Purpose The objective of the present study was to formulate indomethacin (IN)-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) and to investigate their potential use in topical ocular delivery. Methods IN SLNs (0.1% w/v) and NLCs (0.8% w/v) were prepared, characterized and evaluated. Their in vitro release and flux profiles across the cornea and sclera-choroid-RPE (trans-SCR) tissues and in vivo ocular tissue distribution were assessed. Furthermore, chitosan chloride (CS) (mol. wt. < 200 kDa), a cationic and water-soluble penetration enhancer, was used to modify the surface of the SLNs, and its effect was investigated through in vitro transmembrane penetration and in vivo distribution tissue studies. Results For the IN-SLNs, IN-CS-SLNs and IN-NLCs, the particle size was 226 ± 5, 265 ± 8, and 227 ± 11 nm, respectively; the zeta potential was −22 ± 0.8, 27 ± 1.2, and −12.2 ± 2.3 mV, respectively; the polydispersity index (PDI) was 0.17, 0.30, and 0.23, respectively; and the entrapment efficiency (EE) was 81 ± 0.9, 91.5 ± 3.2 and 99.8 ± 0.2%, respectively. The surface modification of the SLNs with CS increased the ocular penetration of IN. The NLCs maintained significantly higher IN concentrations in all ocular tissues tested compared to the other formulations evaluated in vivo. Conclusion The results suggest that lipid-based particulate systems can serve as viable vehicles for ocular delivery. The NLC formulations demonstrated increased drug loading capability, entrapment and delivery to anterior and posterior segment ocular tissues.

Ciprofloxacin (CIP) is an antibacterial agent prescribed for the treatment of ocular infections. The objective of the present project is to investigate the effect of surface PEG functionalization of the Nano structured lipid carriers (NLCs) on formulation stability, ocular penetration and distribution. CIP NLCs were tested with different molecular weight (poly ethylene glycol) PEGs ranging from (2K to 20K) grafted onto the phospholipid and with different chain lengths (14–18 carbons) of phospholipids derivatized with PEG-2K. Drug load in the formulations was maintained at 0.3% w/v. Formulations prepared were evaluated with respect to in vitro release, transcorneal permeation, autoclavability, morphological characteristics and in vivo ocular tissue distribution. Scanning Transmission electron microscopy (STEM) studies revealed that the PEG-CIP-NLCs were spherical in shape. Transcorneal penetration of CIP was optimum with PEG molecular weight in between 2K to 10K. Carbon chain length of the phospholipid, however, did not affect transcorneal penetration of CIP. In vivo ocular tissue CIP concentrations attained from the various formulations was consistent with the in vitro data obtained. The results suggest that surface functionalization of PEGs, within a specified range of molecular weight and surface packing density, significantly enhance trans-ocular penetration and impart sterilization-stabilization characteristics into the formulations.

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.

Delivery of therapeutic molecules into the deeper ocular compartments is mainly hampered by short precorneal residence and limited transmembrane permeability of topically administered drugs. Hence, the current study was undertaken to fabricate the ion-sensitive in situ gels of natamycin (NT) bilosomes (NB) for efficient ocular delivery. The effect of cholesterol and sodium taurocholate proportion on the properties of the bilosomes were studied and the formulation with better physicochemical properties was optimized and utilized to derive the in situ gelling system (IG). The impact of type/composition of gelling agent on the formation and characteristics of the hydrogel was investigated. The hydrogel formed from IG with 0.3% w/v gellan gum showed optimal viscoelastic and adhesive characteristics. The ocular safety and cytocompatibility of NB and its IG was confirmed by corneal histology and in vitro cytotoxicity evaluation. A 6- to 9-fold enhancement in the transcorneal flux of NB demonstrated efficient ocular penetration of bilosomes. Moreover, the superior mean dose normalized NT levels in the ocular tissues of rabbits treated with optimized NB and IG illustrated the effectiveness of bilosomes loaded ion-sensitive in situ hydrogels as a potential platform for the improved and prolonged ocular pharmacotherapy.

Short precorneal residence time and poor transocular membrane permeability are the major challenges associated with topical ocular drug delivery. In the present research, the efficiency of the electrolyte-triggered sol-to-gel-forming system of natamycin (NT) transfersomes was investigated for enhanced and prolonged ophthalmic delivery. Transfersomes were optimized by varying the molar ratios of phospholipid, sorbitan monostearate (Span) and tocopheryl polyethylene glycol succinate (TPGS). NT transfersome formulations (FNs) prepared with a 1:1 molar ratio of phospholipid-to-Span and low levels of TPGS showed optimal morphometric properties, and were thus selected to fabricate the in situ gelling system. Gellan gum-based (0.3% w/v) FN-loaded formulations (FNGs) immediately formed an in situ gel in the simulated tear fluid, with considerable viscoelastic characteristics. In vitro cytotoxicity in corneal epithelial cells and corneal histology studies demonstrated the ocular safety and cytocompatibility of these optimized formulations. Transcorneal permeability of NT from these formulations was significantly higher than in the control suspension. Moreover, the ocular disposition studies of NT, from the FNs and FNGs, in New Zealand male albino rabbits demonstrated the superiority of the electrolyte-sensitive FNGs in terms of NT delivery to the ocular tissues.