Implementing polymeric pseudorotaxanes for boosting corneal permeability and antiaspergillus activity of tolnaftate: formulation development, statistical optimization, ex vivo permeation and in vivo assessment

Abstract

Fungal keratitis (FK) is a devastating ocular disease that can cause corneal opacity and blindness if not treated effectively. Tolnaftate (TOL) is a selective fungicidal drug against Aspergillus spp. which are among the most common causes of mycotic keratitis. TOL is lipophilic drug with low water solubility and permeation which act as obstacles for its clinical ocular efficacy. Hence, this study aimed to statistically optimize a novel polymeric pseudorotaxanes (PSRs) containing TOL for enhancing its ocular permeability and antifungal effect. For achieving this goal, a full 3 1 .2 2 factorial design was fashioned for preparing and optimizing TOL-PSRs using film hydration technique. Three formulation variables were studied: drug amount (X 1 ), weight ratio of Pluronics to HPβCD (X 2 ) and Pluronic system (X 3 ). Entrapment efficiency percent (EE%) (Y 1 ), particle size (PS) (Y 2 ) and zeta potential (ZP) (Y 3 ) were set as dependent variables. The selected optimal TOL-PSRs (PSR1) showed EE% of 71.55 ± 2.90%, PS of 237.05 ± 12.80 nm and ZP of −32.65 ± 0.92 mV. In addition, PSR1 was compared to conventional polymeric mixed micelles (PMMs) and both carriers significantly increased the drug flux and resulted in higher amount permeated per unit area in 8 h compared to drug suspension. The histopathological studies assured the safety of PSR1 for ocular use. The in vivo susceptibility testing using Aspergillus niger confirmed that PSR1 displayed sustained antifungal activity up to 24 h. The obtained results revealed the admirable potential of PSR1 to be used as novel nanocarriers for promoting TOL ocular delivery.

Influência do Parâmetro de Equilíbrio Hidrofílico- Hidrofóbico (HLB) dos Polímeros F98 e F127 na eficácia da formação de nanopartículas de ouro e encapsulamento do fármaco capecitabina para tratamento de câncer de estomâgo

“…A análise morfológica das nanopartículas é realizada pela técnica de microscopia eletrônica de varredura por emissão de campo (Jeol JSM-7500F), após lavagem das partículas por método de diálise (Aziz et al 2022).…”

“…Os diâmetros médios das nanopartículas serão determinados pela técnica de DLS e o potencial zeta através da mobilidade eletroforética (AZIZ et al 2022).…”

“…A adição da capecitabina é realizada após a preparação do sistema de nanopartículas de ouro e Pluronic F127 e nanopartículas de ouro e Pluronic F98, cuja quantidade utilizada é avaliada, de acordo com sua solubilização nesse sistema (AZIZ et al 2022).…”