Dissolvable carboxymethyl cellulose/polyvinylpyrrolidone microneedle arrays for transdermal delivery of Amphotericin B to treat cutaneous leishmaniasis

Int J Biol Macromol. 2021 Jul 1:182:1310-1321. doi: 10.1016/j.ijbiomac.2021.05.075. Epub 2021 May 14.

Abstract

Cutaneous leishmaniasis (CL) is a significant public health problem caused by different species of Leishmania parasites. Due to low skin permeability, the development of an effective system for delivery of Amphotericin B (AMB), the common effective drug for leishmaniasis treatment, is required to replace the unpleasant and problematic injections. To overcome this problem, a dissolvable microneedle (MN) patch was developed, using biodegradable polymers (a mixture of polyvinylpyrrolidone and carboxymethyl cellulose) for AMB's transdermal delivery. Scanning electron microscopy and fluorescent images showed successful fabrication of the MNs and homogeneous dispersion of the drug into the needles. MNs showed good mechanical properties with the ability to penetrate the rat skin and reach the lower layers. After insertion to the skin, the MNs were rapidly dissolved to release the encapsulated drug, and the resulted micropores in the skin were quickly resealed within 30 min. MN patches showed non-toxicity as exposed to HT-29 cell line. Flow cytometry results showed a potent in vitro leishmanicidal activity of AMB-loaded MN patches against the Leishmania parasites (up to 86% of the parasites' death). Taken together, MN patches might represent a new, efficient and clinically translational approach for transdermal AMB delivery to treat CL.

Keywords: Amphotericin B; Carboxymethyl cellulose; Drug delivery; Leishmania; Microneedle patch; Polyvinylpyrrolidone.

MeSH terms

  • Administration, Cutaneous
  • Amphotericin B / administration & dosage*
  • Amphotericin B / pharmacology
  • Amphotericin B / therapeutic use*
  • Animals
  • Carboxymethylcellulose Sodium / chemistry*
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • HT29 Cells
  • Humans
  • Leishmaniasis, Cutaneous / drug therapy*
  • Male
  • Needles*
  • Optical Imaging
  • Povidone / chemistry*
  • Rats
  • Rats, Sprague-Dawley
  • Skin / drug effects
  • Spectroscopy, Fourier Transform Infrared
  • Transdermal Patch

Substances

  • Amphotericin B
  • Povidone
  • Carboxymethylcellulose Sodium