Iqra Afzal1, Hafiz Shoaib Sarwar1,2, Muhammad Farhan Sohail1,2, Sanjay Varikuti3, Sarwat Jahan4, Sohail Akhtar5, Masoom Yasinzai6, Abhay R Satoskar3, Gul Shahnaz1,3. 1. Department of Pharmacy, Quaid-I-Azam University, Islamabad 44000, Pakistan. 2. Riphah Institute of Pharmaceutical Science, Riphah International University, Lahore Campus, Lahore, Pakistan. 3. Department of Pathology, Ohio State University Medical Center, Columbus, OH 43201, USA. 4. Department of Animal Sciences, Quaid-I-Azam University, Islamabad 44000, Pakistan. 5. Department of Entomology, University College of Agriculture & Environmental Sciences, The Islamia University, Bahawalpur, Pakistan. 6. Centre for Interdisciplinary Research in Basic Sciences, International Islamic University, Islamabad, Pakistan.
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.
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.
Authors: Kercia P Cruz; Beatriz F C Patricio; Vinícius C Pires; Marina F Amorim; Alan G S F Pinho; Helenita C Quadros; Diana A S Dantas; Marcelo H C Chaves; Fabio R Formiga; Helvécio V A Rocha; Patrícia S T Veras Journal: Front Chem Date: 2021-05-13 Impact factor: 5.221