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Preparation and Characterization of Chitosan-coated PLGA Nanoparticle

키토산이 코팅된 PLGA 나노입자의 제조 및 특성

  • Yu, Su-Gyeong (Department of Polymer Science and Engineering, Sunchon National University) ;
  • Nah, Jae-Woon (Department of Polymer Science and Engineering, Sunchon National University) ;
  • Jeong, Gyeong-Won (Department of Bioenvironmental & Chemical Engineering, Chosun College of Science and Technology)
  • 유수경 (순천대학교 공과대학 고분자공학과) ;
  • 나재운 (순천대학교 공과대학 고분자공학과) ;
  • 정경원 (조선이공대학교 생명환경화공과)
  • Received : 2021.07.05
  • Accepted : 2021.08.02
  • Published : 2021.10.10

Abstract

In this study, poly lactic-co-glycolic acid (PLGA) nanoparticles (PNP) were prepared through double (w/o/w) emlusion and emulsifying solvent-evaporation technique using PLGA, which has biocompatibility and biodegradability. To maximize stability and bioavailability of the particles, chitosan-coated PLGA nanoparticles (CPNP) were prepared by charge interaction between PNP and chitosan. We demonstrated that CPNP can be utilized as a drug carrier of oral administration. The chemical structure of CPNP was analyzed by 1H-NMR and FT-IR, and all characteristic peaks appeared, confirming that it was successfully prepared. In addition, particle size and zeta potential of CPNP were analyzed using dynamic light scattering (DLS) while morphological images were obtained using transmission electron microscope (TEM). Thermal decomposition behavior of CPNP was observed through thermogravimetric analysis (TGA). In addition, the cytotoxicity of CPNP was confirmed by MTT assay at HEK293 and L929 cell lines, and it was proved that there is no toxicity confirmed by the cell viability of above 70% at all concentrations. These results suggest that the CPNP developed in this study may be used as an oral drug delivery carrier.

본 연구는 생체적합성 및 생분해성의 특성을 갖는 PLGA (poly lactic-co-glycolic acid)를 이용하여 이중(w/o/w) emlusion과 유화 용매-증발 기법을 통해 PLGA 나노입자(PNP)를 제조하였고, 이에 키토산을 전하 상호작용을 통해 키토산이 코팅된 PLGA 나노입자(CPNP)를 제조하여 입자의 안정성과 생체이용률을 극대화할 수 있는 경구 투여용 약물 전달체로 사용 가능성을 입증하고자 하였다. CPNP의 화학적 구조는 1H-NMR 및 FT-IR을 통해 분석하였으며, 모든 특성 피크가 나타남으로써 성공적으로 제조되었음을 확인하였다. 또한, CPNP의 입자 크기, 제타 전위 및 형태학적 이미지는 DLS와 TEM을 이용하여 각각 분석하였으며, TGA를 통해 CPNP의 열적 분해 거동을 관찰하였다. 또한, CPNP의 세포 독성은 HEK293 및 L929 세포에서 MTT assay를 수행하여 확인하였고, 모든 농도에서 70% 이상의 세포 생존율을 확인함으로써 독성이 없음을 입증하였다. 이러한 결과를 통해 본 연구에서 개발된 CPNP가 경구용 약물 전달체로써 사용 가능성이 있음을 제안한다.

Keywords

References

  1. P. Colucci, C. S. Yue, M. Ducharme, S. Benvenga, A review of the pharmacokinetics of levothyroxine for the treatment of hypothyroidism, Eur. Endocrinol., 9, 40 (2013).
  2. M. Goldberg, I. Gomez-Orellana, Challenges for the oral delivery of macromolecules, Nat. Rev. Drug Discov., 2, 289-295 (2003). https://doi.org/10.1038/nrd1067
  3. R. Duncan, H. Ringsdorf, R. Satchi-Fainaro, Polymer therapeutics-polymers as drugs, drug and protein conjugates and gene delivery systems: past, present and future opportunities, J. Drug Target., 14, 337-341 (2006). https://doi.org/10.1080/10611860600833856
  4. E. W. Ng, D. T. Shima, P. Calias, E.T . Cunningham, D.R. Guyer, A.P. Adamis, Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease, Nat. Rev. Drug Discov., 5, 123-132 (2006). https://doi.org/10.1038/nrd1955
  5. Y. Yun, Y. W. Cho, K. Park, Nanoparticles for oral delivery: targeted nanoparticles with peptidic ligands for oral protein delivery, Adv. Drug Deliv. Rev., 65, 822-832 (2013). https://doi.org/10.1016/j.addr.2012.10.007
  6. N. Krinick, Y. Sun, D. Joyner, J. Spikes, R. Straight, J. Kopecek, A polymeric drug delivery system for the simultaneous delivery of drugs activatable by enzymes and/or light, J. Biomater. Sci., 5, 303-324 (1994). https://doi.org/10.1163/156856294X00040
  7. M. A. Moses, H. Brem, R. Langer, Advancing the field of drug delivery: taking aim at cancer, Cancer Cell, 4, 337-341 (2003). https://doi.org/10.1016/S1535-6108(03)00276-9
  8. S. A. Vinores, Pegaptanib in the treatment of wet, age-related macular degeneration, Int. J. Nanomedicine, 1, 263 (2006).
  9. E. Chiellini, R. Solaro, Biodegradable polymeric materials, Adv. Mater., 8, 305-313 (1996). https://doi.org/10.1002/adma.19960080406
  10. C. S. Brazel, S. L. Rosen, Fundamental principles of polymeric materials, John Wiley & Sons (2012).
  11. S. A. Wickline, A. M. Neubauer, P. M. Winter, S. D. Caruthers, G. M. Lanza, Molecular imaging and therapy of atherosclerosis with targeted nanoparticles, J. Magn. Reson. Imaging, 25, 667-680 (2007). https://doi.org/10.1002/jmri.20866
  12. X. Zhang, M. Sun, A. Zheng, D. Cao, Y. Bi, J. Sun, Preparation and characterization of insulin-loaded bioadhesive PLGA nanoparticles for oral administration, Eur. J. Pharm. Sci., 45, 632-638 (2012). https://doi.org/10.1016/j.ejps.2012.01.002
  13. E. Locatelli, M. C. Franchini, Biodegradable PLGA-b-PEG polymeric nanoparticles: synthesis, properties, and nanomedical applications as drug delivery system, J. Nanoparticle Res., 14, 1316 (2012). https://doi.org/10.1007/s11051-012-1316-4
  14. M. M. Badran, A. H. Alomrani, G. I. Harisa, A. E. Ashour, A. Kumar, A. E. Yassin, Novel docetaxel chitosan-coated PLGA/PCL nanoparticles with magnified cytotoxicity and bioavailability, Biomed. Pharmacother., 106, 1461-1468 (2018). https://doi.org/10.1016/j.biopha.2018.07.102
  15. D. Ding, Q. Zhu, Recent advances of PLGA micro/nanoparticles for the delivery of biomacromolecular therapeutics, Mater. Sci. Eng., C, 92, 1041-1060 (2018). https://doi.org/10.1016/j.msec.2017.12.036
  16. N. K. Al-Nemrawi, A. R. Okour, R. H. Dave, Surface modification of PLGA nanoparticles using chitosan: Effect of molecular weight, concentration, and degree of deacetylation, Adv. Polym. Technol., 37, 3066-3075 (2018). https://doi.org/10.1002/adv.22077
  17. L. Hu, X. Meng, R. Xing, S. Liu, X. Chen, Y. Qin, H. Yu, P. Li, Design, synthesis and antimicrobial activity of 6-N-substituted chitosan derivatives, Bioorg. Med. Chem. Lett., 26, 4548-4551 (2016). https://doi.org/10.1016/j.bmcl.2015.08.047
  18. A. Zimoch-Korzycka, L. Bobak, A. Jarmoluk, Antimicrobial and antioxidant activity of chitosan/hydroxypropyl methylcellulose film-forming hydrosols hydrolyzed by cellulase, Int. J. Mol. Sci., 17, 1436 (2016). https://doi.org/10.3390/ijms17091436
  19. G.-W. Jeong, S.-C. Park, C. Choi, J.-P. Nam, T.-H. Kim, S.-K. Choi, J.-K. Park, J.-W. Nah, Anticancer effect of gene/peptide co-delivery system using transferrin-grafted LMWSC, Int. J. Pharm., 488, 165-173 (2015). https://doi.org/10.1016/j.ijpharm.2015.04.057
  20. M. P. Patel, R. R. Patel, J. K. Patel, Chitosan mediated targeted drug delivery system: a review, J. Pharm. Pharm., 13, 536-557 (2010). https://doi.org/10.1111/j.2042-7158.1961.tb11866.x
  21. B. Semete, L. Booysen, L. Kalombo, J. D. Venter, L. Katata, B. Ramalapa, J. A. Verschoor, H. Swai, In vivo uptake and acute immune response to orally administered chitosan and PEG coated PLGA nanoparticles, Toxicol. Appl. Pharmacol., 249, 158-165 (2010). https://doi.org/10.1016/j.taap.2010.09.002