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Drug Delivery and Translational Research

, Volume 5, Issue 5, pp 489–497 | Cite as

Development and evaluation of anti-malarial bio-conjugates: artesunate-loaded nanoerythrosomes

  • Jaya AgnihotriEmail author
  • Shubhini Saraf
  • Sobhna Singh
  • Papiya Bigoniya
Original Article

Abstract

Biodegradable cellular carrier has desired properties for achieving effective long-term controlled release of drugs having short half life. To reduce the undesired effects of drug, advanced drug delivery systems are needed which are based on specific cell targeting module. Artesunate (ART) conjugation on nanoerythrosomes (NE) can have controlled delivery to avoid drug leakage, increase the stability, and reduce cost and toxicities. In this study nanosized lipoprotein membrane vesicles bearing ART were prepared by extrusion method. Developed ART-NE conjugate formulations were optimized on the basis of vesicle morphology, size and size distribution, polydispersity index, integrity of membrane, loaded drug concentration, drug leakage, effect of temperature and viscosity, syringeability, in vitro release profile and in vivo plasma concentration estimation studies. Fourier transform infrared (FTIR) spectroscopy reveals that lipid chain order of RBCs are insignificantly affected in moderate conditions after ART loading. The formulated ART-NE carrier revealed non aggregated, uniformly sized particles with smooth surfaces. The maximum drug loading was found to be 25.20 ± 1.3 μg/ml. ART-NE formulation was best fit for zero order kinetics and was found to be capable of controlled release of drug for 8 hrs. ART-NE formulation showed good redispersibility with desirable properties for parenteral administration. Formulation was stable when subjected to stress by centrifugal force of 7500 rpm and could bear turbulence shock of 15 passes from hypodermic needle of size 23 gauges. The ART-NE formulation administered intravenously showed higher plasma concentration compared to free drug signifying not only controlled release but higher rate of in vivo release. The developed formulation exhibited zero order release profile as per kinetic study analysis suggesting the suitability of carrier for the sustained and targeted delivery of ART. The developed ART-NE drug delivery system offers improved pharmacokinetic profile with assurance of increased therapeutic efficacy.

Keywords

Anti-malarial Artesunate Cellular carrier Erythrocytes Nanoerythrocytes Targeting 

Notes

Acknowledgments

The authors are thankful to Prof. Vandana B Patrawala, Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, and lab staff for their invaluable help in handling and operating of the instruments in their laboratory for this research work.

Conflict of interest

The authors declare that there is no conflict of interest.

References

  1. 1.
    Anvikar AR, Arora U, Sonal GS, Mishra N, Shahi B, Savargaonkar D, et al. Anti malarial drug policy in India: Past, present and future. Ind J Med Res. 2014;139(2):205–15.Google Scholar
  2. 2.
    Xiao XC, Hon Z. Firstborn microcrystallization method to prepare nanocapsules containing Artesunate. Int J Nanomedicine. 2010;5:483–6.PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    White NJ. Assessment of the pharmacodynamic properties of antimalarial drugs in vivo. Antimicrob Agents Chemother. 1997;41:1413–22.PubMedCentralPubMedGoogle Scholar
  4. 4.
    Wernsdorfer WH, Payne D. The dynamics of drug resistance in Plasmodium falciparum. Pharmacol Ther. 1991;50(1):95–121.CrossRefPubMedGoogle Scholar
  5. 5.
    White NJ. Artemisinin: current status. Trans R Soc Trop Med Hyg. 1994;88:S3–4.CrossRefPubMedGoogle Scholar
  6. 6.
    Meng H, Xu K, Xu Y, Luo P, Du F, Huang J, et al. Nanocapsules based on mPEGylated artesunate prodrug and its cytotoxicity. Colloid Surf B. 2014;115:164–9.CrossRefGoogle Scholar
  7. 7.
    Agnihotri J, Singh S, Bigonia P. Formal chemical stability analysis and solubility analysis of artesunate and hydroxychloroquinine for development of parenteral dosage form. J Pharm Res. 2013;6(1):117–22.CrossRefGoogle Scholar
  8. 8.
    Chadha R, Gupta S, Pathak N. Artesunate-loaded chitosan/lecithin nanoparticles: preparation, characterization, and in vivo studies. Drug Dev Ind Pharm. 2012;38(12):1538–46.CrossRefPubMedGoogle Scholar
  9. 9.
    Nguyen DT, Tran TH, Kim JO, Yong CS, Nguyen CN. Enhancing the in vitro anti-cancer efficacy of artesunate by loading into polyd, l-lactide-co-glycolide (PLGA) nanoparticles. Arch Pharm Res. 2015;38(5):716–24.CrossRefPubMedGoogle Scholar
  10. 10.
    Batty KT, Ilett KF, Davis ME. Chemical stability of artesunate injection and proposal for its administration by intravenous infusion. J Pharm Pharmacol. 1996;48(1):22–6.CrossRefPubMedGoogle Scholar
  11. 11.
    Tiwari G, Tiwari R, Srivastava B, Bhati L, Pandey P, Bannerjee S. Drug delivery systems: An updated review. Int J Pharm Investig. 2012;2(1):2–11.PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Muzykantov VR, Smirnov MD, Klibanov AL. Avidin attachment to biotinylated amino groups of the erythrocyte membrane eliminates homologous restriction of both classical and alternative pathways of the complement. FEBS Lett. 1993;318(2):108–12.CrossRefPubMedGoogle Scholar
  13. 13.
    Muzykantov VR, Seregina N, Smirnov MD. Fast lysis by complement and uptake by liver of avidin-carrying biotinylated erythrocytes. Int J Artif Organs. 1992;15:622–7.PubMedGoogle Scholar
  14. 14.
    Shi J, Kundrat L, Pishesha N, Bilate A, Theile C, Maruvama T, et al. Engineered red blood cells as carriers for systemic delivery of a wide array of functional probes. Proc Natl Acad Sci U S A. 2014;111(28):10131–6.PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Lejeune A, Moorjani M, Gicquaud C, Lacroix J, Povet P, Gaudreault R. Nanoerythrosomes, a new derivative of erythrocyte ghost: preparation and antineoplastic potential as drug carrier for daunorubicin. Anticancer Res. 1994;14(3A):915–9.PubMedGoogle Scholar
  16. 16.
    Gaudreault RC, Gicquaud C, Poyet P. Nanoerythrosome as bioactive agent carrier. 1997;US patent 5653999Google Scholar
  17. 17.
    Lanao JM, Sayalero ML. Cells and Cell Ghosts as Drug Carriers. In: Torchilin VP, editor. Nanoparticulates as Drug Carriers. London: World Scientific, Imperial College Press; 2006. p. 329–48.CrossRefGoogle Scholar
  18. 18.
    Jain S, Jain NK. Engineered erythrocytes as a drug delivery system. Ind J Pharm Sci. 1997;59(6):275–81.Google Scholar
  19. 19.
    Lejeune A, Moorjani M, Gicquaud C, Lacroix J, Povet P, Gaudreault R. Nanoerythrosomes, a new derivative of erythrocyte ghost II:Identification of the mechanism of action. Anticancer Res. 1996;16(5A):2831–6.PubMedGoogle Scholar
  20. 20.
    DeLoach RE, Droleskey K, Andrews K. Encapsulation by hypotonic dialysis in human erythrocytes: a diffusion or endocytosis process. Biotechnol Appl Biochem. 1991;13(1):72–82.PubMedGoogle Scholar
  21. 21.
    Agnihotri J, Jain NK, Gajbhiye V. Engineered cellular carrier nanoerythrosomes as potential targeting vectors for anti-malarial drug. Asian J Pharmaceutics. 2010;4(2):116–20.CrossRefGoogle Scholar
  22. 22.
    Bellemare F, Gaudreault R. Polyethyleneglycol conjugated nanoerythrosomes, method of making same and use thereof. 1998;Patent WO1998011919 A2.Google Scholar
  23. 23.
    Agnihotri J, Jain NK. Biodegradable long circulating cellular carrier for antimalarial drug pyrimethamine, Artificial Cells, Nanomedicine, and Biotechnology. 2013;41(5):309–14.Google Scholar
  24. 24.
    Gabriels M, Plaizier-Vercammen J. Physical and chemical evaluation of liposomes containing artesunate. J Pharm Biomed Anal. 2003;31(4):655–67.CrossRefPubMedGoogle Scholar
  25. 25.
    Seguro AC, Campos SB. Diuretic effect of sodium artesunate in patients with malaria. Am J Trop Med Hyg. 2002;67:473–4.PubMedGoogle Scholar
  26. 26.
    Merkus HG. Particle Size, Size Distribution and Shape. In: Particle Size Measurements: Fundamentals, Practice, Quality. Netherlands: Springer; 2009. p. 13 − 42Google Scholar
  27. 27.
    Particle size, Particle size distributions from sub-nanometer to millimetres. www.malvern.com. Available at: http://www.malvern.com/en/products/measurement-type/particle-size/default.aspx. Accessed on: 12th Dec. 2014.
  28. 28.
    Patravale V, Dandekar P, Jain R. Nanoparticulate Drug Delivery: Perspectives on the Transition from Laboratory to Market. In: Nanoparticulate Drug Delivery. 1st edition. UK: Woodhead Publishing Ltd; 2012. p. 65–7.Google Scholar
  29. 29.
    Liberman HA, Martin MR, Banker GS. Pharmaceutical Dosage forms Dispersed systems. Vol 2. New York: Marcel Dekker; 1996. p. 285.Google Scholar
  30. 30.
    Avis KE, Lachman L. Theory and Practice of Industrial Pharmacy. 3rd ed. Bombay: Varghese publishing; 1976. p. 654.Google Scholar
  31. 31.
    Nash RA. Formulation of pharmaceutical suspension. Part I. Drug and Cosmetic Industry. 1965;97:843.Google Scholar

Copyright information

© Controlled Release Society 2015

Authors and Affiliations

  • Jaya Agnihotri
    • 1
    Email author
  • Shubhini Saraf
    • 2
  • Sobhna Singh
    • 3
  • Papiya Bigoniya
    • 4
  1. 1.H. K College of PharmacyMumbaiIndia
  2. 2.School of Biosciences & BiotechnologyBabasaheb Bhimrao Ambedkar UniversityLucknowIndia
  3. 3.School of Pharmaceutical SciencesMJP Rohilkhand UniversityBareillyIndia
  4. 4.Radharaman College of PharmacyBhopalIndia

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