Triamcinolone acetonide (TA), an intermediate acting corticosteroid, is used in the treatment of posterior ocular diseases, such as inflammation, posterior uveitis, and diabetic macular edema. The objective of this investigation was to prepare TA-loaded solid lipid nanoparticles (TA-SLNs) and in situ gel (TA-SLN-IG) formulations for delivery into the deeper ocular tissues through the topical route. TA-SLNs were prepared by hot homogenization and ultrasonication method using glyceryl monostearate and Compritol^® 888ATO as solid lipids and Tween^®80 and Pluronic^® F-68 as surfactants. TA-SLNs were optimized and converted to TA-SLN-IG by the inclusion of gellan gum and evaluated for their rheological properties. In vitro transcorneal permeability and in vivo ocular distribution of the TA-SLNs and TA-SLN-IG were studied using isolated rabbit corneas and New Zealand albino rabbits, respectively, and compared with TA suspension, used as control (TA-C). Particle size, PDI, zeta potential, assay, and entrapment efficiency of TA-SLNs were in the range of 200–350 nm, 0.3–0.45, −52.31 to −64.35 mV, 70–98%, and 97–99%, respectively. TA-SLN-IG with 0.3% gellan gum exhibited better rheological properties. The transcorneal permeability of TA-SLN and TA-SLN-IG was 10.2 and 9.3-folds higher compared to TA-C. TA-SLN-IG showed maximum tear concentration at 2 h, indicating an improved pre-corneal residence time, as well as higher concentrations in aqueous humor, vitreous humor and cornea at 6 h, suggesting sustained delivery of the drug into the anterior and posterior segment ocular tissues, when compared to TA-SLN and TA-C. The results, therefore, demonstrate that the lipid based nanoparticulate system combined with the in situ gelling agents can be a promising drug delivery platform for the deeper ocular tissues.

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.