An injectable thermosensitive polymeric hydrogel for sustained release of Avastin (R) to treat posterior segment disease

作者：Xie Binbin; Jin Ling; Luo Zichao; Yu Jing; Shi Shuai; Zhang Zhaoliang; Shen Meixiao; Chen Hao^*; Li Xingyi; Song Zongming

来源：International Journal of Pharmaceutics, 2015, 490(1-2): 375-383.

DOI：10.1016/j.ijpharm.2015.05.071

• Avastin (R)
• Thermosensitive hydrogel
• Sustained release
• Posterior segment disorder

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 (R) to treat posterior segment disorders. The payload of Avastin (R) 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 (R)/PLGA-PEG-PLGA hydrogels had a porous structure (pore size, 100 similar to 150 mu m) as determined by scanning electron microcopy (SEM), facilitating sustained Avastin (R) 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 (R) 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 (R) via intravitreal injection.

• 出版日期2015-7-25
• 单位温州医科大学