Volume 22, Issue 1 (2019)                   MJMS 2019, 22(1): 7-19 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Vasegh R, Ebtekar M, Shafiee Ardestani M, Gholamzad M. Comparison of Humoral and Cell-Mediated Immune Response to Tetanustoxin Coated PLGA in Mice. MJMS. 2019; 22 (1) :7-19
URL: http://journals.modares.ac.ir/article-30-17876-en.html
1- Immunology Department, Medical Sciences Faculty, Tarbiat Modares University, Tehran, Iran
2- Immunology Department, Medical Sciences Faculty, Tarbiat Modares University, Tehran, Iran , ebtekarm@modares.ac.ir
3- Radiopharmacy Department, Pharmacy Faculty, Tehran University of Medical Sciences, Tehran, Iran
Abstract:   (122 Views)
Aims: New vaccines based on recombinant and DNA proteins are safer than traditional vaccines, but unfortunately, they have lower Therefore, there is a need for the development of safe and strong that can increase the immune PLGA), ester, consists of acidic and lactic acid. Its hydrolysis leads to the production of lactic acid and glycolic acid monomers. The aim of this study was to compare humoral and cell mediated immune response to coated PLGA in mice.
Materials and Methods: In this experimental study, PLGA nanoparticles were produced by water/oil (W/O) method. Tetanus toxin attached to by EDC. After coated characterization, they were injected into different groups of mice. The complete and Alum as After a single injection, the of was investigated by ELISA and cellular analyzed by spleen cell proliferation assay. One-way analysis of variance was used.
Findings: PLGA nanoparticles had a strong effect, and when used with antigens, could produce cellular and humoral immune response far more powerful than alum and than Freund’s adjuvant.
Conclusion: Glycolic polyester, in the form of conjugation with an antigen, can be used to increase the immune response, especially in the cellular immune arm, relative to the antigenic solution. Although PLGA seems not so successful to the humoral immune stimulus against in comparison to the full of it can be a significant competitor with
Full-Text [PDF 1334 kb]   (70 Downloads)    

Received: 2018/03/18 | Accepted: 2018/06/12 | Published: 2019/03/11

1. Sivakumar SM, Safhi MM, Kannadasan M, Sukumaran N. Vaccine adjuvants-current status and prospects on controlled release adjuvancity. Saudi Pharm J. 2011;19(4):197-206. [Link] [DOI:10.1016/j.jsps.2011.06.003]
2. Diwan M, Elamanchili P, Cao M, Samuel J. Dose sparing of CpG Oligodeoxynucleotide vaccine adjuvants by nanoparticle delivery. Curr Drug Deliv. 2004;1(4):405-12. [Link] [DOI:10.2174/1567201043334597]
3. Pihlajamäki H, Böstman O, Hirvensalo E, Törmälä P, Rokkanen P. Absorbable pins of self-reinforced poly-L-lactic acid for fixation of fractures and osteotomies. J Bone Joint Surg Br. 1992;74(6):853-7. [Link] [DOI:10.1302/0301-620X.74B6.1447246]
4. Jagur-Grodzinski J. Biomedical application of functional polymers. React Funct Polym. 1999;39(2):99-138. [Link] [DOI:10.1016/S1381-5148(98)00054-6]
5. Wendorf J, Chesko J, Kazzaz J, Ugozzoli M, Vajdy M, O'Hagan D, et al. A comparison of anionic nanoparticles and microparticles as vaccine delivery systems. Hum Vaccin. 2008;4(1):44-9. [Link] [DOI:10.4161/hv.4.1.4886]
6. Arshady R. Preparation of biodegradable microspheres and microcapsules: 2, Polyactides and related polyesters. J Control Release. 1991;17(1):1-21. [Link] [DOI:10.1016/0168-3659(91)90126-X]
7. Chaisri W, Hennink WE, Okonogi S. Preparation and characterization of cephalexin loaded PLGA microspheres. Curr Drug Deliv. 2009;6(1):69-75. [Link] [DOI:10.2174/156720109787048186]
8. Roberts JC, Bhalgat MK, Zera RT. Preliminary biological evaluation of polyamidoamine (PAMAM) Starburst dendrimers. J Biomed Mater Res. 1996;30(1):53-65. https://doi.org/10.1002/(SICI)1097-4636(199601)30:1<53::AID-JBM8>3.0.CO;2-Q [Link] [DOI:10.1002/(SICI)1097-4636(199601)30:13.0.CO;2-Q]
9. Agashe HB, Dutta T, Garg M, Jain NK. Investigations on the toxicological profile of functionalized fifth-generation poly (propylene imine) dendrimer. J Pharm Pharmacol. 2006;58(11):1491-8. [Link] [DOI:10.1211/jpp.58.11.0010]
10. Andreev SM, Babakhin AA, Petrukhina AO, Romanova VS, Parnes ZN, Petrov RV. Immunogenic and allergenic properties of fulleren conjugates with aminoacids and proteins. Dokl Biochem. 2000;370(1-6):4-7. [Link]
11. Masalova OV, Shepelev AV, Atanadze SN, Parnes ZN, Romanova VS, Vol'pina OM, et al. Immunostimulating effect of water-soluble fullerene derivatives--perspective adjuvants for a new generation of vaccine. Dokl Akad Nauk. 1999;369(3):411-3. [Russian] [Link]
12. Zolnik BS, González-Fernández A, Sadrieh N, Dobrovolskaia MA. Nanoparticles and the immune system. Endocrinology. 2010;151(2):458-65. [Link] [DOI:10.1210/en.2009-1082]
13. Xiang SD, Scholzen A, Minigo G, David C, Apostolopoulos V, Mottram PL, et al. Pathogen recognition and development of particulate vaccines: Does size matter? Methods. 2006;40(1):1-9. [Link] [DOI:10.1016/j.ymeth.2006.05.016]
14. Foged C, Brodin B, Frokjaer S, Sundblad A. Particle size and surface charge affect particle uptake by human dendritic cells in an in vitro model. Int J Pharm. 2005;298(2):315-22. [Link] [DOI:10.1016/j.ijpharm.2005.03.035]
15. Joshi VB, Geary SM, Salem AK. Biodegradable particles as vaccine delivery systems: Size matters. AAPS J. 2013;15(1):85-94. [Link] [DOI:10.1208/s12248-012-9418-6]
16. Kim H, Uto T, Akagi T, Baba M, Akashi M. Amphiphilic poly(amino acid) nanoparticles induce size-dependent dendritic cell maturation. Adv Funct Mater. 2010;20(22):3925-31. [Link] [DOI:10.1002/adfm.201000021]
17. Nicolete R, dos Santos DF, Faccioli LH. The uptake of PLGA micro or nanoparticles by macrophages provokes distinct in vitro inflammatory response. Int Immunopharmacol. 2011;11(10):1557-63. [Link] [DOI:10.1016/j.intimp.2011.05.014]
18. 18 - Patel NR, Damann K, Leonardi C, Sabliov CM. Size dependency of PLGA-nanoparticle uptake and antifungal activity against Aspergillus flavus. Nanomedicine. 2011;6(8):1381-95. [Link] [DOI:10.2217/nnm.11.35]
19. Chithrani BD, Ghazani AA, Chan WCW. Determining the size and shape dependence of Gold nanoparticle uptake into mammalian cells. Nano Lett. 2006;6(4):662-8. [Link] [DOI:10.1021/nl052396o]
20. Champion JA, Mitragotri S. Shape induced inhibition of phagocytosis of polymer particles. Pharm Res. 2009;26(1):244-9. [Link] [DOI:10.1007/s11095-008-9626-z]
21. Niikura K, Matsunaga T, Suzuki T, Kobayashi S, Yamaguchi H, Orba Y, et al. Gold nanoparticles as a vaccine platform: Influence of size and shape on immunological responses in vitro and in vivo. ACS Nano. 2013;7(5):3926-38. [Link] [DOI:10.1021/nn3057005]
22. Yoo JW, Doshi N, Mitragotri S. Endocytosis and intracellular distribution of PLGA particles in endothelial cells: Effect of particle Geometry. Macromol Rapid Commun. 2010;31(2):142-8. [Link]
23. Mu-oz Javier A, Kreft O, Piera Alberola A, Kirchner C, Zebli B, Susha AS, et al. Combined atomic force microscopy and optical microscopy measurements as a method to investigate particle uptake by cells. Small. 2006;2(3):394-400. [Link] [DOI:10.1002/smll.200500282]
24. Harush-Frenkel O, Rozentur E, Benita S, Altschuler Y. Surface charge of nanoparticles determines their endocytic and transcytotic pathway in polarized MDCK cells. Biomacromolecules. 2008;9(2):435-43. [Link] [DOI:10.1021/bm700535p]
25. Jiang G, Tang Sh, Xuelan C, Ding F. Enhancing the receptor-mediated cell uptake of PLGA nanoparticle for targeted drug delivery by incorporation chitosan onto the particle surface. J Nanopart Res. 2014;16(6):2453. [Link] [DOI:10.1007/s11051-014-2453-8]
26. Hillaireau H, Couvreur P. Nanocarriers' entry into the cell: Relevance to drug delivery. Cell Mol Life Sci. 2009;66(17):2873-96. [Link] [DOI:10.1007/s00018-009-0053-z]
27. Raghuvanshi RS, Katare YK, Lalwani K, Ali MM, Singh O, Panda AK. Improved immune response from biodegradable polymer particles entrapping tetanus toxoid by use of different immunization protocol and adjuvants. Int J Pharm. 2002;245(1-2):109-21. [Link] [DOI:10.1016/S0378-5173(02)00342-3]
28. Samadi Moghaddam M, Heiny M, Shastri VP. Enhanced cellular uptake of nanoparticles by increasing the hydrophobicity of poly(lactic acid) through copolymerization with cell-membrane-lipid components. Chem Commun. 2015;51(78):14605-8. [Link] [DOI:10.1039/C5CC06397C]
29. Harandi AM, Medaglini D, Shattock RJ. Vaccine adjuvants: A priority for vaccine research. Vaccine. 2010;28(12):2363-6. [Link] [DOI:10.1016/j.vaccine.2009.12.084]
30. Tan Y, Li S, Pitt BR, Huang L. The inhibitory role of CpG immunostimulatory motifs in cationic lipid vector-mediated transgene expression in vivo. Hum Gene Ther. 1999;10(13):2153-61. [Link] [DOI:10.1089/10430349950017149]
31. Cui Z, Han SJ, Vangasseri DP, Huang L. Immunostimulation mechanism of LPD nanoparticle as a vaccine carrier. Mol Pharm. 2005;2(1):22-8. [Link] [DOI:10.1021/mp049907k]
32. Kumar A, Wonganan P, Sandoval MA, Li X, Zhu S, Cui Z. Microneedle-mediated transcutaneous immunization with plasmid DNA coated on cationic PLGA nanoparticles. J Control Release. 2012;163(2):230-9. [Link] [DOI:10.1016/j.jconrel.2012.08.011]
33. Wang G, Pan L, Zhang Y, Wang Y, Zhang Z, Lü J, et al. Intranasal delivery of cationic PLGA nano/microparticles-loaded FMDV DNA vaccine encoding IL-6 elicited protective immunity against FMDV challenge. PLoS One. 2011;6(11):e27605. [Link] [DOI:10.1371/journal.pone.0027605]
34. Saini V, Jain V, Sudheesh MS, Jaganathan KS, Murthy PK, Kohli DV. Comparison of humoral and cell-mediated immune responses to cationic PLGA microspheres containing recombinant hepatitis B antigen. Int J Pharm. 2011;408(1-2):50-7. [Link] [DOI:10.1016/j.ijpharm.2011.01.045]
35. Nabeshi H, Yoshikawa T, Arimori A, Yoshida T, Tochigi S, Hirai T, et al. Effect of surface properties of silica nanoparticles on their cytotoxicity and cellular distribution in murine macrophages. Nanoscale Res Lett. 2011;6(1):1-6. [Link] [DOI:10.1186/1556-276X-6-93]
36. Jacobsen NR, Møller P, Jensen KA, Vogel U, Ladefoged O, Loft S, et al. Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE-/-mice. Part Fibre Toxicol. 2009;6:2. [Link] [DOI:10.1186/1743-8977-6-2]
37. Pulskamp K, Diabaté S, Krug HF. Carbon nanotubes show no sign of acute toxicity but induce intracellular reactive oxygen species in dependence on contaminants. Toxicol Lett. 2007;168(1):58-74. [Link] [DOI:10.1016/j.toxlet.2006.11.001]
38. Müller K, Skepper JN, Posfai M, Trivedi R, Howarth S, Corot C, et al. Effect of ultrasmall superparamagnetic Iron oxide nanoparticles (Ferumoxtran-10) on human monocyte-macrophages in vitro. Biomaterials. 2007;28(9):1629-42. [Link] [DOI:10.1016/j.biomaterials.2006.12.003]
39. Linhart W, Peters F, Lehmann W, Schwarz K, Schilling AF, Amling M, et al. Biologically and chemically optimized composites of carbonated apatite and polyglycolide as bone substitution materials. J Biomed Mater Res. 2001;54(2):162-71. https://doi.org/10.1002/1097-4636(200102)54:2<162::AID-JBM2>3.0.CO;2-3 [Link] [DOI:10.1002/1097-4636(200102)54:23.0.CO;2-3]
40. Ara M, Watanabe M, Imai Y. Effect of blending Calcium compounds on hydrolytic degradation of poly(DL-lactic acid-co-glycolic acid). Biomaterials. 2002;23(12):2479-83. [Link] [DOI:10.1016/S0142-9612(01)00382-9]
41. Kim S, Lee Y, Park H, Hong D, Khang G, Lee D. Reduced inflammatory responses to poly(lactic-co-glycolic acid) by the incorporation of hydroxybenzyl alcohol releasing polyoxalate. Macromol Res. 2011;19(12):1242-9. [Link] [DOI:10.1007/s13233-011-1215-z]
42. Lee Y, Kwon J, Khang G, Lee D. Reduction of inflammatory responses and enhancement of extracellular matrix formation by vanillin-incorporated poly(lactic-co-glycolic acid) scaffolds. Tissue Eng Part A. 2012;18(19-20):1967-78. [Link] [DOI:10.1089/ten.tea.2012.0001]
43. Lutsiak ME, Kwon GS, Samuel J. Biodegradable nanoparticle delivery of a Th2-biased peptide for induction of Th1 immune responses. J Pharm Pharmacol. 2006;58(6):739-47. [Link] [DOI:10.1211/jpp.58.6.0004]
44. Jung T, Kamm W, Breitenbach A, Hungerer KD, Hundt E, Kissel T. Tetanus toxoid loaded nanoparticles from sulfobutylated poly(vinyl alcohol)-graft-poly(lactide-co-glycolide): Evaluation of antibody response after oral and nasal application in mice. Pharm Res. 2001;18(3):352-60. [Link] [DOI:10.1023/A:1011063232257]
45. Mottram PL, Leong D, Crimeen-Irwin B, Gloster S, Xiang SD, Meanger J, et al. Type 1 and 2 immunity following vaccination is influenced by nanoparticle size:  Formulation of a model vaccine for respiratory syncytial virus. Mol Pharm. 2007;4(1):73-84. [Link] [DOI:10.1021/mp060096p]
46. Fifis T, Gamvrellis A, Crimeen-Irwin B, Pietersz GA, Li J, Mottram PL, et al. Size-dependent immunogenicity: Therapeutic and protective properties of nano-vaccines against tumors. J Immunol. 2004;173(5):3148-54. [Link] [DOI:10.4049/jimmunol.173.5.3148]
47. Gutierro I, Hernández RM, Igartua M, Gascón AR, Pedraz JL. Size dependent immune response after subcutaneous, oral and intranasal administration of BSA loaded nanospheres. Vaccine. 2002;21(1-2):67-77. [Link] [DOI:10.1016/S0264-410X(02)00435-8]
48. Dobrovolskaia MA, Aggarwal P, Hall JB, McNeil SE. Preclinical studies to understand nanoparticle interaction with the immune system and its potential effects on nanoparticle biodistribution. Mol Pharm. 2008;5(4):487-95. [Link] [DOI:10.1021/mp800032f]
49. Cho WS, Dart K, Nowakowska DJ, Zheng X, Donaldson K, Howie SE. Adjuvanticity and toxicity of cobalt oxide nanoparticles as an alternative vaccine adjuvant. Nanomedicine. 2012;7(10):1495-505. [Link] [DOI:10.2217/nnm.12.35]
50. Castignolles N, Morgeaux S, Gontier-Jallet C, Samain D, Betbeder D, Perrin P. A new family of carriers (biovectors) enhances the immunogenicity of Rabies antigens. Vaccine. 1996;14(14):1353-60. [Link] [DOI:10.1016/S0264-410X(96)00043-6]
51. Dykman LA, Sumaroka MV, Staroverov SA, Zaĭtseva IS, Bogatyrev VA. Immunogenic properties of colloidal Gold. Biol Bull Russ Acad Sci. 2004;31(1):75-9. [Link] [DOI:10.1023/B:BIBU.0000014358.98422.9c]
52. Scheerlinck JP, Gloster S, Gamvrellis A, Mottram PL, Plebanski M. Systemic immune responses in sheep, induced by a novel nano-bead adjuvant. Vaccine. 2006;24(8):1124-31. [Link] [DOI:10.1016/j.vaccine.2005.09.009]
53. Greenwood DL, Dynon K, Kalkanidis M, Xiang S, Plebanski M, Scheerlinck JP. Vaccination against foot-and-mouth disease virus using peptides conjugated to nano-beads. Vaccine. 2008;26(22):2706-13. [Link] [DOI:10.1016/j.vaccine.2008.03.025]
54. Peyre M, Sesardic D, Merkle HP, Gander B, Johansen P. An experimental divalent vaccine based on biodegradable microspheres induces protective immunity against Tetanus and Diphtheria. J Pharm Sci. 2003;92(5):957-66. [Link] [DOI:10.1002/jps.10361]
55. Nayak B, Panda AK, Ray P, Ray AR. Formulation, characterization and evaluation of rotavirus encapsulated PLA and PLGA particles for oral vaccination. J Microencapsul. 2009;26(2):154-65. [Link] [DOI:10.1080/02652040802211709]
56. Cheng J, Teply BA, Sherifi I, Sung J, Luther G, Gu FX, et al. Formulation of functionalized PLGA-PEG nanoparticles for in vivo targeted drug delivery. Biomaterials. 2007;28(5):869-76. [Link] [DOI:10.1016/j.biomaterials.2006.09.047]
57. Bharali DJ, Mousa SA, Thanavala Y. Micro- and nanoparticle-based vaccines for hepatitis B. In: Shurin MR, Smolkin YS, editors. Immune-mediated diseases: From theory to therapy. Berlin: Springer Science & Business Media; 2007. pp. 415-21. [Link] [DOI:10.1007/978-0-387-72005-0_44]
58. Diwan M, Elamanchili P, Lane H, Gainer A, Samuel J. Biodegradable nanoparticle mediated antigen delivery to human cord blood derived dendritic cells for induction of primary T cell responses. J Drug Target. 2003;11(8-10):495-507. [Link] [DOI:10.1080/10611860410001670026]
59. Storni T, Kündig TM, Senti G, Johansen P. Immunity in response to particulate antigen-delivery systems. Adv Drug Deliv Rev. 2005;57(3):333-55. [Link] [DOI:10.1016/j.addr.2004.09.008]
60. Sun H, Pollock KG, Brewer JM. Analysis of the role of vaccine adjuvants in modulating dendritic cell activation and antigen presentation in vitro. Vaccine. 2003;21(9-10):849-55. [Link] [DOI:10.1016/S0264-410X(02)00531-5]
61. Igartua M, Hernández RM, Rosas JE, Patarroyo ME, Pedraz JL. Gamma-irradiation effects on biopharmaceutical properties of PLGA microspheres loaded with SPf66 synthetic vaccine. Eur J Pharm Biopharm. 2008;69(2):519-26. [Link] [DOI:10.1016/j.ejpb.2007.12.014]

Add your comments about this article : Your username or Email:

Send email to the article author