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Pharmaceutical Research

, 35:60 | Cite as

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

  • Pankaj K. Singh
  • Anil K. Jaiswal
  • Vivek K. Pawar
  • Kavit Raval
  • Animesh Kumar
  • Himangsu K. Bora
  • Anuradha Dube
  • Manish K. Chourasia
Research Paper
  • 185 Downloads

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.

KEY WORDS

3-O-sn-Phosphatidyl-L-serine amphotericin B macrophage targeting visceral leishmaniasis 

ABBREVIATIONS

AmpB

Amphotericin B

AmpT

Amphotreat

LamN

Lambin

PhoS

3-O-sn-Phosphatidyl-L-serine

PLGA

Poly (lactic-co-glycolic acid)

VL

Visceral leishmaniasis

Notes

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.

References

  1. 1.
    Asthana S, Jaiswal AK, Gupta PK, Dube A, Chourasia MK. Th-1 biased immunomodulation and synergistic antileishmanial activity of stable cationic lipid–polymer hybrid nanoparticle: biodistribution and toxicity assessment of encapsulated amphotericin B. Eur J Pharm Biopharm. 2015;89:62–73.CrossRefPubMedGoogle Scholar
  2. 2.
    Sundar S, More DK, Singh MK, Singh VP, Sharma S, Makharia A, et al. Failure of pentavalent antimony in visceral leishmaniasis in India: report from the center of the Indian epidemic. Clin Infect Dis. 2000;31:1104–7.CrossRefPubMedGoogle Scholar
  3. 3.
    Tiuman TS, Santos AO, Ueda-Nakamura T, Filho BP, Nakamura CV. Recent advances in leishmaniasis treatment. Int J Infect Dis. 2011;15:e525–32.CrossRefPubMedGoogle Scholar
  4. 4.
    Boelaert M, Criel B, Leeuwenburg J, Van Damme W, Le Ray D, Van der Stuyft P. Visceral leishmaniasis control: a public health perspective. Trans R Soc Trop Med Hyg. 2000;94:465–71.CrossRefPubMedGoogle Scholar
  5. 5.
    Krieger M. Scavenger receptor class B type I is a multiligand HDL receptor that influences diverse physiologic systems. J Clin Invest. 2001;108:793–7.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Ravichandranand KS, Lorenz U. Engulfment of apoptotic cells: signals for a good meal. Nat Rev Immunol. 2007;7:964–74.CrossRefGoogle Scholar
  7. 7.
    Platt N, da Silva RP, Gordon S. Class A scavenger receptors and the phagocytosis of apoptotic cells. Immunol Lett. 1999;65:15–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Schlegeland RA, Williamson P. Phosphatidylserine, a death knell. Cell Death Differ. 2001;8:551–63.CrossRefGoogle Scholar
  9. 9.
    Kansal S, Tandon R, Dwivedi P, Misra P, Verma PR, Dube A, et al. Development of nanocapsules bearing doxorubicin for macrophage targeting through the phosphatidylserine ligand: a system for intervention in visceral leishmaniasis. J Antimicrob Chemother. 2012;67:2650–60.CrossRefPubMedGoogle Scholar
  10. 10.
    Chen X, Doffek K, Sugg SL, Shilyansky J. Phosphatidylserine regulates the maturation of human dendritic cells. J Immunol (Baltimore, Md : 1950). 2004;173:2985–94.CrossRefGoogle Scholar
  11. 11.
    Khatik R, Dwivedi P, Khare P, Kansal S, Dube A, Mishra PR, et al. Development of targeted 1,2-diacyl-sn-glycero-3-phospho-l-serine-coated gelatin nanoparticles loaded with amphotericin B for improved in vitro and in vivo effect in leishmaniasis. Expert Opin Drug Deliv. 2014;11:633–46.CrossRefPubMedGoogle Scholar
  12. 12.
    Geelen T, Yeo SY, Paulis LE, Starmans LW, Nicolay K, Strijkers GJ. Internalization of paramagnetic phosphatidylserine-containing liposomes by macrophages. J Nanobiotechnol. 2012;10:37.CrossRefGoogle Scholar
  13. 13.
    Tempone AG, Perez D, Rath S, Vilarinho AL, Mortara RA, de Andrade HF Jr. Targeting Leishmania (L.) chagasi amastigotes through macrophage scavenger receptors: the use of drugs entrapped in liposomes containing phosphatidylserine. J Antimicrob Chemother. 2004;54:60–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Danhier F, Ansorena E, Silva JM, Coco R, Le Breton A, Préat V. PLGA-based nanoparticles: An overview of biomedical applications. J Control Release. 2012;161:505–22.CrossRefPubMedGoogle Scholar
  15. 15.
    Bala I, Hariharan S, Kumar MN. PLGA nanoparticles in drug delivery: the state of the art. Crit Rev Ther Drug Carrier Syst. 2004;21:387–422.CrossRefPubMedGoogle Scholar
  16. 16.
    Singh PK, Sah P, Meher JG, Joshi S, Pawar VK, Raval K, et al. Macrophage-targeted chitosan anchored PLGA nanoparticles bearing doxorubicin and amphotericin B against visceral leishmaniasis. RSC Adv. 2016;6:71705–18.CrossRefGoogle Scholar
  17. 17.
    Singh P, Gupta A, Jaiswal A, Dube A, Mishra S, Chaurasia MK. Design and development of Amphotericin B bearing polycaprolactone microparticles for macrophage targeting. J Biomed Nanotechnol. 2011;7:50–1.CrossRefPubMedGoogle Scholar
  18. 18.
    Guzzarlamudi S, Singh PK, Pawar VK, Singh Y, Sharma K, Paliwal SK, et al. Synergistic Chemotherapeutic Activity of Curcumin Bearing Methoxypolyethylene Glycol-g-Linoleic Acid Based Micelles on Breast Cancer Cells. J Nanosci Nanotechnol. 2016;16:4180–90.CrossRefPubMedGoogle Scholar
  19. 19.
    Chaurasia M, Singh PK, Jaiswal AK, Kumar A, Pawar VK, Dube A, et al. Bioinspired Calcium Phosphate Nanoparticles Featuring as Efficient Carrier and Prompter for Macrophage Intervention in Experimental Leishmaniasis. Pharm Res. 2016;33:2617–29.CrossRefPubMedGoogle Scholar
  20. 20.
    Pawar VK, Panchal SB, Singh Y, Meher JG, Sharma K, Singh P, et al. Immunotherapeutic vitamin E nanoemulsion synergies the antiproliferative activity of paclitaxel in breast cancer cells via modulating Th1 and Th2 immune response. J Control Release. 2014;196:295–306.CrossRefPubMedGoogle Scholar
  21. 21.
    Gupta PK, Jaiswal AK, Asthana S, Verma A, Kumar V, Shukla P, et al. Self Assembled Ionically Sodium Alginate Cross-Linked Amphotericin B Encapsulated Glycol Chitosan Stearate Nanoparticles: Applicability in Better Chemotherapy and Non-Toxic Delivery in Visceral Leishmaniasis. Pharm Res. 2015;32:1727–40.CrossRefPubMedGoogle Scholar
  22. 22.
    Gupta G, Oghumu S, Satoskar AR. Mechanisms of Immune Evasion in Leishmaniasis. Adv Appl Microbiol. 2013;82:155–84.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Asthana S, Jaiswal AK, Gupta PK, Pawar VK, Dube A, Chourasia MK. Immunoadjuvant chemotherapy of visceral leishmaniasis in hamsters using Amphotericin B-encapsulated nanoemulsion template-based chitosan nanocapsules. Antimicrob Agents Chemother. 2013;57:1714–22.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Sundar S, Mehta H, Suresh AV, Singh SP, Rai M, Murray HW. Amphotericin B treatment for Indian visceral leishmaniasis: conventional versus lipid formulations. Clin Infect Dis: Off Publ Infect Dis Soc Am. 2004;38:377–83.CrossRefGoogle Scholar
  25. 25.
    Ravichandran KS. Find-me and eat-me signals in apoptotic cell clearance: progress and conundrums. J Exp Med. 2010;207:1807–17.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Makadiaand HK, Siegel SJ. Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier. Polymers. 2011;3:1377–97.CrossRefGoogle Scholar
  27. 27.
    Omar Zaki SS, Ibrahim MN, Katas H. Particle size affects concentration-dependent cytotoxicity of chitosan nanoparticles towards mouse hematopoietic stem cells. J Nanotechnol. 2015;2015:1–5.CrossRefGoogle Scholar
  28. 28.
    He C, Hu Y, Yin L, Tang C, Yin C. Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles. Biomaterials. 2010;31:3657–66.CrossRefPubMedGoogle Scholar
  29. 29.
    Knopik-Skrockaand A, Bielawski J. Differences in amphotericin-B-induced hemolysis between human erythrocytes from male and female donors. Biol Lett. 2005;42:49–60.Google Scholar
  30. 30.
    Kotler-Brajtburg J, Medoff G, Kobayashi G, Boggs S, Schlessinger D, Pandey R, et al. Classification of polyene antibiotics according to chemical structure and biological effects. Antimicrob Agents Chemother. 1979;15:716–22.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Wu Y, Tibrewal N, Birge RB. Phosphatidylserine recognition by phagocytes: a view to a kill. Trends Cell Biol. 2006;16:189–97.CrossRefPubMedGoogle Scholar
  32. 32.
    Kimani SG, Geng K, Kasikara C, Kumar S, Sriram G, Wu Y, et al. Contribution of Defective PS Recognition and Efferocytosis to Chronic Inflammation and Autoimmunity. Front Immunol. 2014;5:566.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Galvan MD, Foreman DB, Zeng E, Tan JC, Bohlson SS. Complement component C1q regulates macrophage expression of Mer tyrosine kinase to promote clearance of apoptotic cells. J Immunol (Baltimore, Md : 1950). 2012;188:3716–23.CrossRefGoogle Scholar
  34. 34.
    Osterand CN, Nacy CA. Macrophage activation to kill Leishmania tropica: kinetics of macrophage response to lymphokines that induce antimicrobial activities against amastigotes. J Immunol. 1984;132:1494–500.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Pankaj K. Singh
    • 1
  • Anil K. Jaiswal
    • 2
  • Vivek K. Pawar
    • 1
  • Kavit Raval
    • 1
  • Animesh Kumar
    • 1
  • Himangsu K. Bora
    • 3
  • Anuradha Dube
    • 2
  • Manish K. Chourasia
    • 1
  1. 1.Pharmaceutics and Pharmacokinetics DivisionCSIR-Central Drug Research InstituteLucknowIndia
  2. 2.Parasitology DivisionCSIR-Central Drug Research InstituteLucknowIndia
  3. 3.Laboratory Animal FacilityCSIR-Central Drug Research InstituteLucknowIndia

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