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http://dx.doi.org/10.4110/in.2011.11.3.163

Formulation and Characterization of Antigen-loaded PLGA Nanoparticles for Efficient Cross-priming of the Antigen  

Lee, Young-Ran (College of Pharmacy, Chungbuk National University)
Lee, Young-Hee (College of Pharmacy, Chungbuk National University)
Im, Sun-A (College of Pharmacy, Chungbuk National University)
Kim, Kyung-Jae (College of Pharmacy, ShamYook University)
Lee, Chong-Kil (College of Pharmacy, Chungbuk National University)
Publication Information
IMMUNE NETWORK / v.11, no.3, 2011 , pp. 163-168 More about this Journal
Abstract
Background: Nanoparticles (NPs) prepared from biodegradable polymers, such as poly (D,L-lactic acid-co-glycolic acid) (PLGA), have been studied as vehicles for the delivery of antigens to phagocytes. This paper describes the preparation of antigen-loaded PLGA-NPs for efficient cross-priming. Methods: NPs containing a similar amount of ovalbumin (OVA) but different sizes were produced using a micromixer-based W/O/W solvent evaporation procedure, and the efficiency of the NPs to induce the cross-presentation of OVA peptides were examined in dendritic cells (DCs). Cellular uptake and biodistribution studies were performed using fluorescein isothiocyanate (FITC)-loaded NPs in mice. Results: The NPs in the range of $1.1{\sim}1.4{\mu}m$ in size were the most and almost equally efficient in inducing the cross-presentation of OVA peptides via $H-2K^b$ molecules. Cellular uptake and biodistribution studies showed that opsonization of the NPs with mouse IgG greatly increased the percentage of FITC-positive cells in the spleen and lymph nodes. The major cell type of FITC-positive cells in the spleen was macrophages, whereas that of lymph nodes was DCs. Conclusion: These results show that IgG-opsonized PLGA-NPs with a mean size of $1.1{\mu}m$ would be the choice of biodegradable carriers for the targeted-delivery of protein antigens for cross-priming in vivo.
Keywords
PLGA; Nanoparticle; Opsonization; Cross-priming;
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1 Bevan MJ: Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not cross-react in the cytotoxic assay. J Exp Med 143;1283-1288, 1976   DOI   ScienceOn
2 Elamanchili P, Diwan M, Cao M, Samuel J: Characterization of poly(D,L-lactic-co-glycolic acid) based nanoparticulate system for enhanced delivery of antigens to dendritic cells. Vaccine 22;2406-2412, 2004   DOI   ScienceOn
3 Champion JA, Walker A, Mitragotri S: Role of particle size in phagocytosis of polymeric microspheres. Pharm Res 25;1815-1821, 2008   DOI   ScienceOn
4 Huang AY, Golumbek P, Ahmadzadeh M, Jaffee E, Pardoll D, Levitsky H: Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science 264;961-965, 1994   DOI
5 Gerelchuluun T, Lee YH, Lee YR, Im SA, Song S, Park JS, Han K, Kim K, Lee CK: Dendritic cells process antigens encapsulated in a biodegradable polymer, poly(D,L-lactide- co-glycolide), via an alternate class I MHC processing pathway. Arch Pharm Res 30;1440-1446, 2007   DOI
6 Harding CV, Song R: Phagocytic processing of exogenous particulate antigens by macrophages for presentation by class I MHC molecules. J Immunol 153;4925-4933, 1994
7 Heath WR, Carbone FR: Cross-presentation, dendritic cells, tolerance and immunity. Annu Rev Immunol 19;47-64, 2001   DOI   ScienceOn
8 Jiang W, Gupta RK, Deshpande MC, Schwendeman SP: Biodegradable poly(lactic-co-glycolic acid) microparticles for injectable delivery of vaccine antigens. Adv Drug Deliv Rev 57;391-410, 2005   DOI   ScienceOn
9 Johansen P, Men Y, Merkle HP, Gander B: Revisiting PLA/PLGA microspheres: an analysis of their potential in parenteral vaccination. Eur J Pharm Biopharm 50;129-146, 2000   DOI   ScienceOn
10 Karttunen J, Sanderson S, Shastri N: Detection of rare antigen- presenting cells by the lacZ T-cell activation assay suggests an expression cloning strategy for T-cell antigens. Proc Natl Acad Sci U S A 89;6020-6024, 1992   DOI   ScienceOn
11 Kocbek P, Obermajer N, Cegnar M, Kos J, Kristl J: Targeting cancer cells using PLGA nanoparticles surface modified with monoclonal antibody. J Control Release 120;18-26, 2007   DOI
12 Lee JK, Lee MK, Yun YP, Kim Y, Kim JS, Kim YS, Kim K, Han SS, Lee CK: Acemannan purified from Aloe vera induces phenotypic and functional maturation of immature dendritic cells. Int Immunopharmacol 1;1275-1284, 2001   DOI   ScienceOn
13 Sigal LJ, Crotty S, Andino R, Rock KL: Cytotoxic T-cell immunity to virus-infected non-haematopoietic cells requires presentation of exogenous antigen. Nature 398;77-80, 1999   DOI
14 Lee YH, Lee YR, Kim KH, Im SA, Song S, Lee MK, Kim Y, Hong JT, Kim K, Lee CK: Baccatin III, a synthetic precursor of taxol, enhances MHC-restricted antigen presentation in dendritic cells. Int Immunopharmacol 2011 [Epub ahead of print]
15 Lee YR, Yang IH, Lee YH, Im SA, Song S, Li H, Han K, Kim K, Eo SK, Lee CK: Cyclosporin A and tacrolimus, but not rapamycin, inhibit MHC-restricted antigen presentation pathways in dendritic cells. Blood 105;3951-3955, 2005   DOI   ScienceOn
16 Mundargi RC, Babu VR, Rangaswamy V, Patel P, Aminabhavi TM: Nano/micro technologies for delivering macromolecular therapeutics using poly(D,L-lactide-co-glycolide) and its derivatives. J Control Release 125;193-209, 2008   DOI   ScienceOn
17 Sahoo SK, Panyam J, Prabha S, Labhasetwar V: Residual polyvinyl alcohol associated with poly (D,L-lactide-co-glycolide) nanoparticles affects their physical properties and cellular uptake. J Control Release 82;105-114, 2002   DOI   ScienceOn
18 Shen H, Ackerman AL, Cody V, Giodini A, Hinson ER, Cresswell P, Edelson RL, Saltzman WM, Hanlon DJ: Enhanced and prolonged cross-presentation following endosomal escape of exogenous antigens encapsulated in biodegradable nanoparticles. Immunology 117;78-88, 2006   DOI   ScienceOn
19 Venkataprasad N, Coombes AG, Singh M, Rohde M, Wilkinson K, Hudecz F, Davis SS, Vordermeier HM: Induction of cellular immunity to a mycobacterial antigen adsorbed on lamellar particles of lactide polymers. Vaccine 17;1814-1819, 1999   DOI   ScienceOn
20 Waeckerle-Men Y, Groettrup M: PLGA microspheres for improved antigen delivery to dendritic cells as cellular vaccines. Adv Drug Deliv Rev 57;475-482, 2005   DOI   ScienceOn
21 Yewdell JW, Haeryfar SM: Understanding presentation of viral antigens to CD8+ T cells in vivo: the key to rational vaccine design. Annu Rev Immunol 23;651-682, 2005   DOI   ScienceOn
22 Panyam J, Labhasetwar V: Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev 55;329-347, 2003   DOI   ScienceOn
23 Newman KD, Sosnowski DL, Kwon GS, Samuel J: Delivery of MUC1 mucin peptide by Poly(d,l-lactic-co-glycolic acid) microspheres induces type 1 T helper immune responses. J Pharm Sci 87;1421-1427, 1998   DOI