Advertisement

Shape mediated splenotropic delivery of buparvaquone loaded solid lipid nanoparticles

  • Heena V. Maithania
  • Bhabani S. Mohanty
  • Pradip R. Chaudhari
  • Abdul Samad
  • Padma V. DevarajanEmail author
Original Article
First Online:

Abstract

Buparvaquone (BPQ)–loaded asymmetric solid lipid nanoparticles (SLN) prepared by a modified nanoprecipitation method were evaluated for splenotropic drug delivery. BPQ SLN exhibited an average particle size of 650.28 ± 6.75 nm with polydispersity index ≤ 0.3, entrapment efficiency of 96.57 ± 0.190%, and drug loading of 24.63 ± 0.042%. Scanning electron microscopy (SEM) revealed elongated particles with flattened and rounded edges. Aspect ratio, an important determinant of asymmetricity of the BPQ SLN, measured as the ratio of average length (1143 ± 0.083 nm) to width (419 ± 0.031 nm) was found to be 2.727 ± 0.19. The hemolytic potential of 10.86 ± 0.04% and good serum stability suggested feasibility for intravenous administration. 99mTc-labeled BPQ SLN revealed high radiolabeling efficiency (> 95%) and good stability. Intravenous administration in mice revealed > 75% accumulation in the reticuloendothelial system organs. The percent radioactivity per gram of organ was in the order spleen > kidney > lungs > liver > lymph nodes, with high splenic accumulation and significantly lower concentration in the liver. An astoundingly high spleen/liver ratio with a maximum of 11.94 ± 1.37 at 3 h, which confirmed high splenic uptake is attributed to Kupffer cell bypass. Other factors contributing to splenotropy are the rigidity and the low molecular weight of the lipid in the BPQ SLN which enabled translocation of the particles into the splenic pulp. Our study proposes asymmetric BPQ SLN as a promising splenotropic delivery system for improved efficacy in theileriosis, a spleen resident infection.

Keywords

Solid lipid nanoparticles Splenotropy Gamma scintigraphy Asymmetric shape Splenic uptake Buparvaquone 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

Heena V. Maithania is thankful to University Grants Commission- Special Assistance Program (UGC-SAP) for providing senior research fellowship and Sotax India Pvt. Ltd. for USP apparatus IV.

Compliance with ethical standards

The manuscript entitled “Shape mediated splenotropic delivery of buparvaquone loaded solid lipid nanoparticles” complies with the current laws of India.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Muraguri GR, Ngumi PN, Wesonga D, Ndungu SG, Wanjohi JM, Bang K, et al. Clinical efficacy and plasma concentrations of two formulations of buparvaquone in cattle infected with East Coast fever (Theileria Parva infection). Res Vet Sci. 2006;81:119–26.CrossRefPubMedGoogle Scholar
  2. 2.
    Shkap V, Leibovich B, Krigel Y, Lea F, Orgad U. Evaluation of the combined formulation of parvaquone and frusemide (Fruvexon) in the treatment of experimental tropical theileriosis. Intern J Appl Res Vet Med. 2010;8(1):73–7.Google Scholar
  3. 3.
    Campbell JDM, Brown DJ, Nichani AK, Howie SEM, Spooner RL, Glass EJ. A non-protective T helper 1 response against the intra-macrophage protozoan Theileria annulata. Clin Exp Immunol. 1997;108:463–70.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Altug N, Yuksek N, Agaoglu ZT, Keles I. Determination of adenosine deaminase activity in cattle naturally infected with Theileria annulata. Trop Anim Health Prod. 2008;40:449–56.CrossRefPubMedGoogle Scholar
  5. 5.
    Preston PM, Jackson LA, Sutherland IA, Brown DJ, Schofield J, Bird T, et al. Theileria annulata: attenuation of a Schizont-infected cell line by prolonged in vitro culture is not caused by the preferential growth of particular host cell types. Exp Parasitol. 2001;98:188–205.CrossRefPubMedGoogle Scholar
  6. 6.
    Chen LT, Weiss L. The role of the sinus wall in the passage of erythrocytes through the spleen. Blood. 1973;41:529–37.CrossRefPubMedGoogle Scholar
  7. 7.
    Tabata Y, Ikada Y. Phagocytosis of polymer microspheres by macrophages. Adv Polym Sci. 1990;94:107–41.CrossRefGoogle Scholar
  8. 8.
    Stolnik S, Illum L, Davis SS. Long circulating microparticulate drug carriers. Adv Drug Deliv Rev. 1995;16(2–3):195–214.CrossRefGoogle Scholar
  9. 9.
    Mathaes R, Winter G, Besheer A, Engert J. Influence of particle geometry and PEGylation on phagocytosis of particulate carriers. Int J Pharm. 2014;465:159–64.CrossRefPubMedGoogle Scholar
  10. 10.
    Almeida JPM, Chen AL, Foster A, Drezek R. In vivo biodistribution of nanoparticles. Nanomedicine. 2011;6(5):815–35.CrossRefPubMedGoogle Scholar
  11. 11.
    Moghimi SM. Mechanisms of splenic clearance of blood cells and particles: towards development of new splenotropic agents. Adv Drug Deliv Rev. 1995;17:103–15.CrossRefGoogle Scholar
  12. 12.
    Jindal AB. Nanocarriers for spleen targeting: anatomo-physiological considerations, formulation strategies and therapeutic potential. Drug Deliv Transl Res. 2016;6(5):473–85.CrossRefPubMedGoogle Scholar
  13. 13.
    Harris BJ, Dalhaimer P. Particle shape effects in vitro and in vivo. Front Biosci. 2012;1(4):1344–53.Google Scholar
  14. 14.
    Huang X, El-Sayed IH, Qian W, El-Sayed MA. Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. J Am Chem Soc. 2006;128:2115–20.CrossRefPubMedGoogle Scholar
  15. 15.
    Toy R, Peiris PM, Ghaghada KB, Karathanasis E. Shaping Cancer Nanomedicine. The effect of particle shape on the in vivo journey of nanoparticles. Nanomedicine. 2014;9(1):121–34.CrossRefPubMedGoogle Scholar
  16. 16.
    Chithrani BD, Ghazani AA, Chan WC. Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett. 2006;6(4):662–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Sharma G, Valenta DT, Altman Y, Harvey S, Xie H, Mitragotri S, et al. Polymer particle shape independently influences binding and internalization by macrophages. J Control Release. 2010;147(3):408–12.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Geng Y, Dalhaimer P, Cai S, et al. Shape effects of filaments versus spherical particles in flow and drug delivery. Nat Nanotechnol. 2007;2(4):249–55.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Champion JA, Mitragotri S. Role of target geometry in phagocytosis. Proc Natl Acad Sci. 2006;103(13):4930–4.CrossRefPubMedGoogle Scholar
  20. 20.
    Decuzzi P, Godin B, Tanaka T, Lee S-Y, Chiappini C, Liu X, et al. Size and shape effects in the biodistribution of intravascularly injected particles. J Control Release. 2010;141:320–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Kaga S, Truong NP, Esser L, Senyschyn D, Sanyal A, Sanyal R, et al. Influence of size and shape on the biodistribution of nanoparticles prepared by polymerization-induced self-assembly (PISA). Biomacromolecules. 2017;18(2):3963–70.CrossRefPubMedGoogle Scholar
  22. 22.
    Black KCL, Wang Y, Luehmann HP, Cai X, Xing W, Pang B, et al. Radioactive 198Au-doped nanostructures with different shapes for in vivo analyses of their biodistribution, tumor uptake, and intratumoral distribution. ACS Nano. 2014;8(5):4385–94.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Gratton SEA, Ropp PA, Pohlhaus PD, Luft JC, Madden VJ, Napier ME, et al. The effect of particle design on cellular internalization pathways. Proc Natl Acad Sci. 2008;105:11613–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Mitragotri S, Lahann J. Physical approaches to biomaterial design. Nat Mater. 2009;8:15–23.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Doshi N, Mitragotri S. Macrophages recognize size and shape of their targets. PLoS One. 2010;5(4):e10051.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Lee SY, Ferrari M, Decuzzi P. Shaping nano/microparticles for enhanced vascular interaction in laminar flows. Nanotechnology. 2009;20:1–11.Google Scholar
  27. 27.
    Champion JA, Katare YK, Mitragotri S. Particle shape: a new design parameter for micro- and nanoscale drug delivery carriers. J Control Release. 2007;121:3–9.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Blanco E, Shen H, Ferrari M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol. 2015;33(9):941–51.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Klibanov AL, Maruyama K, Beckerleg AM, Torchilin VP, Huang L. Activity of amphipathic poly(ethylene glycol) 5000 to prolong the circulation time of liposomes depends on the liposome size and is unfavorable for immunoliposome binding to target. Biochim Biophys Acta. 1991;1062:142–8.CrossRefPubMedGoogle Scholar
  30. 30.
    Huang X, Xu T, Dong C, Tang F, He J. The effect of the shape of mesoporous silica nanoparticles on cellular uptake and cell function. Biomaterials. 2010;31:438–48.CrossRefPubMedGoogle Scholar
  31. 31.
    Moghimi SM, Porter CJ, Muir IS, Illum L, Davis SS. Non-phagocytic uptake of intravenously injected microspheres in rat spleen: influence of particle size and hydrophilic coating. Biochem Biophys Res Commun. 1991;177:861–6.CrossRefPubMedGoogle Scholar
  32. 32.
    Moghimi SM, Hedeman H, Muir IS, Illum L, Davis SS. An investigation of the filtration capacity and the fate of large filtered sterically-stabilized microspheres in rat spleen. Biochim Biophys Acta. 1993;1157:233–40.CrossRefPubMedGoogle Scholar
  33. 33.
    Peracchia MT, Fattal E, Desmaële D, Besnard M, Noël JP, Gomis JM, et al. Stealth PEGylated polycyanoacrylate nanoparticles for intravenous administration and splenic targeting. J Control Release. 1999;60:121–8.CrossRefPubMedGoogle Scholar
  34. 34.
    Liang C, Yang Y, Ling Y, Huang Y, Li T, Li X. Improved therapeutic effect of folate-decorated PLGA-PEG nanoparticles for endometrial carcinoma. Bioorg Med Chem. 2011;19:4057–66.CrossRefPubMedGoogle Scholar
  35. 35.
    Litzinger DC, Huang L. Amphipathic poly(ethylene glycol) 5000- stabilized dioleoylphosphatidylethanolamine liposomes accumulate in spleen. Biochim Biophys Acta (BBA)/Lipids Lipid Metab. 1992;1127:249–54.CrossRefGoogle Scholar
  36. 36.
    Moghimi SM, Patel HM. Tissue specific opsonins for phagocytic cells and their affinity for cholesterol rich liposomes. FEBS Lett. 1988;233:143–7.CrossRefPubMedGoogle Scholar
  37. 37.
    Patil RR, Gaikwad RV, Samad A, Devarajan PV. Role of lipids in enhancing splenic uptake of polymer-lipid (LIPOMER) nanoparticles. J Biomed Nanotechnol. 2008;4(3):359–66.CrossRefGoogle Scholar
  38. 38.
    Devarajan PV, Jindal AB, Patil RR, Mulla F, Gaikwad RV, Samad A. Particle shape: a new design parameter for passive targeting in splenotropic drug delivery. J Pharm Sci. 2010;99(6):2576–81.CrossRefPubMedGoogle Scholar
  39. 39.
    Soni MP, Shelkar N, Gaikwad RV, Vanage GR, Samad A, Devarajan PV. Buparvaquone loaded solid lipid nanoparticles for targeted delivery in theleriosis. J Pharm Bioall Sci. 2014;6(1):22–30.CrossRefGoogle Scholar
  40. 40.
    Fessi H, Puisieux F, Devissaguet JP, Ammoury N, Benita S. Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int J Pharm. 1989;55(1):R1–4.CrossRefGoogle Scholar
  41. 41.
    Bhardwaj U, Burgess DJ. A novel USP apparatus 4 based release testing method for dispersed systems. Int J Pharm. 2010;388:287–94.CrossRefPubMedGoogle Scholar
  42. 42.
    Chen W, Gua B, Hao W, Pan J, Lua W, Hou H. Development and evaluation of novel itraconazole-loaded intravenous nanoparticles. Int J Pharm. 2008;362:133–40.CrossRefPubMedGoogle Scholar
  43. 43.
    Garg M, Garg BR, Jain S, Mishra P, Sharma RK, Mishra AK, et al. Radiolabeling, pharmacoscintigraphic evaluation and antiretroviral efficacy of stavudine loaded 99mTc labeled galactosylated liposomes. Eur J Pharm Biopharm. 2008;33(3):271–81.Google Scholar
  44. 44.
    Banerjee T, Singh AK, Sharma RK, Maitra AN. Labelling efficiency and biodistribution of technetium-99m labeled nanoparticles: interference by colloidal tin oxide particles. Int J Pharm. 2005;289:189–95.CrossRefPubMedGoogle Scholar
  45. 45.
    Dobrovolskaia MA, Clogston JD, Neun BW, Hall JB, Patri AK, McNeil SE. Method for analysis of nanoparticle hemolytic properties in vitro. Nano Lett. 2008;8(8):2180–7.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Krzyzaniak JF, Yalkowsky SH. Lysis of human red blood cells. Effect of contact time on surfactant-induced hemolysis. J Pharm Sci and Technol. 1998;52:66–9.Google Scholar
  47. 47.
    Han HD, Shin BC, Choi HS. Doxorubicin-encapsulated thermosensitive liposomes modified with poly(N-isopropylacrylamide-co-acrylamide): drug release behavior and stability in the presence of serum. Eur J Pharm Biopharm. 2006;62:110–6.CrossRefPubMedGoogle Scholar
  48. 48.
    Alexis F, Pridgen E, Molnar LK, Farokhzad OC. Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm. 2008;5:505–15.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Atkins H, Richards P. Assessment of thyroid function and anatomy with technetium -99m as pertechnetate. J Nucl Med. 1967;9(1):1–10.Google Scholar
  50. 50.
    Kapse SV, Gaikwad RV, Samad A, Devarajan PV. Self nanoprecipitating preconcentrate of tamoxifen citrate for enhanced bioavailability. Int J Pharm. 2012;429:104–12.CrossRefPubMedGoogle Scholar
  51. 51.
    Patel MD, Date PV, Gaikwad RV, Samad A, Malshe VC, Devarajan PV. Comparative evaluation of polymeric nanoparticles of rifampicin comprising Gantrez and poly(ethylene sebacate) on pharmacokinetics, biodistribution and lung uptake following oral administration. J Biomed Nanotechnol. 2013;9:1–8.CrossRefGoogle Scholar
  52. 52.
    Guhagarkar SA, Gaikwad RV, Samad A, Malshe VC, Devarajan PV. Polyethylene sebacate-doxorubicin nanoparticles for hepatic targeting. Int J Pharm. 2010;401:113–22.CrossRefPubMedGoogle Scholar
  53. 53.
    D’Souza AA, Jain P, Galdhar CN, Samad A, Degani MS, Devarajan PV. Comparative in silico-in vivo evaluation of ASGP-R ligands for hepatic targeting of curcumin Gantrez nanoparticles. AAPS J 2013; 1–11.Google Scholar
  54. 54.
    Aggarwal P, Hall JB, McLeland CB, Dobrovolskaia MA, McNeil SE. Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. Adv Drug Deliv Rev. 2009;61:428–37.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Aderem A, Underhill DM. Mechanisms of phagocytosis in macrophages. Annu Rev Immunol. 1999;17:593–623.CrossRefPubMedGoogle Scholar
  56. 56.
    Nolte MA, Beliën JAM, Schadee-Eestermans I, Jansen W, Unger WWJ, van Rooijen N, Kraal G, Mebius RE. A conduit system distributes chemokines and small blood-borne molecules through the splenic white pulp. J Exp Med 2015, 505–512.Google Scholar
  57. 57.
    Paul D, Achouri S, Yoon Y-Z, Herre J, Bryant CE, Cicuta P. Phagocytosis dynamics depends on target shape. Biophys J. 2013;105(5):1143–50.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Champion JA, Katare YK, Mitragotri S. Making polymeric micro- and nanoparticles of complex shapes. Proc Natl Acad Sci. 2007;104:11901–4.CrossRefPubMedGoogle Scholar
  59. 59.
    Mebius RE, Kraal G. Structure and function of the spleen. Nat Rev Immunol. 2005;5:606–16.CrossRefPubMedGoogle Scholar
  60. 60.
    Zhang L, Cao Z, Li Y, Ella-Menye J-R, Bai T, Jiang S. Softer zwitterionic nanogels for longer circulation and lower splenic accumulation. ACS Nano. 2012;6(8):6681–6.CrossRefPubMedGoogle Scholar

Copyright information

© Controlled Release Society 2019

Authors and Affiliations

  1. 1.Department of Pharmaceutical Sciences & Technology, Institute of Chemical Technology, Elite status and Centre of ExcellenceDeemed UniversityMumbaiIndia
  2. 2.Comparative Oncology Program and Small Animal Imaging Facility, Advanced Centre for Treatment, Education and Research in CancerTata Memorial CentreNavi MumbaiIndia
  3. 3.Bombay Veterinary CollegeMumbaiIndia

Personalised recommendations

Cite article

Buy options