Development and evaluation of novel miltefosine-polyphenol co-loaded second generation nano-transfersomes for the topical treatment of cutaneous leishmaniasis.
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.
['Dar|M Junaid|MJ|0000-0003-0210-4412', 'McElroy|Craig A|CA|', 'Khan|Muhammad Ijaz|MI|', 'Satoskar|Abhay R|AR|', 'Khan|Gul Majid|GM|0000-0003-3282-1711']
D000287:Administration, Topical D000818:Animals D000981:Antiprotozoal Agents D002851:Chromatography, High Pressure Liquid D002853:Chromatography, Liquid D004337:Drug Carriers D016503:Drug Delivery Systems D005260:Female D007894:Leishmania mexicana D016773:Leishmaniasis, Cutaneous D008081:Liposomes D008264:Macrophages D051379:Mice D008807:Mice, Inbred BALB C D053758:Nanoparticles D021261:Parasitic Sensitivity Tests D010713:Phosphatidylcholines D010767:Phosphorylcholine D059808:Polyphenols D053719:Tandem Mass Spectrometry
co-loaded second generation nano-transfersomes cutaneous leishmaniasis Miltefosine apigenin macrophage targeting topical therapy