Cutaneous fungal infection therapy confronts several issues concerning skin permeation in addition to drug resistance and adverse effects of conventional drugs. The repurposing strategy is supposed to overcome some of those therapeutic obstacles. Recently, atorvastatin (ATO) revealed antifungal activity. ATO is an antihyperlipidemic drug with pH-dependent solubility, which limits skin permeation. This study aims to improve ATO antifungal activity by encapsulation in an emulsomes (EMLs) system, which seeks to ameliorate skin penetration. Therefore, multiple factors were investigated according to the One-Factor-at-a-Time (OFAT) design to achieve the optimum formula with targeted characteristics. Minimizing particle-size and polydispersity-index, besides elevating zeta-potential (ZP) and entrapment-efficiency were the desirable responses during assessing 11 factors. The selected ATO-EMLs formula (E21) recorded 250.5 nm in particle size, polydispersity index of 0.4, ZP of –25.93 mV, and 83.12% of drug entrapped. Morphological study of E21 revealed spherical core–shell vesicles in nanosize. DSC, XRD, and FTIR were conducted to discover the physicochemical properties and confirm emulsomes formation. Optimized ATO-EMLs slowed drug release rate as only 75% of ATO was released after 72 h. Stability study recommended storage between 2 and 8 °C. The in vivo permeation study remarked a homogeneous penetration of EMLs in different skin layers. The in vivo skin irritation test revealed limited histopathological changes. The in vitro and in vivo microbiological studies demonstrated a good antifungal activity of ATO-EMLs. ATO-EMLs system improved antifungal activity as the MIC values reduced from 650 µg/mL for free ATO to 550 µg/mL for ATO-EMLs. These findings may shed light on ATO as an antifungal drug and nanosystems as a tool to support drug repurposing.

Dermal fungal infection faces many challenges, especially for immunocompromised patients. Recently, the repositioning of atorvastatin (ATO) as a promising anti-mycoses therapy is used to overcome some issues of conventional therapeutic agents such as microbial resistance. The goal of this study was to develop a suitable formula for dermal fungal infection. Wherefore, ATO was entrapped into emulsomes and then incorporated in a foam system for topical convenient application. The D-optimal design was used for the optimization of ATO-emulsome and foam to achieve suitable responses. Regarding emulsomes, cholesterol weight and sonication time were independent variables that impact emulsome size, polydispersity index, surface charge, and entrapment efficiency. The optimum formula showed a size of 359.4 ± 8.97 nm, PDI of 0.4752 ± 0.012, a zeta potential of −21.27 ± 0.53 mV, and a drug entrapment of 95 ± 2.38%. Transmission electron microscope and Fourier-transform infrared spectroscopy (FT-IR) proved the assembly of ATO-emulsome. Foam composition was optimized to achieve good expansion, stability, and viscosity using a surfactant triple mixture and hydroxypropyl methylcellulose. The selected ATO-emulsome foam which consisted of 1% HPMC, 1.249% SDS, and 4% pluronic showed prolonged drug release. Efficient permeation through skin layers was asserted by using a confocal laser scanning microscope. Moreover, the homogenous distribution of the foam bubbles upholds stability and conserves the system from rapid collapse. The antifungal activity was confirmed by an in-vitro and in-vivo microbiology study beside in-vivo biocompatibility. In conclusion, ATO-emulsome and incorporation in foam have demonstrated good antifungal activity which presented a unique aspect for potential clinical applications.

Amlodipine besylate (AML) is a renowned antihypertensive drug currently acknowledged for having antibacterial activity. AML repositioning can be helpful in the defeat of microbial-resistant strains. Loading amlodipine in the pluroleosomes (PLOs) foam system is desired to approach innovative remedies with a convenient application capable of targeting deep infections. The mixture design was employed to generate different pluroleosomes formulations consisting of various ratios of Pluronic F-127, oleic acid, and soya lecithin loaded with amlodipine. Based on the desirability function, the selected optimized formula (AML-PLOs), consisting of 4.875 for lecithin, one for oleic acid, and 1.125 for pluronic, exhibits a particle size of 320.56 ± 15.5 nm, a polydispersity index of 0.4461 ± 0.03, a surface charge of 15.261 ± 0.62 mV, and AML entrapment of 71.25 ± 3.52 %. The morphological image displayed a uniform spherical shape at the nanoscale. In addition, thermal analysis and infrared spectroscopy (IR) proved the suitability of AML-pluroleosome vesicles. Tween 20, the selected nonionic surfactant in foam preparation, achieved the demand values of foam parameters and showed adequate stability upon storage for up to 90 days. The selected AML-PLO foam showed complete AML release after 48 h in a controlled manner, and the cumulative amount permeated after 24 h was about 45 %. Efficient penetration through dermal strata was affirmed by utilizing a confocal microscope. In vitro microbiological assay, besides the in vivo microbiological and histopathological studies employing a wound healing model, validated the antibacterial efficacy of amlodipine. Those outcomes demonstrated that the prepared pluroleosome foam system of AML is a competent candidate for combating topical bacterial infection.

Background: Amlodipine besylate (AML) is recognized as a calcium channel blocker curative for hypertension. However, the drug emerged recently as an antibacterial cure that competently prevails over resistant strains. Methods: Incorporating amlodipine into zein nanoparticles was employed to innovate a suitable carrier for loading and targeting deep corneal infection. The Box–Behnken design was adopted to produce various formulations of amlodipine-loaded zein nanoparticles (AML-ZNs) with diversity in composition concentration (% w/v), comprising zein, Labrafac, and poloxamer 407. Results: Relying on the optimization criterion, the chosen preference formulation concentration (% w/v) consists of 2.068 for zein, 0.75 for Labrafac, and 1.0 for Poloxamer. Morphological micrography of AML-ZNs showed regular spherical particles in the nanometric scale, and physicochemical characterization procedures confirmed system suitability. While tracking eyedrop optimum features, sodium alginate was selected for coating nanoparticles to improve stability and system viscosity. Both pH and sterility were also considered and maintained. Comparative studies were conducted pre- and post-coating, and the assessed features for the final selected formulation were 349.9 ± 5.8 nm, 0.2186 ± 0.0271, −55.45 ± 1.84 mV, 81.293 ± 0.9%, and 19.3 ± 0.19 cp for size, PDI, surface charge, entrapment, and viscosity, respectively. The AML-ZNs-Alg formulation demonstrates a more controlled pattern of release of roughly 40% of the drug released after 48 h, while the permeation profile shows 37 ± 3.52% permeated after 24 h, confirmed visually. In vitro microbial assay alongside the corneal in vivo microbial and histological pathology evaluation proved the efficacy of amlodipine as an antibacterial agent. Conclusions: These findings highlighted that the prepared AML-ZNs-Alg eyedrop can be a promising system as an antibacterial therapy.