Lectin-modified solid lipid nanoparticles as carriers for oral administration of insulin.
The aim of this study was to design and characterize lectin-modified solid lipid nanoparticles (SLNs) containing insulin and to evaluate the potential of the lectin-modified colloidal carriers for oral administration of peptide and protein drugs. SLNs were prepared by three different methods. For comparison, some insulin-loaded SLNs were modified with wheat germ agglutinin-N-glutaryl-phosphatidylethanolamine (WGA-N-glut-PE). The particle size, zeta potential and entrapment efficiency of insulin-loaded SLNs were determined. Insulin-loaded SLNs prepared by an appropriate modification of the double dispersion method yielded the highest drug entrapment efficiency, which was more than 60%. In vivo experiments were carried out using insulin-loaded SLNs and WGA-modified SLNs prepared by this method. SLNs and WGA-modified SLNs protected insulin against degradation by digestive enzymes in vitro. The stabilizing effect of WGA-modified SLNs was greater than that observed in SLNs. After oral administration of insulin-loaded SLNs or WGA-modified SLNs to rats, the relative pharmacological bioavailabilities were 4.46% and 6.08%, and the relative bioavailabilities were 4.99% and 7.11%, respectively, in comparison to subcutaneous injection of insulin. These results demonstrated that SLNs and WGA-modified SLNs promoted the oral absorption of insulin.
Zhang
Na
N
The Pharmaceutical College, Shandong University, 44 Wen hua Xi Lu, Ji'nan, Shandong Province, China.
Ping
Qineng
Q
Huang
Guihua
G
Xu
Wenfang
W
Cheng
Yanna
Y
Han
Xiuzhen
X
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001786:Blood Glucose / Q000032:analysis; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004355:Drug Stability; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D007408:Intestinal Absorption / Q000187:drug effects; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D014909:Wheat Germ Agglutinins / Q000008:administration & dosage* / Q000737:chemistry
D001786:Blood Glucose; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; C049392:N-glutarylphosphatidylethanolamine; D010714:Phosphatidylethanolamines; D014909:Wheat Germ Agglutinins