Thermosensitive chitosan-coated liposome-based gel for ocular delivery of cannabidiol: development, characterization, and in vivo evaluation

Cannabidiol (CBD) is a non-psychoactive phytocannabinoid with known anti-inflammatory and neuroprotective properties. However, its therapeutic potential is limited by poor solubility, low bioavailability, and chemical instability. In this study, we developed an innovative ocular formulation for topical administration of CBD, based on chitosan-coated liposomes (LP-CBD) incorporated into a thermosensitive Poloxamer 407-based gel (Tg-LP-CBD). The lead formulation was optimized using a Quality by Design approach. LP-CBD and Tg-LP-CBD were characterized through TEM imaging, dynamic and electrophoretic light scattering measurements, chemical stability (R%), and mucin interaction studies. The gel exhibited pseudoplastic behavior, appropriate syringeability, and chemical stability for up to four weeks. In vivo tolerance was assessed in New Zealand White rabbits over a 7-day period, demonstrating safety for both the empty and CBD-loaded systems at a concentration of 0.05% w/v. In normotensive and transient ocular hypertension rabbit models, topical administration of 30 μL of gel LP-CBD significantly reduced intraocular pressure (IOP), with a maximal effect observed between 60 and 120 minutes post-treatment. The CBD-loaded system showed a faster and more pronounced IOP-lowering effect compared to the empty carrier, confirming the pharmacological activity of the formulation.