In-situ gel bases ocular delivery system of Ganciclovir, in-vivo and in-vitro investigation

作者：Susanta Paul, Subhabrota Majumdar, Mainak Chakraborty, Swarupananda Mukherjee, Nilanjan Sarkar, Bhupendra G. Prajapati, Nemat Ali, Abdullah F. Alasmari, Shamama Nishat · 发表于：BMC Pharmacology and Toxicology · 年份：2025 · DOI：10.1186/s40360-025-00934-y · 被引用次数：9 · 研究领域：Herpesvirus Infections and Treatments、Advanced Drug Delivery Systems、Ocular Surface and Contact Lens

Ocular drug delivery is challenging due to the eye's unique anatomy and physiology, which limit drug absorption and distribution. Traditional methods like eye drops have poor bioavailability and often require frequent dosing. In-situ gel systems, liquid formulations that transform into a gel upon contact with physiological conditions (pH, temperature, or ions in tear fluid), offer several advantages for ocular drug delivery. Ganciclovir was incorporated into a thermoresponsive in situ gel base. Nine formulations were prepared using the cold technique and a 3² full factorial design. The physical properties of ganciclovir gel, including clarity, pH, viscosity, gelation temperature, and gelation time, were scrutinized. In vitro drug release was assessed using a dialysis membrane method, and ocular toxicity was evaluated in a rabbit model. Poloxamer 407 and HPMC E-50 LV were used to prepare the gel, with the 3² factorial design analyzing the effects of varying concentrations on the gel's viscosity, gelation temperature, and gelation time. The optimized in-situ gel formulation (Batch B5) contained 15% w/v poloxamer 407 and 1% w/v HPMC E-50 LV, achieving a viscosity of 64.81 cPs, with a gelation temperature of 39.0 °C and a gelation time of 183 s. This formulation demonstrated better permeability and sustained ganciclovir release than a commercial formulation. Ocular toxicity studies confirmed that the formulation was non-irritating and well-tolerated. Overall, the gel showed suita...