Novelin situgelling ocular inserts for voriconazole-loaded niosomes: design,in vitrocharacterisation andin vivoevaluation 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 Cmax, delayed Tmax and increased bioavailability.

Amphiphilic copolymers change the nature of the ordered-to-disordered phase transition of lipid membranes from discontinuous to continuous

“…8 The L64 Pluronic in particular has demonstrated the ability to improve the drug entrapment efficiency and optimise the drug release rate in niosomes. 30 Moreover, due to the polymer's thermal sensitivity, the hybrid vesicles have shown the highest release rates in mild-hyperthermia temperatures (42 • C) and the lowest in storage temperatures (25 • C), 31 a property that is desired for drug delivery systems. Here, by analysing structural, elastic and dynamic properties at both the low temperature and the high temperature region, we will attempt to clarify the phase transformation process of a DPPC membrane and then compare it to the transformation that the DPPC/L64 bilayer undergoes.…”

How the Incorporation of Pluronic Block Copolymers Modulates the Response of Lipid Membranes to Mechanical Stress

“…29 The aim of this work is to elucidate the impact that the incorporation of Pluronic R chains has on various properties of phospholipid bilayers when the membrane is subjected to mechanical stresses. This work focuses specifically on a Pluronic R labeled as L64 (consisting of a 40% EO content and a PO molecular weight of 1800 g/mol 30 ) ( Figure 1a) which is one of the best experimentally characterized among the copolymer series [31][32][33][34][35][36][37] and shows spontaneous adsorption into phospholipid bilayers. 38 The well characterized 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid (found in abundance in mammalian cell membranes as one of their main constituents) was selected for the construction of the model lipid bilayer 39,40 (Figure 1b).…”

Voriconazole Composited Polyvinyl Alcohol/Hydroxypropyl-β-Cyclodextrin Nanofibers for Ophthalmic Delivery

“…Topical VRC can penetrate the cornea, and therapeutic concentration can be achieved in the cornea, aqueous humor and vitreous body [8, 9]. To date, no topical formulation for ocular use has become commercially available, although several attempts involving cyclodextrin based eye drop solutions and gels [10, 11], microemulsions [12], liposomes [13], and niosomes [14] have revealed the potential of VRC for topical ophthalmic administration.…”