Release Characteristics and Pharmacokinetic Properties of Chitosan Coated Curcumin Ethosomes
LI Kai-ling1, LI Yuan2, ZHAO Jing3, CHEN Ran1, ZHANG Jing-qing1*
1. Chongqing Research Center for Pharmaceutical Engineering, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China; 2. Department of Pharmacy, Shuangliu Hospital of Traditional Chinese Medicine, Chengdu 610200, China; 3. Children's Hospital of Chongqing Medical University, Chongqing 400015, China
Abstract：OBJECTIVE To investigate the release characteristics in vitro of chitosan coated curcumin ethosomes (CMETS-CS) and its pharmacokinetics in rats. METHODS The in vitro cumulative release rate of CMETS-CS in two different media (pH 1.2 HCl and pH 6.8 PBS solution) was investigated by dynamic dialysis. The release behavior was evaluated by similar factor method. After gastrointestinal administration, the plasma drug concentration at different time point was determined by high performance liquid chromatography (HPLC), and the average plasma concentration-time curve was drawn. The pharmacokinetic parameters, bioequivalence between CMETS-CS and CM were analyzed by DAS software. RESULTS The cumulative release rates of CMETS-CS in pH 1.2 HCl and pH 6.8 PBS solution were (70.49±0.75)%, (73.90±0.52)%, respectively. Compared with CM, the CMETS-CS significantly increase the drug release.The release behavior of CMETS-CS in the two different release media was similar. After calculation, the area under the 0-72 h curve (AUC0-72 h), mean residence time (MRT0-72 h), peak concentration (ρmax) of CMETS-CS were 11.84, 5.45, 1.55 times than those of free curcumin (CM), respectively and its relative bioavailability of CMETS-CS was 1 111.32%. The bioequivalence of AUC0-72 h、AUC0-∞ and tmax and in CMETS-CS and CM were not eligible, but bioequivalence of ρmax was eligible. CONCLUSION Compared with free curcumin, CMETS-CS can improve the release behavior in vitro, significantly improve the oral bioavailability in rats, and there is not bioequivalence between CMETS-CS and CM.
WANNINGER S, LORENZ V, SUBHAN A, et al. Metal complexes of curcumin-synthetic strategies, structures and medicinal applications[J]. Chem Soc Rev, 2015,44(15):4986-5002.
[2]
WAN K, SUN L, HU X, et al. Novel nanoemulsion based lipid nanosystems for favorable in vitro and in vivo characteristics of curcumin[J]. Int J Pharm, 2016,504(1-2):80-88.
[3]
HUANG D X, YUAN Y Q, ZHU S, et al. Curcumin-loaded amphiphilic star-shaped polyester-based nanoparticles for drug delivery system by microchannels[J]. Chin Pharm J(中国药学杂志), 2018,53(2):114-121.
[4]
TAN Q, WU J, LI Y, et al. A supermolecular curcumin for enhanced antiproliferative and proapoptotic activities: molecular characteristics, computer modeling and in vivo pharmacokinetics[J]. Nanotechnology, 2013, 24(3):035102.
[5]
JIN H, PI J, ZHAO Y, et al. EGFR-targeting PLGA-PEG nanoparticles as a curcumin delivery system for breast cancer therapy[J]. Nanoscale, 2017,9(42):16365-16374.
[6]
MARQUARDT J U, GOMEZQ L, ARREGUIN C L, et al. Curcumin effectively inhibits oncogenic NF-κB signaling and restrains stemness features in liver cancer[J]. J Hepatol, 2015,63(3):661-669.
[7]
HOU T Y, DAVIDSON L A, KIM E, et al. Nutrient-gene interaction in colon cancer, from the membrane to cellular physiology[J]. Annu Rev Nutr, 2016,36:543-570.
[8]
BI W J, MU X J, ABULIMITE Z, et al. Progress in targeting-delivery systems for curcumin [J]. Chin Pharm J(中国药学杂志), 2015, 50(4):323-329.
[9]
PILCH E, MUSIAL W. Liposomes with an ethanol fraction as an application for drug delivery[J]. Int J Mol Sci, 2018,19(12): 3806.
[10]
YANG L, WU L, WU D, et al. Mechanism of transdermal permeation promotion of lipophilic drugs by ethosomes[J]. Int J Nanomed, 2017, 12:3357-3364.
[11]
VAN TRAN V, MOON J Y, LEE Y C. Liposomes for delivery of antioxidants in cosmeceuticals: challenges and development strategies[J]. J Controlled Release, 2019, 300:114-140.
[12]
QUAGLIARIELLO V, MASARONE M, ARMENIA E, et al. Chitosan-coated liposomes loaded with butyric acid demonstrate anticancer and anti-inflammatory activity in human hepatoma HepG2 cells[J]. Oncol Rep,2019,41(3):1476-1486.
[13]
WAN S L, LIU Y Y, LI Y, et al. Preliminary study on stability and pharmacokinetics of chitosan-modified L-asparaginase liposomes[J]. Chin Pharm J(中国药学杂志), 2017, 52(19):1706-1709.
[14]
ZHAO J, LI Y, SHI M X, et al. Pharmacokinetics of curcumin ethosomes in rats in vivo[J]. J Sichuan Univ (Med Sci Ed)(四川大学学报:医学版), 2017,48(2):290-294.
[15]
GONG X F, ZHANG D, WANG Y R, et al. Effects of alcohol on release characteristics of metformin hydrochloride extended-release tablets in vitro and in vivo[J]. Chin Pharm J(中国药学杂志), 2019,54(1):47-52.
[16]
YANG M, ZHANG J Q, WANG H,et al.Pharmacokinetics study of curcumin nanoemulsionin vitro and in vivo[J]. West China J Pharm Sci(华西药学杂志), 2016,31(2):174-177.
[17]
ZHAO J, LI Y, LI K L, et al. In vitro release characteristics and in vivo gastrointestinal absorption of curcumin ethosomes[J]. J Chongqing Med Univ(重庆医科大学学报), 2019,44(3):275-281.
[18]
LEE E H, LIM S J, LEE M K. Chitosan-coated liposomes to stabilize and enhance transdermal delivery of indocyanine green for photodynamic therapy of melanoma[J]. Carbohydr Polym, 2019,224:115143.
[19]
MU Y, FU Y, LI J, et al. Multifunctional quercetin conjugated chitosan nano-micelles with P-gp inhibition and permeation enhancement of anticancer drug[J]. Carbohydr Polym, 2019,203:10-18.
[20]
WEI Y, GUO J, ZHENG X, et al. Preparation,pharmacokinetics and biodistribution of baicalin-loaded liposomes[J]. Int J Nanomed, 2014,9:3623-3630.
[21]
ZHONG R L, XIA Z, WU J, et al. In vivo pharmacokinetics investigation of curcumin nanosuspensions in rats[J]. Chin J Exp Tradit Med Form(中国实验方剂学杂志), 2013,19(20):137-139.
2020, Vol. 55 
