Chitosan-coated vesicles in thermosensitive gel as a compelling platform for cannabidiol treatment of ocular disorders.

Grifoni L.; Burroni M.; Sgambellone S.; Orlandini S.; Fiani S.; Mennini N.; Tonelli M.; Furlanetto S.; Bergonzi M.; Lucarini L. et al. · International journal of biological macromolecules · 2026

**Background & Methods** This review describes the development and optimization of a novel ocular delivery system consisting of cannabidiol (CBD)-loaded chitosan-coated nanovesicles embedded in a thermosensitive poloxamer-based in situ gel (Tg-CS-VS). The formulation was optimized using multivariate design of experiments (DoE) and evaluated through in vitro cell studies and in vivo rabbit models (both normotensive and transiently hypertensive animals). **Key Findings** • The optimized Tg-CS-VS formulation achieved nanovesicles with mean diameter of 176.5 ± 6.3 nm, polydispersity index of 0.215 ± 0.022, positive ζ-potential of +24.0 ± 2.4 mV, 98.3 ± 0.5% CBD recovery, and rapid gelation time of 15 seconds at corneal temperature, demonstrating excellent physicochemical properties suitable for ocular delivery. • Mucin binding assays confirmed strong chitosan-mediated electrostatic interactions with negatively charged tear film mucins, significantly prolonging ocular residence time and promoting sustained corneal epithelial contact while transiently modulating tight junctions to enhance drug bioavailability. • In vivo studies demonstrated excellent ocular tolerability and significant intraocular pressure (IOP) reduction in both normotensive and hypertensive rabbit models, with maximal therapeutic effect observed at 60 minutes post-administration. **Dosage & Administration** Not reported. **Safety & Adverse Effects** In vitro studies using corneal keratocytes cell line demonstrated good tolerability of the formulation. In vivo studies in rabbits showed excellent ocular tolerability with no serious adverse effects reported. Specific adverse event details or quantitative safety data were not provided. **Evidence Quality** This is a review article summarizing research on a novel formulation development. The evidence base consists of preclinical in vitro and animal studies; human clinical trials have not been conducted. Limitations include reliance on rabbit models, which may not fully translate to human ocular physiology, and lack of long-term safety and efficacy data in chronic disease states. The authors acknowledge that further studies are needed to explore long-term therapeutic potential. The formulation represents an early-stage development platform with promising preliminary data but requires advancement through human trials before clinical application.

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