Development and evaluation of novel miltefosine-polyphenol co-loaded second generation nano-transfersomes for the topical treatment of cutaneous leishmaniasis. (2nd January 2020)

• Record Type: Journal Article
• Authors: Dar, M. Junaid; McElroy, Craig A.; Khan, Muhammad Ijaz; Satoskar, Abhay R.; Khan, Gul Majid
• Is Part Of: Expert opinion on drug delivery. Volume 17:Number 1(2020)
• Page Start: 97
• Page End: 110
• Publication Date: 2020-01-02
• Subjects: Miltefosine -- apigenin -- co-loaded second generation nano-transfersomes -- topical therapy -- macrophage targeting -- cutaneous leishmaniasis; Drug delivery devices -- Periodicals; Drug delivery systems -- Periodicals; 615.605
• DOI: 10.1080/17425247.2020.1700227
• Languages: English
• ISSNs: 1742-5247

Abstract

ABSTRACT: Objective : To test the hypothesis that miltefosine (MTF)-polyphenol co-loaded second-generation nano-transfersomes (SGNTs) can be an effective approach for the topical treatment of cutaneous leishmaniasis (CL). Methods : The co-loaded SGNTs with various MTF-polyphenol combinations were developed, evaluated and compared for the entrapment efficiency, vesicle size, deformability index, ex-vivo permeation, cytotoxicity, and anti-leishmanial potential, using both in-vitro and in-vivo models. Results : The co-loaded SGNTs were spherical in shape, with an average size of 119 ± 1.5 nm and a high entrapment efficiency of 73.7 ± 3.7%. The ex-vivo study displayed a 3.2-fold higher permeation of MTF when entrapped in co-loaded SGNTs, whereas cytotoxicity potential of co-loaded SGNTs was 43.2% higher than the MTF solution. A synergistic interaction was observed between MTF and apigenin (APG) among all polyphenols and an 8.0-fold lower IC50 was found against amastigotes of DsRed Leishmania mexicana, compared with the plain MTF solution. Moreover, the in-vivo studies displayed a 9.5-fold reduced parasitic burden in the L. mexicana infected BALB/c mice treated with MTF-APG co-loaded SGNTs gel. Conclusions : The potential of MTF-APG co-loaded SGNTs topical formulation is established for the first time as an effective drug delivery strategy against CL.