Biomimetic thiamine- and niacin-decorated liposomes for enhanced oral delivery of insulin.
10.1016/j.apsb.2017.11.007
- Author:
Haisheng HE
1
;
Yi LU
1
;
Jianping QI
1
;
Weili ZHAO
1
;
Xiaochun DONG
1
;
Wei WU
1
Author Information
1. Key Laboratory of Smart Drug Delivery of MOE and PLA, School of Pharmacy, Fudan University, Shanghai 201203, China.
- Publication Type:Journal Article
- Keywords:
1H NMR, 1H nuclear magnetic resonance;
AAC, area above the curve;
Biomimetic;
CDI, N,Nʹ-carbonyldiimidazole;
CH, cholesterol;
CH-Lip, conventional (cholesterol) liposomes;
DMAP, dimethylaminopyridine;
DMF, dimethylformamide;
Drug delivery;
EDC, N-ethyl-Nʹ-(3-dimethylaminopropyl) carbodiimide;
EE, entrapment efficiency;
ESI-MS, electrospray ionization mass spectrometry;
FAE, follicle-associated epithelia;
GIT, gastrointestinal tract;
HPLC/UV, high-performance liquid chromatography/ultraviolet;
INS, insulin;
Insulin;
Liposomes;
NA, niacin;
NA-Lip, niacin liposomes;
Niacin;
Oral;
SGF, simulated gastric fluid;
SIF, simulated intestinal fluid;
SPC, soybean phosphatidylcholine;
TH, thiamine;
TH-Lip, thiamine-decorated liposomes;
Thiamine;
USP, United States Pharmacopeia;
VB1, vitamin B1;
Vitamin
- From:
Acta Pharmaceutica Sinica B
2018;8(1):97-105
- CountryChina
- Language:English
-
Abstract:
Biomimetic nanocarriers are emerging as efficient vehicles to facilitate dietary absorption of biomacromolecules. In this study, two vitamins, thiamine and niacin, are employed to decorate liposomes loaded with insulin, thus facilitating oral absorption vitamin ligand-receptor interactions. Both vitamins are conjugated with stearamine, which works to anchor the ligands to the surface of liposomes. Liposomes prepared under optimum conditions have a mean particle size of 125-150 nm and an insulin entrapment efficiency of approximately 30%-36%. Encapsulation into liposomes helps to stabilize insulin due to improved resistance against enzymatic disruption, with 60% and 80% of the insulin left after 4 h when incubated in simulated gastric and intestinal fluids, respectively, whereas non-encapsulated insulin is broken down completely at 0.5 h. Preservation of insulin bioactivity against preparative stresses is validated by intra-peritoneal injection of insulin after release from various liposomes using the surfactant Triton X-100. In a diabetic rat model chemically induced by streptozotocin, both thiamine- and niacin-decorated liposomes showed a comparable and sustained mild hypoglycemic effect. The superiority of decorated liposomes over conventional liposomes highlights the contribution of vitamin ligands. It is concluded that decoration of liposomes with thiamine or niacin facilitates interactions with gastrointestinal vitamin receptors and thereby facilitates oral absorption of insulin-loaded liposomes.
