Novel in situ gelling ocular inserts for voriconazole-loaded niosomes: design, in vitro characterisation and in vivo evaluation of the ocular irritation and drug pharmacokinetics

Abstract

This work aimed to develop voriconazole in situ gelling ocular inserts loaded with niosomal suspension. Niosomes and mixed niosomes were prepared using span 40 and span 60 with pluronic L64 and pluronic F127. The entrapment efficiency percentages (EE%), mean vesicle size, polydispersity index (PI), zeta potential and in vitro drug release of these niosomes were evaluated. F3-mixed niosomes prepared with span 60 and pluronic L64 was selected, due to its highest EE; optimum vesicle size with smallest PdI and suitable release pattern of the drug (63% after 8 h). In situ ocular inserts were prepared using sodium carboxymethylcellulose (CMC Na) and sodium alginate (ALG) and characterised for surface morphology, surface pH, water uptake, mucoadhesion and in vitro release. ALG in situ ocular insert (S₂) was selected for further in vivo evaluation of the ocular irritation and drug pharmacokinetics in the aqueous humour of rabbit's eyes. S₂ in situ gelling ocular insert was non-irritant and showed significantly (p < 0.01) higher C_max, delayed T_max and increased bioavailability.

Keywords:

• In situ gel
• niosomes
• ocular insert
• voriconazole

Declaration of interest

The author reports no conflicts of interest. The author alone is responsible for the content and writing of the article.