Ultra-deformable liposomes containing terpenes (terpesomes) loaded fenticonazole nitrate for treatment of vaginal candidiasis: Box-Behnken design optimization, comparative ex vivo and in vivo studies

Abstract

Fenticonazole nitrate (FTN) is a potent antifungal drug adopted in the treatment of vaginal candidiasis. It has inadequate aqueous solubility hence, novel ultra-deformable liposomes ‘Terpesomes’ (TPs) were developed that might prevail over FTN poor solubility besides TPs might abstain the obstacles of mucus invasion. TPs were assembled by thin-film hydration then optimized by Box Behnken design utilizing terpenes ratio (X 1 ), sodium deoxycholate amount (X 2 ), and ethanol concentration (X 3 ) as independent variable, whereas their impact was inspected for entrapment efficiency (Y 1 ), particle size (Y 2 ), and polydispersity index (Y 3 ). Design Expert ® was bestowed to select the optimal TP for more studies. The optimal TP had entrapment efficiency of 62.18 ± 1.39%, particle size of 310.00 ± 8.16 nm, polydispersity index of 0.20 ± 0.10, and zeta potential of −10.19 ± 0.2.00 mV. Elasticity results were greater in the optimal TP related to classical bilosomes. Further, ex vivo permeation illustrated tremendous permeability from the optimal TP correlated to classical bilosomes, and FTN suspension. Besides, in vivo assessment displayed significant inhibition effect in rats from FTN-TPs gel compared to FTN gel. The antifungal potency with undermost histopathological variation was detected in rats treated with FTN-TPs gel. Overall, the acquired findings verified the potency of utilizing FTN-TPs gel for treatment of vaginal candidiasis.

Development and Optimization of Terpene-Enriched Vesicles (Terpesomes) for Effective Ocular Delivery of Fenticonazole Nitrate: In vitro Characterization and in vivo Assessment

“… 15 The particle size (PS) and the entrapment efficiency (EE%) were the selected CQAs that can significantly affect the quality and efficacy of the developed TPs. Based on literature review 16–19 and preliminary screening experiments (data is not shown), risk assessment was implemented to identify the process parameters that may potentially affect the CQAs of FTN-loaded TPs. In the current study, terpene type (X 1 ) and amount (X 2 ) were identified as the highest formulation risk factors affecting the CQAs of TPs.…”

“… 11 The receptor medium was 50 mL of phosphate buffer saline solution (pH 7.4) containing 25% ethanol to maintain the sink condition. 16 Aliquots were removed at 1, 2, 3, 4, 5 and 6 hours. Samples were analyzed by UV spectrophotometer at λ max 252 nm.…”

Fenticonazole nitrate loaded trans-novasomes for effective management of tinea corporis: design characterization, in silico study, and exploratory clinical appraisal

“…Hence, FTN is thought to be a promising topical agent for treating skin fungal infections. Unfortunately, the low aqueous solubility of FTN (<0.10 mg/mL) (Albash et al., 2020 ) arouses the need for designing a new vesicular system to deliver FTN effectively and compel cure of fungal infections.…”

Development and Optimization of Nanolipid-Based Formulation of Diclofenac Sodium: In Vitro Characterization and Preclinical Evaluation

“…The experimental value of all prepared DC-BMs was applied into experimental design model and best fit model was found linear for vesicle size and 2nd order (2F1) model for EE. The adequate precision for VS and EE found >4 and represents model as well fitted [ 27 ]. The predicted R 2 values were found to be closer to adjusted R 2 and statistical analysis expressed in Table 2 .…”