophobic glucocorticoid, dexamethasone (DEX), was incorporated. The DEX-loaded thermogel was a low-viscous liquid at low temperature and formed a non-flowing gel at body temperature. The in vitro release rate of DEX from the thermogel could be conveniently modulated by varying the mixing ratio of the two copolymers. The long-lasting intraocular residence of the thermogel was demonstrated by intravitreal injection of a fluorescence-labeled thermogel to rabbits. Compared with a DEX suspension, the intravitreal retention time of DEX increased from a dozen hours to over 1week when being loaded in the thermogel. Additionally, intravitreal administration of the thermogel did not impair the morphology of retina and cornea. This study reveals that the injectable PLGA-PEG-PLGA thermogel is a biocompatible carrier for sustained delivery of bioactive agents into the eyes, and provides an alternative approach for treatment of posterior segment diseases.
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science, Fudan University, 220 Handan Road, Shanghai 200433, China.
authors.forename: Wenjia
authors.initials: W
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science, Fudan University, 220 Handan Road, Shanghai 200433, China.
authors.forename: Jiabin
authors.initials: J
authors.lastname: Luan
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Dongxiao
authors.initials: D
authors.lastname: Yang
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China. Electronic address: weigang@shmu.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science, Fudan University, 220 Handan Road, Shanghai 200433, China. Electronic address: yu_lin@fudan.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Yu
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Weiyue
authors.initials: W
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science, Fudan University, 220 Handan Road, Shanghai 200433, China.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Ding
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D003907:Dexamethasone / Q000008:administration & dosage* / Q000737:chemistry*; D004058:Diffusion; D004343:Drug Implants / Q000008:administration & dosage / Q000737:chemistry*; D005782:Gels / Q000737:chemistry; D058449:Intravitreal Injections / Q000379:methods; D008297:Male; D011091:Polyesters / Q000138:chemical synthesis* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry; D011817:Rabbits; D013696:Temperature; D014018:Tissue Distribution; D014822:Vitreous Body / Q000737:chemistry*
chemical_list: D004343:Drug Implants; D005782:Gels; D011091:Polyesters; C000595637:poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide); D011092:Polyethylene Glycols; D003907:Dexamethasone
keywords: Dexamethasone; Intraocular drug delivery; Intravitreal injection; Thermogel; Triblock copolymer