Ciprofloxacin Loaded Nanostructured Lipid Carriers Incorporated into In-Situ Gels to Improve Management of Bacterial Endophthalmitis

摘要

Bacterial endophthalmitis (BE) is a potentially sight-threatening inflammatory reaction of the intraocular fluids or tissues caused by bacteria. Ciprofloxacin (CIP) eye drops are prescribed as first-line therapy in BE. However, frequent administration is necessary due to precorneal loss and poor ocular bioavailability. The objective of the current research was to prepare CIP containing nanostructured lipid carriers (CIP-NLCs) loaded an in situ gel system (CIP-NLC-IG) for topical ocular administration for enhanced and sustained antibacterial activity in BE treatment. CIP-NLCs were prepared by the hot homogenization method and optimized based on physicochemical characteristics and physical stability. The optimized CIP-NLC formulation was converted into CIP-NLC-IG with the addition of gellan gum as a gelling agent. Furthermore, optimized CIP-NLC and CIP-NLC-IG were evaluated for in vitro release and ex vivo transcorneal permeation studies, using commercial CIP ophthalmic solution (CIP-C) as the control. The optimized CIP-NLC formulation showed particle size, polydispersity index, zeta potential, assay and entrapment efficiency of 193.1 ± 5.1 nm, 0.43 ± 0.01, −32.5 ± 1.5 mV, 99.5 ± 5.5 and 96.3 ± 2.5%, respectively. CIP-NLC-IG with 0.2% w/v gellan gum showed optimal viscoelastic characteristics. The in vitro release studies demonstrated sustained release of CIP from CIP-NLC and CIP-NLC-IG formulations over a 24 h period. Transcorneal flux and permeability increased 4 and 3.5-fold, and 2.2 and 1.9-fold from CIP-NLC and CIP-NLC-IG formulations, respectively, when compared to CIP-C. The results demonstrate that CIP-NLC-IG could be considered as an alternate delivery system to prolong the residence time on the ocular surface after topical administration. Thus, the current CIP ophthalmic formulations may exhibit improved ocular bioavailability and prolonged antibacterial activity, which may improve therapeutic outcomes in the treatment of BE.