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Fabrication of 3-O-sn-Phosphatidyl-L-serine Anchored PLGA Nanoparticle Bearing Amphotericin B for Macrophage Targeting

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ABSTRACT

Purpose

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.

Results

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.

Conclusion

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.

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Abbreviations

AmpB:

Amphotericin B

AmpT:

Amphotreat

LamN:

Lambin

PhoS:

3-O-sn-Phosphatidyl-L-serine

PLGA:

Poly (lactic-co-glycolic acid)

VL:

Visceral leishmaniasis

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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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Authors and Affiliations

  1. Pharmaceutics and Pharmacokinetics Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, UP, 226031, India

    Pankaj K. Singh, Vivek K. Pawar, Kavit Raval, Animesh Kumar & Manish K. Chourasia

  2. Parasitology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, UP, 226031, India

    Anil K. Jaiswal & Anuradha Dube

  3. Laboratory Animal Facility, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, UP, 226031, India

    Himangsu K. Bora

Authors
  1. Pankaj K. Singh
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  2. Anil K. Jaiswal
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  3. Vivek K. Pawar
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  7. Anuradha Dube
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  8. Manish K. Chourasia
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Correspondence to Manish K. Chourasia.

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Singh, P.K., Jaiswal, A.K., Pawar, V.K. et al. Fabrication of 3-O-sn-Phosphatidyl-L-serine Anchored PLGA Nanoparticle Bearing Amphotericin B for Macrophage Targeting. Pharm Res 35, 60 (2018). https://doi.org/10.1007/s11095-017-2293-1

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