Thermosensitive PEG-PCL-PEG (PECE) hydrogel as an in situ gelling system for ocular drug delivery of diclofenac sodium.
Development of efficient ocular drug delivery systems was still a challenging task. The objective of this article was to develop a thermosensitive PEG-PCL-PEG (PECE) hydrogel and investigate its potential application for ocular drug delivery of diclofenac sodium (DIC). PECE block polymers were synthesized by coupling MPEG-PCL co-polymer using IPDI reagent, and then its sol-gel transition as a function with temperature was investigated by a rheometer. The results showed that 30% (w/v) PECE aqueous solution exhibited sol-gel transition at approximately 35 °C. In vitro release profiles showed the entrapped DIC was sustained release from PECE hydrogels up to 7 days and the initial drug loading greatly effect on release behavior of DIC from PECE hydrogels. MTT assay results indicated that no matter PECE or 0.1% (w/v) DIC-loaded PECE hydrogels were nontoxic to HCEC and L929 cells after 24 h culturing. In vivo eye irritation test showed that the instillation of either 30% (w/v) PECE hydrogels or 0.1% (w/v) DIC-loaded PECE hydrogels to rabbit eye did not result in eye irritation within 72 h. In vivo results showed that the AUC0-48 h of 0.1% (w/v) DIC-loaded PECE hydrogels exhibited 1.6-fold increment as compared with that of commercial 0.1% (w/v) DIC eye drops, suggesting the better ophthalmic bioavailability could be obtained by the instillation of 0.1% (w/v) DIC-loaded PECE hydrogels.
a Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye hospital, Wenzhou Medical University , Wenzhou , China.
Zichao
Z
Luo
a Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye hospital, Wenzhou Medical University , Wenzhou , China.
Ling
L
Jin
a Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye hospital, Wenzhou Medical University , Wenzhou , China.
Lu
L
Xu
a Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye hospital, Wenzhou Medical University , Wenzhou , China.
Zhao Liang
ZL
Zhang
a Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye hospital, Wenzhou Medical University , Wenzhou , China.|b Wenzhou Institute of Biomaterials and Engineering , Wenzhou , China.
Jing
J
Yu
a Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye hospital, Wenzhou Medical University , Wenzhou , China.
Shuai
S
Shi
a Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye hospital, Wenzhou Medical University , Wenzhou , China.
Xingyi
X
Li
a Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye hospital, Wenzhou Medical University , Wenzhou , China.|b Wenzhou Institute of Biomaterials and Engineering , Wenzhou , China.
Hao
H
Chen
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001082:Aqueous Humor / Q000378:metabolism; D001682:Biological Availability; D002470:Cell Survival / Q000187:drug effects; D004008:Diclofenac / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005123:Eye / Q000187:drug effects; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D007509:Irritants; D008297:Male; D009883:Ophthalmic Solutions; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011817:Rabbits; D012995:Solubility
D000894:Anti-Inflammatory Agents, Non-Steroidal; D020100:Hydrogels; D007509:Irritants; D009883:Ophthalmic Solutions; D011091:Polyesters; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); C502908:poly(ethylene glycol)-poly(caprolactone)-poly(ethylene glycol); D004008:Diclofenac; D011092:Polyethylene Glycols
In situ gelling system; ocular drug delivery; thermosensitive hydrogel