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| Content Provider | Springer Nature Link |
|---|---|
| Author | Asthana, Shalini Gupta, Pramod K. Jaiswal, Anil K. Dube, Anuradha Chourasia, Manish K. |
| Copyright Year | 2015 |
| Abstract | Since, Leishmania protozoans are obligate intracellular parasites of macrophages, an immunopotentiating macrophage-specific Amphotericin B (AB) delivery system would be ideally appropriate to increase its superiority for leishmaniasis treatment and to eliminate undesirable toxicity. Herein, we report AB entrapped mannose grafted chitosan nanocapsules (MnosCNc-AB) that results in effective treatment of visceral leishmaniasis, while also enhancing L. donovani specific T-cell immune responses in infected host. MnosCNc-AB were prepared via synthesized mannosylated chitosan deposition on interface of oil/water nanoemulsion intermediate and were characterized. J774A.1 macrophage uptake potential, antileishmanial activity and immunomodulatory profile were evaluated in hamster. Tissue localization, biodistribution and toxicity profile were also investigated. MnosCNc-AB had nanometric size (197.8 ± 8.84 nm), unimodal distribution (0.115 ± 0.04), positive zeta potential (+31.7 ± 1.03 mV) and 97.5 ± 1.13% cargo encapsulation efficiency. Superior macrophage internalization of mannosylated chitosan nanocapsules compared to unmodified chitosan nanocapsules was observed by fluorescence-based assessment, further confirmed by rapid blood clearance and, greater localization and higher accumulation in macrophage rich liver and spleen. While, MnosCNc-AB mediated cargo distribution to kidney decreased. Augmented in vitro antileishmanial activity and in vivo pro-inflammatory mediator’s expression were observed with MnosCNc-AB, led to significant reduction (∼90%) in splenic parasite burden.Results demonstrated that mannose ligand grafted chitosan nanocapsules could improve selective delivery of AB into macrophages via interactions with overexpressed mannose receptors thus reduce undesirable toxicity. Study provides evidence for MnosCNc-AB potential to leishmaniasis therapeutics and presents valuable therapeutic strategies for combating chronic macrophage-resident microbial infections. |
| Starting Page | 2663 |
| Ending Page | 2677 |
| Page Count | 15 |
| File Format | |
| ISSN | 07248741 |
| Journal | Pharmaceutical Research |
| Volume Number | 32 |
| Issue Number | 8 |
| e-ISSN | 1573904X |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2015-02-27 |
| Publisher Place | New York |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering |
| Content Type | Text |
| Resource Type | Article |
| Subject | Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science |
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