RESUMO
Increasing the permeability of drugs across the cornea is key to improving drug absorption by the eye. This study presents a newly developed in situ gel loaded with nanoparticles, which could achieve controlled drug release and high ocular drug bioavailability by avoiding rapid precorneal clearance. The physicochemical parameters of the formulation were investigated and showed uniform size, physical stability, and favorable rheological and gelling properties. Ex vivo permeation studies revealed significantly higher drug release from the in situ gel loaded with nanoparticles compared to the conventional poloxamer in situ gel and the drug solution. When compared with a marketed formulation, the in situ gel loaded with nanoparticles provided slower controlled release and higher ocular bioavailability of dexamethasone. In conclusion, the developed nanoparticle-loaded in situ gel can successfully increase drug ocular bioavailability by enhancing contact time with the ocular surface and permeation through the cornea.
Assuntos
Dexametasona/administração & dosagem , Dexametasona/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/administração & dosagem , Administração Oftálmica , Animais , Humor Aquoso/efeitos dos fármacos , Varredura Diferencial de Calorimetria , Córnea/efeitos dos fármacos , Preparações de Ação Retardada , Dexametasona/química , Liberação Controlada de Fármacos , Géis , Nanopartículas/química , Tamanho da Partícula , Polímeros/química , Coelhos , Reologia , Espectroscopia de Infravermelho com Transformada de Fourier , TemperaturaRESUMO
AIM: Nanostructured lipid carriers in-gel (NLCs-gel) were prepared to enhance and improve the ocular delivery of dexamethasone. Materials & methods: NLCs containing dexamethasone prepared by high-pressure homogenization were characterized and dispersed into thermosensitive gels (Pluronic F127 and F68 as gels material). In vitro drug release studies, ocular irritation tests, ex vivo corneal penetration and drug dynamics of NLCs and NLCs-gel were evaluated in aqueous humor. RESULTS: NLCs-gel exhibited a rapid sol-gel transition at 34.4°C and presented nano-sized, narrowly distributed particles. Corneal penetration studies revealed steady sustained drug release (Ritger-Peppas); NLCs-gel increased ocular bioavailability by prolonging precorneal retention time and improving corneal permeation. CONCLUSION: These findings suggest developing NLCs-gel for potential treatment of posterior segment eye diseases.
