Triamcinolone acetonide-loaded lipid nanocapsules for ophthalmic applications

Abstract

Triamcinolone acetonide (TA) is an effective drug widely (off-label) used in the treatment of several ocular diseases involving inflammation and angiogenic processes. However, the use of TA ocular presents some limitations mainly related to its excipient composition, as in the case of benzyl alcohol. Thus, the aim of this work was to obtain an alternative TA formulation based on lipid nanocapsules (LNCs). Triamcinolone acetonide-loaded lipid nanocapsules (TA-LNCs) were obtained by the phase inversion temperature process without the use of irritating excipients, by combining lipids and surfactants generally recognized as safe. Pre-formulation studies were carried out to evaluate the TA solubility in different co-surfactants and to optimize the lipid core composition in order to enhance the drug loading and encapsulation rate in the LNCs. A stable final TA-LNC formulation was obtained with a mean particle size (MPS) of below 50 nm, a narrow size distribution (PDI < 0.2), a negative zeta potential (ZP) and a high encapsulation efficiency (%EE > 98%). In vitro cellular viability assays revealed that blank LNCs and TA-LNCs at 0.1 µg/mL did not affect the viability of the human corneal epithelial (HCE) cells. TA-LNCs showed a high anti-inflammatory activity below the toxicity level, with a reduction of 30% in interleukin (IL)-6 secretion observed in an in vitro model using the same cell line. More importantly, the TA-LNCs revealed a therapeutic efficacy in the endotoxin-induced uveitis (EIU) rabbit model with a significant attenuation of clinical signs of an inflammatory response. These findings make the TA-LNCs a safer and more efficient alternative for the treatment of eye disorders.