Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 570, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2019.118688
Keywords
Thermosensitive hydrogel; In situ gelling system; Ophthalmic drug delivery; Ocular irritation
Categories
Funding
- Zhejiang Provincial Natural Science Foundation of China [LR18H300002]
- Zhejiang Medicines Health Science and Technology Program [WKJ-ZJ-1529]
- National Natural Science Foundation of China [31671022]
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In the present study, we developed and evaluated an in situ gelling system based on hexanoyl glycol chitosan (H-GCS) for enhanced ocular bioavailability. An aqueous solution of H-GCS exhibited a typical sol-gel transition at 32 degrees C. The formed H-GCS hydrogel was characterized by rheology and scanning electron microscopy (SEM). H-GCS had minimal in vitro cytotoxicity against L-929 and HCEC cells over a concentration range of 0-0.8 mg/mL. Additionally, the H-GCS hydrogel exhibited good ocular tolerance and biocompatibility after a single instillation. Moreover, H-GCS hydrogel significantly prolonged the precorneal retention of fluorescein sodium compared with its aqueous solution. An in vivo pharmacokinetic study demonstrated that the levofloxacin-loaded H-GCS hydrogel could provide a significantly higher C-max and AUC(0-12h) compared with the levofloxacin aqueous solution, thus increasing ocular bioavailability. Overall, the proposed H-GCS hydrogel acts as an in situ gelling system that might represent a promising vehicle for topical ocular drug delivery.
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