Abstract：OBJECTIVE To prepare chitosan oligosaccharide nanoparticles loaded with baicalin, optimize the preparation process, and study the inhibitory effect on MCF-7 breast cancer cells. METHODS Nanoparticles were prepared by the method of ionic cross-linking with baicalin as model drug. Based on results from the single factor tests, orthogonal experimental design method was used to investigate the factors influence on encapsulation rate of nanoparticels. The cytotoxicity of drug-loaded nanoparticles to MCF-7 cells in vitro were also investigated by CCK8 assay. RESULTS The optimum conditions for the preparation of baicalin-chitosan oligosaccharide- nanoparticels were: pH of chitosan oligosaccharide solution was 4, baicalin dosage was 1.4 mg, the dosage of chitosan oligosaccharide was 140 mg, the dosage of sodium tripolyphosphate was 4 mg, and the stirring time was 10 min.The mean diameter was(63.2±2.7)nm, encapsulation rate(82.87±1.54)% and the drug loading(6.01±0.24)%. TEM photos showed that nanoparticles were spherical or quasi-spherical, with relatively complete morphology and uniform distribution. In vitro cell inhibition experiments indicated that baicalin-chitosan oligosaccharide-nanoparticles showed stronger inhibition against MCF-7 cells. With the increase of concentration and time, the inhibitory rate of baicalin-chitosan oligosaccharide-nanoparticles on MCF-7 cells showed significant difference compared with baicalin(P<0.05). CONCLUSION The particle size of baicalin-chitosan oligosaccharide-nanoparticles prepared by this method is small, and it had better inhibitory effect on MCF-7 breast cancer cells.
吕凤娇, 蔡菊虹, 宋婧雯, 孙丽丹, 谢晓兰. 黄芩苷壳寡糖纳米粒的制备及其对MCF-7乳腺癌细胞的抑制作用研究[J]. 中国药学杂志, 2023, 58(8): 708-716.
Lü Feng-jiao, CAI Ju-hong, SONG Jing-wen, SUN Li-dan, XIE Xiao-lan. Preparation of Baicalin-Chitosan Oligosaccharide-Nanoparticles and Its Inhibitory Effect on MCF-7 Breast Cancer Cells. Chinese Pharmaceutical Journal, 2023, 58(8): 708-716.
ZHOU M H, ZHANG M, ZHANG S, et al. Effect of molecular weight of polyethylene glycol on pharmaco- kinetics of baicalin. Acta Pharm Sin(药学学报), 2021, 56(5):1416- 1423.
[2]
XU Q, OU Y Y, WU H F. Absorption Mechanism of Baicalin and its Solid Lipid Nanoparticles on Caco-2 Cells. Chin Pharm J(中国药学杂志), 2019, 54(12): 1000-1006.
[3]
LEE D, KO W K, HWANG D S, et al. Use of Baicalin- Conjugated Gold Nanoparticles for Apoptotic Induction of Breast Cancer Cells. Nanoscale Res Lett, 2016, 11(1):381-381.
[4]
WANG N, TANG L J, ZHU G Q, et al. Apoptosis induced by baicalin involving up-regulation of P53 and bax in MCF-7 cells. J Asian Nat Prod Res, 2008, 10(12):1129-1135.
[5]
CHEN Y, WANG K, ZHANG L L. Research progress of liposomes coated with chitosan for drug delivery. Chin J Mod Appl Pharm(中国现代应用药学), 2021, 38(10):1251-1256.
[6]
WANG Y J, JIANG X Y, LEI Y, et al. Preparations and evaluations of in vitro and in vivo characteristics . Chin J Hosp Pharm(中国医院药学杂志), 2021, 40(10):1005-1012.
[7]
REN Z K, GAO W, LIU C, et al. Preparation of naringenin chitosan nanoparticle and its cellular evaluation in vitro. Chin Pharm J(中国药学杂志), 2017, 37(20):2056-2060.
[8]
HE J Y, WU L, WANG J C, et al. Anti-tumor effect of brucine-loaded chitosan nanoparticles in vitro. Acta Pharm Sin(药学学报), 2016, 51(4):650-656.
[9]
ZU Y G, ZHAO Q, ZHAO X H, et al. Process optimization for the preparation of oligomycin-loaded folate-conjugated chitosan nanoparticles as a tumor-targeted drug delivery system using a two-level factorial design method. Int J Nanomed, 2012, 6:3429-3441.
[10]
HAO Y K, YANG X D.Research progress of drug- carrying chitosan nanoparticles. Chin Pharm J(中国药学杂志), 2005, 40(17):1292- 1295.
[11]
LIU H, JIANG J Y, WANG L L, et al. Preparation of doxorubicin-loaded chitosan oligosaccharide nano- particles and its anti-tumor effect in vitro. Chin J Biochem Pharm(中国生化药物杂志), 2015, 35(1):25-29.
[12]
WEI X H, NIU Y P, XU Y Y, et al.Salicylic acid-grafted chitosan oligosaccharide nanoparticle for paclitaxel delivery. J Bioactive Compatible Polymers, 2010, 25(3):319-335.
[13]
UBONVAN T, HYUN JC, DONG HW, et al. Chitosan oligosaccharide-arachidic acid-based nanopartocles for anti-cancer drug delivery. Int J Pharm, 2013, 441(1-2):373-380.
[14]
LIU Z J, LI X C, ZHAO M F, et al. Preparation and evaluation of hydroxy-loaded camptothecin nanoparticles in vitro. Chin J Hosp Pharm(中国医院药学杂志), 2015, 35(21):1910-1914.
[15]
CAO J, ZHOU N J. Progess in antitumor studies of chitosan. Chin J Biochem Pharm(中国生化药物杂志), 2005, 26(2):126-127.
[16]
XU X Y, SUN L P, ZHOU L, et al. Functional chitosan oligosaccharide nanomicelles for topical ocular drug delivery of dexamethasone. Carbohydr Polym, 2020, 227:115356. Doi:10.1016/j.carbpol.2019.115356.
[17]
WANG Y, KHAN A, LIU Y, et al. Chitosan oligosaccharide-based dual pH responsive nano-micelles for targeted delivery of hydrophobic drugs. Carbohydr polym, 2019, 223: 115061. Doi:10.1016/j.carbpol.2019.115061.
[18]
YI G, LING J H, JIANG Y J, et al. Fabrication, characterization, and in vitro evaluation of doxorubicin-coupled chitosan oligosaccharide nanoparticles. J Mol Struct, 2022, 1268: 133688. Doi:10.1016/j.molstruc.2022.133688.
[19]
LI R W, LYU Y, LUO S M, et al. Fabrication of a multi-level drug release platform with liposomes, chitooligosaccharides, phospholipids and injectable chitosan hydrogel to enhance anti-tumor effectiveness. Carbohydr Polym, 2021, 269: 118322. Doi: 10.1016/j.carbpol.2021.118322.
[20]
LYU F J, LIU J, YUAN X, et al. The Preparation of Baicalin-Chitosan-Nanoparticles by Ion-Induced Combi- ning Chemical Crosslinking. J Quanzhou Normal Univ(泉州师范学院学报), 2020, 38(2):1-8.
[21]
LIU L N. Antitumor activity of doxorubicin conjugated stearic acid-g-chitosan oligosaccharide polymeric micelles . Hangzhou: Zhejiang University, 2010.
[22]
WU R J, YU R F, YAN X X, et al. Preparation and in vitro evaluation of arsenic trioxide loaded pH responsive poly(lactic-co-glycolic acid) nanoparticles. Chin Tradit Herb Drugs(中草药), 2021, 52(15):4528-4536.
2023, Vol. 58 
