Insulin- and cholic acid-loaded zein/casein-dextran nanoparticles enhance the oral absorption and hypoglycemic effect of insulin

被引:46
作者
Bao, Xiaoyan [1 ]
Qian, Kang [2 ]
Yao, Ping [1 ]
机构
[1] Fudan Univ, Dept Macromol Sci, Collaborat Innovat Ctr Polymers & Polymer Composi, State Key Lab Mol Engn Polymers, Shanghai 200438, Peoples R China
[2] Fudan Univ, Sch Pharm, Key Lab Smart Drug Delivery, Minist Educ, Shanghai 201203, Peoples R China
基金
中国国家自然科学基金;
关键词
DRUG-DELIVERY-SYSTEMS; MUCUS; ZEIN; TRANSPORT; LIVER; EPITHELIUM; DIFFUSION; OVERCOME; RELEASE; BARRIER;
D O I
10.1039/d1tb00806d
中图分类号
TB3 [工程材料学]; R318.08 [生物材料学];
学科分类号
0805 ; 080501 ; 080502 ;
摘要
Diabetes mellitus is the most common metabolic disease in the world. Herein, insulin- and cholic acid-loaded zein nanoparticles with dextran surfaces were fabricated to enhance the oral absorptions of insulin in the intestine and in the liver which is the primary action organ of endogenous insulin. In the nanoparticles, zein acted as cement to embed insulin, cholic acid and casein by hydrophobic interactions. The hydrophilic dextran conjugated to casein by the Maillard reaction was located on the nanoparticle surface. The nanoparticles had an insulin loading efficiency of 74.6%, a cholic acid loading efficiency of 55.1% and a hydrodynamic diameter of 267 nm. The dextran significantly increased the disperse stability of the nanoparticles, protected the loaded insulin from hydrolysis in digestive juices, and increased the trans-mucus permeability of the insulin. The embedded cholic acid molecules were consecutively exposed to the surface when the nanoparticles were gradually eroded by proteases. The exposed cholic acid promoted the absorptions of the nanoparticles in the ileum and liver via bile acid transporters. The effect of pretreated lymphatic transport inhibitor cycloheximide revealed that about half of the nanoparticles were transported via the intestinal lymphatic transport pathway and the other half of the nanoparticles were transported via portal blood absorption. The oral pharmacological bioavailability of the nanoparticles in type I diabetic mice was 12.5-20.5%. This study demonstrates that nanoparticles are a promising oral delivery system for insulin.
引用
收藏
页码:6234 / 6245
页数:12
相关论文
共 55 条
[1]   Standards of Medical Care in Diabetes-2014 [J].
不详 .
DIABETES CARE, 2014, 37 :S14-S80
[2]   The effects of repeated oral gavage on the health of male CD-1 mice [J].
Arantes-Rodrigues, Regina ;
Henriques, Andreia ;
Pinto-Leite, Rosario ;
Faustino-Rocha, Ana ;
Pinho-Oliveira, Jacinta ;
Teixeira-Guedes, Catarina ;
Seixas, Fernanda ;
Gama, Adelina ;
Colaco, Bruno ;
Colaco, Aura ;
Oliveira, Paula A. .
LAB ANIMAL, 2012, 41 (05) :129-134
[3]  
Arbit Ehud, 2004, Diabetes Technol Ther, V6, P510, DOI 10.1089/1520915041705929
[4]   Oral delivery of exenatide-loaded hybrid zein nanoparticles for stable blood glucose control and β-cell repair of type 2 diabetes mice [J].
Bao, Xiaoyan ;
Qian, Kang ;
Yao, Ping .
JOURNAL OF NANOBIOTECHNOLOGY, 2020, 18 (01)
[5]   Mechanisms of transport of polymeric and lipidic nanoparticles across the intestinal barrier [J].
Beloqui, Ana ;
des Rieux, Anne ;
Preat, Veronique .
ADVANCED DRUG DELIVERY REVIEWS, 2016, 106 :242-255
[6]   Zinc, insulin and diabetes [J].
Chausmer, AB .
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION, 1998, 17 (02) :109-115
[7]   Processes improving the dispersibility of spray-dried zein nanoparticles using sodium caseinate [J].
Chen, Huaiqiong ;
Zhong, Qixin .
FOOD HYDROCOLLOIDS, 2014, 35 :358-366
[8]   Section 3: Phasic insulin release and metabolic control - Physiological consequences of phasic insulin release in the normal animal [J].
Cherrington, AD ;
Sindelar, D ;
Edgerton, D ;
Steiner, K ;
McGuinness, OP .
DIABETES, 2002, 51 :S103-S108
[9]   Evaluation of a chylomicron flow blocking approach to investigate the intestinal lymphatic transport of lipophilic drugs [J].
Dahan, A ;
Hoffman, A .
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2005, 24 (04) :381-388
[10]   Effect of Maillard Conjugates on the Physical Stability of Zein Nanoparticles Prepared by Liquid Antisolvent Coprecipitation [J].
Davidov-Pardo, Gabriel ;
Joye, Iris J. ;
Espinal-Ruiz, Mauricio ;
McClements, David Julian .
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2015, 63 (38) :8510-8518