Fabrication of 3-O-sn-Phosphatidyl-L-serine Anchored PLGA Nanoparticle Bearing Amphotericin B for Macrophage Targeting
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To fabricate, characterize and evaluate 3-O-sn-Phosphatidyl-L-serine (PhoS) anchored PLGA nanoparticles for macrophage targeted therapeutic intervention of VL.
Materials and Methods
PLGA-AmpB NPs were prepared by well-established nanoprecipitation method and decorated with Phos by thin film hydration method. Physico-chemical characterization of the formulation was done by Zetasizer nano ZS and atomic force microscopy.
The optimized formulation (particle size, 157.3 ± 4.64 nm; zeta potential, − 42.51 ± 2.11 mV; encapsulation efficiency, ∼98%) showed initial rapid release up to 8 h followed by sustained release until 72 h. PhoS generated ‘eat-me’ signal driven augmented macrophage uptake, significant increase in in-vitro (with ∼82% parasite inhibition) and in-vivo antileishmanial activity with preferential accumulation in macrophage rich organs liver and spleen were found. Excellent hemo-compatibility justified safety profile of developed formulation in comparison to commercial formulations.
The developed PhoS-PLGA-AmpB NPs have improved efficacy, and necessary stability which promisingly put itself as a better alternative to available commercial formulations for optimized treatment of VL.
KEY WORDS3-O-sn-Phosphatidyl-L-serine amphotericin B macrophage targeting visceral leishmaniasis
Poly (lactic-co-glycolic acid)
ACKNOWLEDGMENTS AND DISCLOSURES
We wish to acknowledge the financial support extended by Department of Science and Technology, Government of India under the project SR/SO/HS-218/2012. The authors are grateful to SAIF, CDRI, Lucknow for providing the flow cytometry facility. All authors declare no conflict of interest. This is CSIR-CDRI communication 9583.
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