Co-delivery of amphotericin B and pentamidine loaded niosomal gel for the treatment of Cutaneous leishmaniasis

Abstract

Topical drug delivery is preferable route over systemic delivery in case of Cutaneous leishmaniasis (CL). Among the available agents, amphotericin B (AmB) and pentamidine (PTM) showed promising result against CL. However, monotherapy is associated with incidences of reoccurrence and resistance. Combination therapy is therefore recommended. Thin film hydration method was employed for amphotericin B-pentamidine loaded niosomes (AmB-PTM-NIO) preparation followed by their incorporation into chitosan gel. The optimization of AmB-PTM-NIO was done via Box Behnken Design method and in vitro and ex vivo analysis was performed. The optimized formulation indicated 226 nm particle size (PS) with spherical morphology, 0.173 polydispersity index (PDI), −36 mV zeta potential (ZP) and with entrapment efficiency (EE) of 91% (AmB) and 79% (PTM), respectively. The amphotericin B-pentamidine loaded niosomal gel (AmB-PTM-NIO-Gel) showed desirable characteristics including physicochemical properties, pH (5.1 ± 0.15), viscosity (31870 ± 25 cP), and gel spreadability (280 ± 26.46%). In vitro release of the AmB and PTM from AmB-PTM-NIO and AmB-PTM-NIO-Gel showed more prolonged release behavior as compared to their respective drug solution. Higher skin penetration, greater percentage inhibition and lower IC50 against the promastigotes shows that AmB-PTM-NIO has better antileishmanial activity. The obtained findings suggested that the developed AmB-PTM-NIO-Gel has excellent capability of permeation via skin layers, sustained release profile and augmented anti-leishmanial outcome of the incorporated drugs.

Keywords:

• Cutaneous leishmaniasis
• niosomes
• amphotericin B
• pentamidine
• AmB-PTM-NIO-Gel
• topical delivery

Acknowledgments

Authors are thankful to Higher Education Commission (HEC) of Pakistan for their financial support. Moreover, the authors are grateful to the Deanship of Scientific Research at King Khalid University for funding this study through the Research Group Project, under grant number RGP. 1/326/43.

Institutional review board statement

The animal study protocol was approved by the Institutional Review Board (or Ethics Committee) of Quaid-i-Azam University, Islamabad under the approval no BEC-FBS-QAU2021-320.

Disclosure statement

The authors declare no conflict of interest.

Data availability statement

Data will be made available on request.

Author contribution

Adnan Anjum, kanwal shabbir and shumaila shafique: Data curation, Formal analysis, Investigation, Writing - original draft. Syed Saoud Zaidi, Ali H Almari, Taha Alqahtani: Investigation, Software, Writing - review & editing. Aleena Maryam, Muhammad Moneeb, Adel Al Fatease and Sidra Bashir: Methodology, v alidation, Visualization. Fakhar ud Din and Gul Majid Khan: Conceptualization, Administration, Funding.

Additional information

Funding

This research work was funded by Higher Education Commission (HEC) of Pakistan through its grant No: 6171/Federal/NRPU R&D/HEC/2016 and HEC/NRPU/R&D/No: 14604/2021.