Combined effects of PEGylation and particle size on uptake of PLGA particles by macrophage cells

Document Type : Research Paper

Authors

1 School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

3 Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran

4 Nanotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective:
At the present study, relationship between phagocytosis of PLGA particles and combined effects of particle size and surface PEGylation was investigated. 
Materials and Methods:
Microspheres and nanospheres (3500 nm and 700 nm) were prepared from three types of PLGA polymers (non-PEGylated and PEGylation percents of 9% and 15%). These particles were prepared by solvent evaporation method. All particles were labeled with FITC-Albumin. Interaction of particles with J744.A.1 mouse macrophage cells, was evaluated in the absence or presence of 7% of the serum by flowcytometry method. 
Results:  
The study revealed more phagocytosis of nanospheres. In the presence of the serum, PEGylated particles were phagocytosed less than non-PEGylated particles. For nanospheres, this difference was significant (P<0/05) and their uptake was affected by PEGylation degree. In the case of microsphere formulation, PEGylation did not affect the cell uptake. In the serum-free medium, the bigger particles had more cell uptake rate than smaller ones but the cell uptake rate was not influenced by PEGylation. 
Conclusion:
The results indicated that in nanosized particles both size and PEgylation degree could affect the phagocytosis, but in micron sized particles just size, and not the PEGylation degree, could affect this.

Keywords


1. Poovi G, Lekshmi UMD, Narayanan N, Reddy N. Preparation and characterization of repaglinide loaded chitosan polymeric nanoparticles. Res J Nanosci Nanotechnol. 2011; 1(1): 12-24.
2. Khameneh B, Iranshahy M, Ghandadi M, Ghoochi Atashbeyk D, Fazly Bazzaz BS, Iranshahi M. Investigation of the antibacterial activity and efflux pump inhibitory effect of co-loaded piperine and gentamicin nanoliposomes in methicillin-resistant Staphylococcus aureus. Drug Dev Ind Pharm. 2014 May 20.
3. Atashbeyk DG, Khameneh B, Tafaghodi M, Fazly Bazzaz BS. Eradication of methicillin-resistant Staphylococcus aureus infection by nanoliposomes loaded with gentamicin and oleic acid. Pharm Biol. 2014 Nov; 52(11): 1423-8.
4. Mohajer M, Khameneh B, Tafaghodi M. Preparation and characterization of PLGA nanospheres loaded with inactivated influenza virus, CpG-ODN and Quillaja saponin. Iran J Basic Med Sci. 2014 Sep; 17(9): 722-6.
5. Ding X, Janjanam J, Tiwari A, Thompson M, Heiden PA. Peptide-directed self-assembly of functionalized polymeric nanoparticles part I: design and self-assembly of peptide-copolymer conjugates into nanoparticle fibers and 3D scaffolds. Macromol Biosci. 2014 Jun; 14(6): 853-71.
6. Yao H, Ng SS, Huo LF, Chow BK, Shen Z, Yang M, et al. Effective melanoma immunotherapy with interleukin-2 delivered by a novel polymeric nanoparticle. Mol Cancer Ther. 2011 Jun;10(6): 1082-92.
7. Sun L, Zhou S, Wang W, Li X, Wang J, Weng J. Preparation and characterization of porous biodegradable microspheres used for controlled protein delivery. Colloids Surf A Physicochem Eng Asp. 2009;345(1–3):173-81.
8. Bian X, Liang S, John J, Hsiao CH, Wei X, Liang D, et al. Development of PLGA-based itraconazole injectable nanospheres for sustained release. Int J Nanomedicine. 2013; 8: 4521-31.
9. Gajendiran M, Divakar S, Raaman N, Balasubramanian S. In vitro drug release behavior, mechanism and antimicrobial activity of rifampicin loaded low molecular weight PLGA-PEG-PLGA triblock copolymeric nanospheres. Curr Drug Deliv. 2013 Dec; 10(6): 722-31.
10. Mohaghegh M, Tafaghodi M. Dextran microspheres could enhance immune responses against PLGA nanospheres encapsulated with tetanus toxoid and Quillaja saponins after nasal immunization in rabbit. Pharm Dev Technol. 2011 Feb; 16(1): 36-43.
11. Jain RA. The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. Biomaterials. 2000; 21(23): 2475-90.
12. Misra R, Acharya S, Sahoo SK. Cancer nanotechnology: Application of nanotechnology in cancer therapy. Drug Discov Today. 2010; 15(19-20): 842-50.
13. Nijhara R, Balakrishnan K. Bringing nanomedicines to market: regulatory challenges, opportunities, and uncertainties. Nanomedicine: Nanotechnology, Biology, and Medicine. 2006; 2(2): 127-36.
14. Moghimi SM, Hunter AC, Murray JC. Long-circulating and target-specific nanoparticles: Theory to practice. Pharmacol Rev. 2001; 53(2): 283-318.
15. Hans ML, Lowman AM. Biodegradable nanoparticles for drug delivery and targeting. Curr Opin Solid State Mater Sci. 2002; 6(4): 319-27.
16. Mosqueira VCF, Legrand P, Gref R, Heurtault B, Appel M, Barratt G. Interactions between a macrophage cell line (J774A1) and surface-modified Poly(D,L-lactide) nanocapsules bearing poly(ethylene glycol). J Drug Target. 1999; 7(1): 65-78.
17. Thiele L, Diederichs JE, Reszka R, Merkle HP, Walter E. Competitive adsorption of serum proteins at microparticles affects phagocytosis by dendritic cells. Biomaterials. 2003; 24(8): 1409-18.
18. Kohler N, Sun C, Fichtenholtz A, Gunn J, Fang C, Zhang M. Methotrexate-immobilized poly(ethylene glycol) magnetic nanoparticles for MR imaging and drug delivery. Small. 2006; 2(6): 785-92.
19. Chaudhari KR, Ukawala M, Manjappa AS, Kumar A, Mundada PK, Mishra AK, et al. Opsonization, biodistribution, cellular uptake and apoptosis study of PEGylated PBCA nanoparticle as potential drug delivery carrier. Pharm Res. 2012 Jan;29(1):53-68.
20. Mathaes R, Winter G, Besheer A, Engert J. Influence of particle geometry and PEGylation on phagocytosis of particulate carriers. Int J Pharm. 2014; 465(1-2): 159-64.
21. Champion JA, Walker A, Mitragotri S. Role of particle size in phagocytosis of polymeric microspheres. Pharm Res. 2008 Aug; 25(8): 1815-21.
22. Tafaghodi M, Hadizadeh F, Farahmand F. Determination of encapsulation efficiency of tetanus toxoid in microsphere and liposome drug delivery systems by two different spectroscopic methods. Pharmaceutical Sciences. 2008; 2: 53-9.
23. 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. 2002; 82(1): 105-14.
24. Ahsan F, Rivas IP, Khan MA, Torres Suárez AI. Targeting to macrophages: role of physicochemical properties of particulate carriers—liposomes and microspheres—on the phagocytosis by macrophages. J Control Release. 2002; 79(1): 29-40.
25. Owens Iii DE, Peppas NA. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm. 2006 ;307(1): 93-102.
26. Zambaux M-F, Faivre-Fiorina B, Bonneaux F, Marchal S, Merlin J-L, Dellacherie E, et al. Involvement of neutrophilic granulocytes in the uptake of biodegradable non-stealth and stealth nanoparticles in guinea pig. Biomaterials. 2000; 21(10): 975-80.
27. Leroux JC, De Jaeghere F, Anner B, Doelker E, Gurny R. An investigation on the role of plasma and serum opsonins on the internalization of biodegradable poly(D,L-lactic acid) nanoparticles by human monocytes. Life Sciences. 1995; 57(7): 695-703.
28. Tabata Y, Ikada Y. Effect of the size and surface charge of polymer microspheres on their phagocytosis by macrophage. Biomaterials. 1988; 9(4): 356-62.
29. Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE. Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release. 2001 Jan 29; 70(1-2): 1-20.
30. Owens DE, 3rd, Peppas NA. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm. 2006 Jan 3; 307(1): 93-102.