Tailoring thixotropic mixed-lipid nanoconstructs of voriconazole for the management of Vulvovaginal candidiasis: Formulation, statistical optimization, in vitro characterization and in vivo assessment.

Vulvovaginal candidiasis is a pervasive gynecological condition among women worldwide due to infection recurrence and resistance to conventional drugs. This calls for a novel formulation of alternative medication and with enhanced efficacy. This study aimed to fabricate mixed-lipid nanoconstructs (MLNCs) of voriconazole (VCZ) with a low concentration of lipids applying high shear homogenization and ultrasonication to form a semisolid formulation. Tefose 63 and Gelot 64 were employed as emulsifiers that are specified for vaginal preparations; as per their mucoadhesive properties and their texture enhancing characters, although usually used as lipids in different lipid carriers. A 24 factorial design was established and the optimized formulation was prepared using 10% total lipids, in which solid lipids (Sterotex NF: Glyceryl monostearate) ratio was 1.92:1 and the oils percentage was 30% (Maisine: Glyceryl monooleate, in the ratio of 1:1), and the emulsifiers mixture (Tefose 63: Gelot 64) ratio was 1:1, as 10% of total formulation weight. The optimized formulation with a viscosity of 964.49 ± 57.99 cp showed spherical nanoparticles (322.72 ± 15.11 nm) that entrapped 67.16 ± 3.45% of VCZ and exhibited release of 70.08 ± 2.87% in 8 h. The optimized formulation with high bioadhesive potentials significantly reduced the fungal burden in female Wistar rats infected with vaginal candidiasis, compared to the aqueous VCZ suspension (p < .05). Furthermore, in vivo histopathological findings proved the effectiveness and the safety of the optimized MLNCs formulation after vaginal application. Inclusively, MLNCs formulation could be a promising vaginal delivery system of VCZ for the treatment of vulvovaginal candidiasis.

Formulation and in vivo assessment of terconazole-loaded polymeric mixed micelles enriched with Cremophor EL as dual functioning mediator for augmenting physical stability and skin delivery.

The aim of the current study was to formulate terconazole (TCZ) loaded polymeric mixed micelles (PMMs) incorporating Cremophor EL as a stabilizer and a penetration enhancer. A 23 full factorial design was performed using Design-Expert® software for the optimization of the PMMs which were formulated using Pluronic P123 and Pluronic F127 together with Cremophor EL. To confirm the role of Cremophor EL, PMMs formulation lacking Cremophor EL was prepared for the purpose of comparison. Results showed that the optimal PMMs formulation (F7, where the ratio of total Pluronics to drug was 40:1, the weight ratio of Pluronic P123 to Pluronic F127 was 4:1, and the percentage of Cremophor EL in aqueous phase was 5%) had a high micellar incorporation efficiency (92.98 ± 0.40%) and a very small micellar size (33.23 ± 8.00 nm). Transmission electron microscopy revealed that PMMs possess spherical shape and good dispersibility. The optimal PMMs exhibited superior physical stability when compared with the PMMs formulation of the same composition but lacking Cremophor EL. Ex vivo studies demonstrated that the optimal PMMs formula markedly improved the dermal TCZ delivery compared to PMMs lacking Cremophor EL and TCZ suspension. In addition, it was found that the optimal PMMs exhibited a greater extent of TCZ deposition in the rat dorsal skin relative to TCZ suspension. Moreover, histopathological studies revealed the safety of the optimal PMMs upon topical application to rats. Consequently, PMMs enriched with Cremophor EL, as a stable nano-system, could be promising for the skin delivery of TCZ.

Fabrication of novel ultradeformable bilosomes for enhanced ocular delivery of terconazole: In vitro characterization, ex vivo permeation and in vivo safety assessment.

The objective of this work was to encapsulate terconazole (TCZ), a water insoluble antifungal drug, into novel ultradeformable bilosomes (UBs) for achieving enhanced ocular delivery. In addition to the constituents of the conventional bilosomes; namely, Span 60, cholesterol, and the bile salts, UBs contain an edge activator which imparts extra elasticity to the vesicles and consequently hypothesized to result in improved corneal permeation. In this study, TCZ loaded UBs were prepared utilizing ethanol injection method according to 23 full factorial design. The investigation of the influence of different formulation variables on UBs properties and selection of the optimum formulation was done using Design-Expert® software. The selected UBs formulation (UB1; containing 10mg bile salt and 5mg Cremophor EL as an edge activator) showed nanosized spherical vesicles (273.15±2.90nm) and high entrapment efficiency percent (95.47±2.57%). Results also revealed that the optimum UBs formulation exhibited superior ex vivo drug flux through rabbit cornea when compared with conventional bilosomes, niosomes, and drug suspension. Furthermore, in vivo ocular tolerance and histopathological studies conducted using male albino rabbits proved the safety of the fabricated UBs after topical ocular application. Overall, the obtained results confirmed that UBs could be promising for ocular drug delivery.