AAPS PharmSciTech

, Volume 19, Issue 5, pp 2195–2202 | Cite as

Therapeutic Effect of a Novel Nano-Drug Delivery System on Membranous Glomerulonephritis Rat Model Induced by Cationic Bovine Serum

  • Xiumei Gai
  • Zhujun Jiang
  • Mengqi Liu
  • Qi Li
  • Shu Wang
  • Ting Li
  • Weisan Pan
  • Xinggang YangEmail author
Research Article


In order to explore a novel high efficacy drug delivery system for membranous glomerulonephritis (MGN), a complex chronic inflammation, methylprednisolone bovine serum albumin nanoparticles (ME BSA NPs) were designed. The nanoparticles were prepared by desolvation—chemical crosslinking method and its physicochemical characterizations were conducted. The experimental MGN rat models induced by cationic bovine serum albumin were established by a modified Border’s method and applied in the pharmacodynamics study of ME BSA NPs. The results showed that the particle size, particle dispersion index, and entrapment efficiency of ME BSA NPs were 131.1 ± 3.4 nm, 0.159 ± 0.036, and 71.51 ± 1.74%, respectively. In addition, the image of transmission electron microscopy showed that the ME BSA NPs were the relatively uniform spherical particles. In the in vivo pharmacodynamics study, compared with saline group and SOLU-MEDROL® group, that the ME BSA NPs group was significantly reduced the levels of 24 h urinary protein (P < 0.01) and serum creatinine (P < 0.05). Consequently, these outcomes indicated that the nanoparticles we studied were a promising drug delivery system for the MGN disease, and it may be also useful for other complex chronic inflammations.


bovine serum albumin nanoparticle methylprednisolone membranous glomerulonephritis chronic inflammation pharmacodynamics study 



This study was supported by the program of supporting career development of young and middle-aged teachers from Shenyang Pharmaceutical University (ZQN2015011).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Vezzani A, Ruegg S. The pivotal role of immunity and inflammatory processes in epilepsy is increasingly recognized: introduction. Epilepsia. 2011;52(Suppl 3):1–4. Scholar
  2. 2.
    Tabas I, Glass CK. Anti-inflammatory therapy in chronic disease: challenges and opportunities. Science. 2013;339(6166):166–72. Scholar
  3. 3.
    Nathan C. Points of control in inflammation. Nature. 2002;420(6917):846–52. Scholar
  4. 4.
    Azadegan-Dehkordi F, Bagheri N, Shirzad H, Rafieian-Kopaei M. The role of Th1 and Th17 cells in glomerulonephritis. Journal of nephropathology. 2015;4(2):32–7. PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Buraczynska M, Jozwiak L, Ksiazek P, Borowicz E, Mierzicki P. Interleukin-6 gene polymorphism and faster progression to end-stage renal failure in chronic glomerulonephritis. Translational research: the journal of laboratory and clinical medicine. 2007;150(2):101–5. Scholar
  6. 6.
    Santos FR. Membranous glomerulonephritis: new insights in pathophysiology and therapeutic approach. Jornal Brasileiro de Nefrologia. 2014;36(1):59–62. Scholar
  7. 7.
    Song J, Wang Y, Liu C, Huang Y, He L, Cai X, et al. Cordyceps militaris fruit body extract ameliorates membranous glomerulonephritis by attenuating oxidative stress and renal inflammation via the NF-kappaB pathway. Food Funct. 2016;7(4):2006–15.
  8. 8.
    Border WA, W HJ, Kamil ES, Cohen AH. Induction of membranous nephropathy in rabbits by administration of an exogenous cationic antigen. J Clin Invest. 1982;69(2):451–61. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Kerjaschki DF. M G. Immunocytochemical localization of the Heymann nephritis antigen (GP330) in glomerular epithelial cells of normal Lewis rats. J Exp Med. 1983;157(2):667–86. Scholar
  10. 10.
    Spies CM, Strehl C, van der Goes MC, Bijlsma JWJ, Buttgereit F. Glucocorticoids. Best Pract Res Clin Rheumatol. 2011;25(6):891–900. Scholar
  11. 11.
    He Y, Yi W, Suino-Powell K, Zhou XE, Tolbert WD, Tang X, et al. Structures and mechanism for the design of highly potent glucocorticoids. Cell Res. 2014;24(6):713–26.
  12. 12.
    Cho B-S, Park S-S, Kim S-D, Won KY, Lim S-J. Clinical and histologic response to methylprednisolone pulse therapy in glomerulonephritis. Fetal Pediatr Pathol. 2010;29(4):271–90. Scholar
  13. 13.
    Ou ZL, Nakayama K, Natori Y, Doi N, Saito T, Natori Y. Effective methylprednisolone dose in experimental crescentic glomerulonephritis. Am J Kidney Dis: Off J Natl Kidney Foundation. 2001;37(2):411–7. Scholar
  14. 14.
    Schäcke H, Döcke WD, Asadullah K. Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther. 2002;96(1):23–43.
  15. 15.
    Wang Z, Tiruppathi C, Cho J, Minshall RD, Malik AB. Delivery of nanoparticle: complexed drugs across the vascular endothelial barrier via caveolae. IUBMB Life. 2011;63(8):659–67. Scholar
  16. 16.
    Dafeng Chu JG, Wang Z. Neutrophil-mediated delivery of therapeutic nanoparticles across blood vessel barrier for treatment of inflammation and infection. ACS Nano. 2015;9:11800–11. Scholar
  17. 17.
    Wang Z, Li J, Cho J, Malik AB. Prevention of vascular inflammation by nanoparticle targeting of adherent neutrophils. Nat Nanotechnol. 2014;9(3):204–10. Scholar
  18. 18.
    Hsu LC, Enzler T, Seita J, Timmer AM, Lee CY, Lai TY, et al. IL-1beta-driven neutrophilia preserves antibacterial defense in the absence of the kinase IKKbeta. Nat Immunol. 2011;12(2):144–50.
  19. 19.
    Wilhelmsen K, Mesa KR, Prakash A, Xu F, Hellman J. Activation of endothelial TLR2 by bacterial lipoprotein upregulates proteins specific for the neutrophil response. Innate Immun. 2012;18(4):602–16. Scholar
  20. 20.
    Pillay J, Hietbrink F, Koenderman L, Leenen LP. The systemic inflammatory response induced by trauma is reflected by multiple phenotypes of blood neutrophils. Injury. 2007;38(12):1365–72. Scholar
  21. 21.
    Weber C, K J, Langer K. Desolvation process and surface characteristics of HSA-nanoparticles. Int J Pharm. 2000;196(2):197–200. CrossRefPubMedGoogle Scholar
  22. 22.
    Galisteo-Gonzalez F, Molina-Bolivar JA. Systematic study on the preparation of BSA nanoparticles. Colloids Surf B: Biointerfaces. 2014;123:286–92. Scholar
  23. 23.
    Yedomon B, Fessi H, Charcosset C. Preparation of bovine serum albumin (BSA) nanoparticles by desolvation using a membrane contactor: a new tool for large scale production. European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik eV. 2013;85(3 Pt a):398–405. Scholar
  24. 24.
    Gao J, Zhang T, Kang Z, Ting W, Xu L, Yin D. The F0F1 ATP synthase regulates human neutrophil migration through cytoplasmic proton extrusion coupled with ATP generation. Mol Immunol. 2017;90:219–26. Scholar
  25. 25.
    Crouser ED, Shao G, Julian MW, Macre JE, Shadel GS, Tridandapani S, et al. Monocyte activation by necrotic cells is promoted by mitochondrial proteins and formyl peptide receptors. Crit Care Med. 2009;37(6):2000–9.
  26. 26.
    Silva MT. When two is better than one: macrophages and neutrophils work in concert in innate immunity as complementary and cooperative partners of a myeloid phagocyte system. J Leukoc Biol. 2009;87(1):93–106. Scholar
  27. 27.
    Kobayashi M, M K, Yoh K, Kondoh M, Iwabuchi S, Hirayama K, et al. Effects of FK506 on experimental membranous glomerulonephritis induced by cationized bovine serum albumin in rats. Nephrol Dial Transplant. 1998;13(10):2501–8.
  28. 28.
    Zhang S, Xin H, Li Y, Zhang D, Shi J, Yang J, et al. Skimmin, a coumarin from Hydrangea paniculata, slows down the progression of membranous glomerulonephritis by anti-inflammatory effects and inhibiting immune complex deposition. Evid Based Complement Alternat Med: eCAM. 2013;2013:819296. Scholar
  29. 29.
    Rohiwal SS, Satvekar RK, Tiwari AP, Raut AV, Kumbhar SG, Pawar SH. Investigating the influence of effective parameters on molecular characteristics of bovine serum albumin nanoparticles. Appl Surf Sci. 2015;334:157–64. Scholar
  30. 30.
    Salis A, Bostrom M, Medda L, Cugia F, Barse B, Parsons DF, et al. Measurements and theoretical interpretation of points of zero charge/potential of BSA protein. Langmuir: ACS J Surf Colloids. 2011;27(18):11597–604. CrossRefGoogle Scholar
  31. 31.
    Wacker M. Nanocarriers for intravenous injection—the long hard road to the market. Int J Pharm. 2013;457(1):50–62. Scholar
  32. 32.
    Yokomori H, Oda M, Yoshimura K, Hibi T. Recent advances in liver sinusoidal endothelial ultrastructure and fine structure immunocytochemistry. Micron. 2012;43(2–3):129–34. Scholar
  33. 33.
    Hoshino Y, K H, Furuya K, Haberaecker WW, Lee SH, Kodama T, et al. The rational design of a synthetic polymer nanoparticle that neutralizes a toxic peptide in vivo. Proc Natl Acad Sci U S A. 2012;109(1):33–8.
  34. 34.
    Matar HE, Peterson P, Sangle S, D'Cruz DP. Correlation of 24-hour urinary protein quantification with spoturine protein:creatinine ratio in lupus nephritis. Lupus. 2012;21(8):836–9. CrossRefPubMedGoogle Scholar
  35. 35.
    Ronco P, Debiec H. Pathogenesis of membranous nephropathy: recent advances and future challenges. Nat Rev Nephrol. 2012;8(4):203–13. Scholar
  36. 36.
    Shankland SJ. New insights into the pathogenesis of membranous nephropathy. Kidney Int. 2000;57(3):1204–5. Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Xiumei Gai
    • 1
  • Zhujun Jiang
    • 1
  • Mengqi Liu
    • 2
  • Qi Li
    • 1
  • Shu Wang
    • 1
  • Ting Li
    • 1
  • Weisan Pan
    • 1
  • Xinggang Yang
    • 1
    Email author
  1. 1.Department of Pharmaceutics, School of Pharmaceutical SciencesShenyang Pharmaceutical UniversityShenyangChina
  2. 2.Department of Traditional Chinese MedicineShenyang Pharmaceutical UniversityShenyangChina

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