Tacrolimus-Loaded Solid Lipid Nanoparticle Gel: Formulation Development and In Vitro Assessment for Topical Applications.

Abdul Shakur Khan,Abdulkhaliq J Alsalman,Mohammed Al Mohaini,Kifayat Ullah Shah,Zahid Rasul Niazi,Arshad Farid,Kamran Ahmad Khan,Maitham A Al Hawaj,Yousef N Alhashem,Shakira Ghazanfar

doi:10.3390/gels8020129

Abstract

The currently available topical formulations of tacrolimus have minimal and variable absorption, elevated mean disposition half-life, and skin irritation effects resulting in patient noncompliance. In our study, we fabricated tacrolimus-loaded solid lipid nanoparticles (SLNs) that were converted into a gel for improved topical applications. The SLNs were prepared using a solvent evaporation method and characterized for their physicochemical properties. The particle size of the SLNs was in the range of 439 nm to 669 nm with a PDI of ≤0.4, indicating a monodispersed system. The Zeta potential of uncoated SLNs (F1–F5) ranged from −25.80 to −15.40 mV. Those values reverted to positive values for chitosan-decorated formulation (F6). The drug content and entrapment efficiency ranged between 0.86 ± 0.03 and 0.91 ± 0.03 mg/mL and 68.95 ± 0.03 and 83.68 ± 0.04%, respectively. The pH values of 5.45 to 5.53 depict their compatibility for skin application. The surface tension of the SLNs decreased with increasing surfactant concentration that could increase the adherence of the SLNs to the skin. The release of drug from gel formulations was significantly retarded in comparison to their corresponding SLN counterparts (p ≤ 0.05). Both SLNs and their corresponding gel achieved the same level of drug permeation, but the retention of the drug was significantly improved with the conversion of SLNs into their corresponding gel formulation (p ≤ 0.05) due to its higher bioadhesive properties.

Highlights

Topical administration is the route of choice for cutaneous pathologies like atopic dermatitis since it rarely presents systemic adverse effects when compared to other routes of drug administration [1]
The stratum corneum of the skin, composed of flat dead cells encompassing high keratin filaments surrounded by a lipophilic matrix consisting of keratin, ceramides, cholesterol, cholesterol esters, and various other fatty acids, provides a natural physical barrier against particle penetration [2,3]
Many transdermal methods have been tried to overcome the barrier function of the stratum corneum and achieve required transdermal permeability, but nanotechnology has developed an attractive niche in transdermal drug delivery

Summary

Introduction

Human skin provides the most comfortably accessible route of drug administration. The stratum corneum of the skin, composed of flat dead cells encompassing high keratin filaments surrounded by a lipophilic matrix consisting of keratin, ceramides, cholesterol, cholesterol esters, and various other fatty acids, provides a natural physical barrier against particle penetration [2,3]. Many transdermal methods have been tried to overcome the barrier function of the stratum corneum and achieve required transdermal permeability, but nanotechnology has developed an attractive niche in transdermal drug delivery. The physicochemical properties of nanoparticles such as size, shape, viscosity, and surface tension have a significant effect on dermal drug delivery [4], but the importance of nanoparticle composition cannot be underestimated [5]

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Conclusion