키토산이 코팅된 PLGA 나노입자의 제조 및 특성

유수경; 나재운; 정경원; Su-Gyeong Yu; Jae-Woon Nah; Gyeong-Won Jeong

Applied Chemistry for Engineering, Vol.32, No.5, 509-515, October, 2021

DOI10.14478/ace.2021.1058 Export Citation

키토산이 코팅된 PLGA 나노입자의 제조 및 특성

Preparation and Characterization of Chitosan-coated PLGA Nanoparticle

유수경, 나재운 ^†, 정경원^{1, †}

순천대학교 공과대학 고분자공학과
¹조선이공대학교 생명환경화공과

Su-Gyeong Yu, Jae-Woon Nah^†, and Gyeong-Won Jeong^{1, †}

Department of Polymer Science and Engineering, Sunchon National University, Jeonnam 57922, Republic of Korea
¹Department of Bioenvironmental & Chemical Engineering, Chosun College of Science and Technology, Gwangju 61453, Republic of Korea

E-mail:,

초록

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 세포독성은 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.

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.

Keywords:Chitosan;PLGA;Oral delivery carrier;Stability;Bioavailability

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[1] Colucci P, Yue CS, Ducharme M, Benvenga S, Eur. Endocrinol., 9, 40 (2013)

[2] Goldberg M, Gomez-Orellana I, Nat. Rev. Drug Discov., 2, 289 (2003)

[3] Duncan R, Ringsdorf H, Satchi-Fainaro R, J. Drug Target., 14, 337 (2006)

[4] Ng EW, Shima DT, Calias P, Cunningham ET, Guyer DR, Adamis AP, Nat. Rev. Drug Discov., 5, 123 (2006)

[5] Yun Y, Cho YW, Park K, Adv. Drug Deliv. Rev., 65, 822 (2013)

[6] Krinick N, Sun Y, Joyner D, Spikes J, Straight R, Kopecek J, J. Biomater. Sci., 5, 303 (1994)

[7] Moses MA, Brem H, Langer R, Cancer Cell, 4, 337 (2003)

[8] Vinores SA, Int. J. Nanomedicine, 1, 263 (2006)

[9] Chiellini E, Solaro R, Adv. Mater., 8(4), 305 (1996)

[10] Brazel CS, Rosen SL, Fundamental principles of polymeric materials, John Wiley & Sons (2012).

[11] Wickline SA, Neubauer AM, Winter PM, Caruthers SD, Lanza GM, J. Magn. Reson. Imaging, 25, 667 (2007)

[12] Zhang X, Sun M, Zheng A, Cao D, Bi Y, Sun J, Eur. J. Pharm. Sci., 45, 632 (2012)

[13] Locatelli E, Franchini MC, J. Nanoparticle Res., 14, 1316 (2012)

[14] Badran MM, Alomrani AH, Harisa GI, Ashour AE, Kumar A, Yassin AE, Biomed. Pharmacother., 106, 1461 (2018)

[15] Ding D, Zhu Q, Mater. Sci. Eng. C-Biomimetic Supramol. Syst., 92, 1041 (2018)

[16] Al.Nemrawi NK, Okour AR, Dave RH, Adv. Polym. Technol., 37, 3066 (2018)

[17] Hu L, Meng X, Xing R, Liu S, Chen X, Qin Y, Yu H, Li P, Bioorg. Med. Chem. Lett., 26, 4548 (2016)

[18] Zimoch-Korzycka A, Bobak L, Jarmoluk A, Int. J. Mol. Sci., 17, 1436 (2016)

[19] Jeong GW, Park SC, Choi C, Nam JP, Kim TH, Choi SK, Park JK, Nah JW, Int. J. Pharm., 488, 165 (2015)

[20] Patel MP, Patel RR, Patel JK, J. Pharm. Pharmacol., 13, 536 (2010)

[21] Semete B, Booysen L, Kalombo L, Venter JD, Katata L, Ramalapa B, Verschoor JA, Swai H, Toxicol. Appl. Pharmacol., 249, 158 (2010)