Oral delivery and enhanced efficacy of antimonal drug through macrophageguided multifunctional nanocargoes against visceral Leishmaniasis

Sarwar, Hafiz Shoaib and Sohail, Muhammad Farhan Oral delivery and enhanced efficacy of antimonal drug through macrophageguided multifunctional nanocargoes against visceral Leishmaniasis. European journal of pharmaceutics and biopharmaceutics.

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Abstract

The present study aimed on the site specific delivery and enhanced in-vivo efficacy of antimonial
drugs against the visceral leishmaniasis via macrophage targeted mannose anchored thiomer based
nanoparticles. Mannose anchored thiolated nanoformulation [M-(CS-g-PEI)-TGA] was developed
and evaluated in terms particle size, zeta-potential and entrapment efficacy. The TEM and EDX
analysis was carried out to evaluate the morphology and successful entrapment of antimonial drug.
Mucodhesion, permeation enhancement, oral pharmacokinetics, and in-vivo anti-leishmanial
activity were carried out. The M-(CS-g-PEI)-TGA were found to be spherical having particle size
of 287 ± 20 nm. Ex-vivo permeation indicated a 7.39-fold enhanced permeation of Meglumine
Antimoniate with M-(CS-g-PEI)-TGA across Caco-2 cells compared to the Glucantime.
Evaluation of in-vitro reduction in the parasitic burden via flow cytometric analysis indicated a
5.7-fold lower IC50 for M-(CS-g-PEI)-TGA compared to Glucantime. A 6.1-fold improvement in
the oral bioavailability and 5.2-fold reduced parasitic burden in the L. donovani infected BALB/c
mice model was observed with M-(CS-g-PEI)-TGA compared to Glucantime. The results
encouraged the concept of M-(CS-g-PEI)-TGA nanoformulations as a promising strategy for oral
therapy against visceral leishmaniasis.

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