Solutol HS15 based binary mixed micelles with penetration enhancers for augmented corneal delivery of sertaconazole nitrate: optimization, in vitro, ex vivo and in vivo characterization

Abstract

Keratomycosis is a serious corneal disease that can cause a permanent visual disability if not treated effectively. Sertaconazole nitrate (STZ), a novel broad spectrum antifungal drug, was suggested as a promising treatment. However, its utility in the ocular route is restricted by its poor solubility, along with other problems facing the ocular delivery like short residence time, and the existing corneal barrier. Therefore, the objective of this study was to formulate STZ loaded binary mixed micelles (STZ-MMs) enriched with different penetration enhancers using thin-film hydration method, based on a 31.22 mixed factorial design. Different formulation variables were examined, namely, type of auxiliary surfactant, type of penetration enhancer, and total surfactants: drug ratio, and their effects on the solubility of STZ in MMs (SM), particle size (PS), polydispersity index (PDI), and zeta potential (ZP) were evaluated. STZ-MMs enhanced STZ aqueous solubility up to 338.82-fold compared to free STZ. Two optimized formulations (MM-8 and MM-11) based on the desirability factor (0.891 and 0.866) were selected by Design expert® software for further investigations. The optimized formulations were imaged by TEM which revealed nanosized spherical micelles. Moreover, they were examined for corneal mucoadhesion, stability upon dilution, storage effect, and ex vivo corneal permeation studies. Finally, both in vivo corneal uptake and in vivo corneal tolerance were investigated. MM-8 showed superiority in the ex vivo and in vivo permeation studies when compared to the STZ-suspension. The obtained results suggest that the aforementioned STZ loaded mixed micellar system could be an effective candidate for Keratomycosis-targeted therapy.

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

“…As previously mentioned, the selected TPs formulation was further optimized by incorporating stearylamine (SA) as a positive charge inducer since the positivity of the TPs would be preferred for the ocular application because it enhances electrostatic interactions with mucin (which is negatively charged), which consequently enhances retention to the corneal surface. 33 In the current study, the addition of SA did not produce a significant change ( p ˃0.05) in the EE%, PS and PDI values upon comparison with formula lacking SA ( Table 4 ). On the other hand, ZP values increased significantly ( p ˂0.05) up to 35.40±1.10 mV, which is expected to increase the vesicles stability as the chance for vesicles agglomeration will be small for charged particles having a ZP ≥30 mV (as an absolute value) due to electrostatic repulsion between them.…”

“…The particle size (PS) of the fabricated TPs is a key feature to determine their appropriateness for ocular application, since it influences their tolerance and disposition after ocular application. 33 The PS of FTN loaded TPs ranged from 233.30±2.62 to 1378.00±77.56 nm ( Table 3 ). Figure 2A shows that the terpene type (X 1 ) affected the PS of the prepared TPs significantly ( p <0.0001), where limonene showed the largest particle size TPs compared to other terpenes.…”

<p>Bilosomes as Promising Nanovesicular Carriers for Improved Transdermal Delivery: Construction, in vitro Optimization, ex vivo Permeation and in vivo Evaluation</p>

“…PDI indicates the similarity of the mixture as it becomes close to 0. 8,57 PDI of all prepared formulae varied from (0.20±0.01 to 0.43±0.01), results are presented in Table 1. These results ensure the suitable dispersion homogeneity.…”

Novel Intranasal Drug Delivery: Geraniol Charged Polymeric Mixed Micelles for Targeting Cerebral Insult as a Result of Ischaemia/Reperfusion

“…The formed thin film was hydrated with 10 mL of deionized water and sonicated (Julabo, Seelbach, Germany) at 37 • C for 15 min. Finally, geraniol MM was filtered through a 0.22-µm nylon syringe filter to remove the un-entrapped drug and stored at room temperature for 48 h in well-sealed glass vials before further characterization [27].…”