Formulation Development and Permeation Studies of Vancomycin Hydrochloride-Loaded Nanostructured Lipid Carrier Incorporated Thermoresponsive In-Situ Gel: A Box-Behnken Design Implemented Approach for Ocular Delivery in Endophthalmitis.

Abstract

Background: Endophthalmitis, an inflammatory condition of the intraocular cavity, poses a significant challenge in ophthalmology due to its rapid progression and potential for vision loss. Conventional treatment modalities, such as systemic antibiotics or oral administration, often face limitations in achieving the required therapeutic levels at the target site. Hence, repeated intravitreal injections of antibiotics are currently the most preferred and recommended therapy for the management of endophthalmitis, which is an invasive technique and has certain shortcomings, elevated intraocular pressure, bleeding inside the eye, heightened likelihood of retinal detachment, retinal toxicity, and many more. Vancomycin is the first choice drug for the management of endophthalmitis and is given through intravitreal injection.

Aim: The work aims to design, develop, and evaluate Vancomycin-loaded NLCs incorporated into an in-situ gel offering a new non-invasive therapeutic option for the management of Endophthalmitis.

Method: The Vancomycin-loaded NLCs were successfully produced through a double emulsion/ solvent evaporation method employing a Box Behnken design. The optimized formulations were incorporated into an in-situ gel system by varying the concentration of Pluronic F127. The formulated gels were characterized for several parameters such as physical appearance, pH, viscosity, gelling strength, gelation temperature, in vitro release profile, and ex-vivo permeation study.

Results: The result revealed that the formulation had a smooth appearance with a pH range from 7 to 7.5, was near the physiological pH of the eye, had content in the range of 97.5 ± 1.0 %to 99.2 ± 1.0 % and gelation temperature near body temperature. The data of release study formulation (VISG2) revealed sustained drug release compared to the control gel. The data ex vivo permeation study revealed that there was approximately a 3 folds increase in permeation of drug form (VISG2) compared to control gel (p˂0.0001) and significant (2.02folds) permeation compared to commercially available formulation (p˂0.0001).

Conclusion: In conclusion, the Vancomycin-loaded NLCs incorporated in-situ gel may serve as a feasible alternative to invasive intravitreal injection for the management of endophthalmitis.