Co-delivery of amphotericin B and pentamidine loaded niosomal gel for the treatment of Cutaneous leishmaniasis .
Adnan AnjumKanwal ShabbirFakhar Ud DinShumaila ShafiqueSyed Saoud ZaidiAli H AlmariTaha AlqahtaniAleena MaryiamMuhammad Moneeb KhanAdel Al FateaseSidra BashirGul Majid KhanPublished in: Drug delivery (2023)
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.
Keyphrases
- wound healing
- drug delivery
- combination therapy
- hyaluronic acid
- cancer therapy
- randomized controlled trial
- drug release
- emergency department
- transcription factor
- open label
- soft tissue
- risk assessment
- binding protein
- study protocol
- smoking cessation
- molecularly imprinted
- replacement therapy
- solar cells
- solid phase extraction