Synthesis, physicochemical properties and ocular pharmacokinetics of thermosensitive in situ hydrogels for ganciclovir in cytomegalovirus retinitis treatment

• Main Authors: Qiyue Wang, Chunmeng Sun, Bohui Xu, Jiasheng Tu, Yan Shen
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2018-01-01
• Series: Drug Delivery
• Subjects: in situ hydrogels; pbla-peg-pbla; thermosensitive; ganciclovir; intravitreal injection
• Online Access: http://dx.doi.org/10.1080/10717544.2017.1413448
• ISSN: 1071-7544; 1521-0464

Ganciclovir (GCV) is one of the most widely used antiviral drugs for the treatment of cytomegalovirus (CMV) retinitis. In this context, the aim of this study was to design in situ thermosensitive hydrogels for GCV ocular delivery by intravitreal injection to achieve sustained drug release behavior and improved ocular bioavailability in the treatment of CMV retinitis. A thermosensitive poly-(β-butyrolactone-co-lactic acid)-polyethylene glycol-poly (β-butyrolactone-co-lactic acid) (PBLA-PEG-PBLA) triblock copolymer was synthesized by ring-opening polymerization and characterization. The GCV-loaded PBLA-PEG-PBLA in situ hydrogels (15%, w/w) were then prepared with drug concentration at 2 mg·mL−1 and the gelation temperatures, rheological properties, in vitro degradation and syringeability of in situ hydrogels for intravitreal injection were also investigated. Membraneless dissolution model was used to explore drug release behavior of PBLA-PEG-PBLA in situ hydrogel. The results indicated that more than 45 and 85% of GCV can be released within 24 and 96 h, respectively, which was verified by a non-Fickian diffusion mechanism. In vivo ocular pharmacokinetics study showed that area under drug-time curve (AUC) and half-life of PBLA-PEG-PBLA in situ hydrogel was higher (AUC was 61.80 μg·mL−1·h (p < .01) and t1/2 was 10.29 h in aqueous humor; AUC was 1008.66 μg·mL−1·h (p < .01) and t1/2 was 13.26 h (p < .01) in vitreous) than GCV injection with extended therapeutic activity. Based on obtained results, it was concluded that the thermosenstive PBLA-PEG-PBLA in situ hydrogel is a promising carrier of GCV for intravitreal injection.