Besifloxacin nanostructured lipid carrier containing for the treatment ophthalmic infections: preparation, physicochemical and biological characterization in vitro and in vivo

• Ano de defesa: 2023
• Autor(a) principal: Henostroza, Mirla Anali Bazan
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: eng
• Instituição de defesa: Biblioteca Digitais de Teses e Dissertações da USP
• Palavras-chave em Português: Atividade antimicrobiana in vitro; Besifloxacin; Besifloxacino; Carreador lipídico nanoestruturado (CLN); Citotoxicidade; Cytotoxicity; Estabilidade; In vitro antimicrobial activity; Nanostructured lipid carrier (NLC); Stability
• Link de acesso: https://www.teses.usp.br/teses/disponiveis/9/9139/tde-08032024-162552/

Conjunctivitis, keratitis, and blepharitis are the most frequent ophthalmic infections caused mainly by bacteria. Conventional treatment consists of topical administration of broad-spectrum antibiotics. Due to ocular barriers, topical treatment requires high doses and repeated administrations to achieve a therapeutic effect. Besifloxacin, a new generation of fluoroquinolone, indicated exclusively for the topical treatment of ophthalmic infections, has low solubility in water. This characteristic limit its bioavailability and predisposes it to the development of resistance. Thus, innovative approaches are needed in the development of antibiotic containing eye drops. Nanostructured lipid carrier (NLC) may present innovative properties attributed to the nanometric scale. This project\'s objective was to prepare and evaluate the physicochemical and biological characteristics of NLC containing besifloxacin (BFX-NLC) for ophthalmic use. Solid and liquid lipid selection was carried out using the saturation method. NLCs were prepared by the high-pressure homogenization method. BFX showed higher solubility in capric/caprylic acid triglycerides and Softisan®154 among the liquid and solid lipids tested. The optimized BFX-NLC showed Z-aveof 93.6 ± 1.7 nm and a polydispersion index (PDI) equal to 0.15 ± 1.7. The physical stability showed no change in Z-ave and IP for nine months, at 30 ± 2 °C and 75 ± 5 % relative humidity. BFX-NLC showed 50% of drug release after 12 h. The in vitro antimicrobial activity demonstrated that the preparation method does not compromise the antimicrobial efficacy of BFX. Additionally, BFX-NLC did not show toxicity in Galleria mellonella larvae. These findings may foster an innovative platform for treating ophthalmic bacterial infections with larger interval between administrations compared to the conventional preparation.