Mannosylated thiolated paromomycin-loaded PLGA nanoparticles for the oral therapy of visceral leishmaniasis. (28th January 2019)

• Record Type: Journal Article
• Authors: Afzal, Iqra; Sarwar, Hafiz Shoaib; Sohail, Muhammad Farhan; Varikuti, Sanjay; Jahan, Sarwat; Akhtar, Sohail; Yasinzai, Masoom; Satoskar, Abhay R; Shahnaz, Gul
• Is Part Of: Nanomedicine. Volume 14:Number 4(2019)
• Page Start: 387
• Page End: 406
• Publication Date: 2019-01-28
• Subjects: L. donovani -- macrophage targeting -- mannose receptors -- oral therapy -- paromomycin -- thiolated chitosan -- visceral leishmaniasis; Nanotechnology -- Periodicals; Medical technology -- Periodicals; Nanotechnology -- Therapeutic use -- Periodicals; 610.28
• DOI: 10.2217/nnm-2018-0038
• Languages: English
• ISSNs: 1743-5889

Abstract

Aim: The present study evaluates the efficacy of paromomycin (PM)-loaded mannosylated thiomeric nanoparticles for the targeted delivery to pathological organs for the oral therapy of visceral leishmaniasis.Materials & methods: Mannosylated thiolated chitosan (MTC)-coated PM-loaded PLGA nanoparticles (MTC-PLGA-PM) were synthesized and evaluated for morphology, drug release, permeation enhancing and antileishmanial potential.Results: MTC-PLGA-PM were spherical in shape with a size of 391.24 ± 6.91 nm and an encapsulation efficiency of 67.16 ± 14%. Ex vivo permeation indicated 12.73-fold higher permeation of PM with MTC-PLGA-PM against the free PM. Flow cytometry indicated enhanced macrophage uptake and parasite killing in Leishmania donovani infected macrophage model. In vitro antileishmanial activity indicated 36-fold lower IC50 for MTC-PLGA-PM as compared with PM. The in vivo studies indicated 3.6-fold reduced parasitic burden in the L. donovani infected BALB/c mice model.Conclusion: The results encouraged the concept of MTC-PLGA-PM nanoparticles as promising strategy for visceral leishmaniasis.