Chitosan-Coated 5-Fluorouracil Incorporated Emulsions as Transdermal Drug Delivery Matrices.

Taif Ali Khan,Neeraj Kumar Fuloria,Muhammad Akhlaq,Abul Kalam Azad,Omji Porwal,Asif Nawaz,Mahendran Sekar,Vetriselvan Subramaniyan,Rishabha Malviya,Shivkanya Fuloria,Muhammad Safdar,Mireia Mallandrich Miret,Ajay Mendiratta,Dhanalekshmi Unnikrishnan Meenakshi,Kathiresan V Sathasivam

doi:10.3390/polym13193345

Abstract

The purpose of the present study was to develop emulsions encapsulated by chitosan on the outer surface of a nano droplet containing 5-fluorouracil (5-FU) as a model drug. The emulsions were characterized in terms of size, pH and viscosity and were evaluated for their physicochemical properties such as drug release and skin permeation in vitro. The emulsions containing tween 80 (T80), sodium lauryl sulfate, span 20, and a combination of polyethylene glycol (PEG) and T20 exhibited a release of 88%, 86%, 90% and 92%, respectively. Chitosan-modified emulsions considerably controlled the release of 5-FU compared to a 5-FU solution (p < 0.05). All the formulations enabled transportation of 5-FU through a rat’s skin. The combination (T80, PEG) formulation showed a good penetration profile. Different surfactants showed variable degrees of skin drug retention. The ATR-FTIR spectrograms revealed that the emulsions mainly affected the fluidization of lipids and proteins of the stratum corneum (SC) that lead to enhanced drug permeation and retention across the skin. The present study concludes that the emulsions containing a combination of surfactants (Tween) and a co-surfactant (PEG) exhibited the best penetration profile, prevented the premature release of drugs from the nano droplet, enhanced the permeation and the retention of the drug across the skin and had great potential for transdermal drug delivery. Therefore, chitosan-coated 5-FU emulsions represent an excellent possibility to deliver a model drug as a transdermal delivery system.

Highlights

The transdermal drug delivery system (TDDS) offers several advantages over the other conventional drug delivery systems [1]
The prepared emulsions exhibited zeta-potential ranging from +3.7 ± 0.61 mV to +5.5 ± 0.52 mV, attributed to the presence of chitosan, as shown in Figure 1b and Table 1
The use of a mixed system of surfactants and co-surfactants resulted in a higher positive zeta-potential by keeping chitosan at the surface of the nanodroplets

Summary

Introduction

The transdermal drug delivery system (TDDS) offers several advantages over the other conventional drug delivery systems [1]. The TDDS is known to avoid the first-pass metabolism, offer stable drug delivery, exhibit a decreased systemic drug interaction, improve patient compliance, reduce the frequency of drug administration, and offer higher therapeutic efficacy and safety [2,3]. Permeation enhancers are associated with various problems, for example, an increase in the concentration of DMSO can trigger erythema or SC swelling. It can cause the denaturing of skin proteins that may lead to scaling, stinging, erythema, irreversible membrane damage, urticaria contact, and a burning sensation as well [10,11]

Objectives

Results

Conclusion