The influence of lipid characteristics on the formation, in vitro release, and in vivo absorption of protein-loaded SLN prepared by the double emulsion process.
OBJECTIVE
To study the influence of lipid characteristics on the formation, in vitro release, and in vivo absorption of solid lipid nanoparticles (SLN) prepared by the double emulsion method.


METHODS
Stearic acid (SA), octadecyl alcohol (OA), cetyl palmitate (CP), glyceryl monostearate (GM), glyceryl palmitostearate (GP), glyceryl tripalmitate (GT), and glyceryl behenate (GB) were selected as the representatives of different kinds of lipids, insulin and thymopentin (TP5) were selected as the model protein drugs. Before preparation, the contact angles between water and lipids were determined to investigate their hydrophobicity. The influence of lipid hydrophobicity or lipid solution viscosity on the preparation of primary emulsion, double emulsion, and SLN were studied by evaluating the particle size, state, and stability of the systems. CP-SLN, GT-SLN, and GP-SLN were selected to be loaded with insulin and TP5 for the in vitro release and in vivo absorption examination. After oral administration to diabetic rats, the pharmacological availability (PA) of insulin-CP-SLN, insulin-GP-SLN, and insulin-GT-SLN were determined.


RESULTS
The hydrophobicity order of the lipids was GM<GP<GT<GB<SA<OA<CP. SLNs could be prepared successfully by CP, GT, and GP, and their particle size was 447.5 ± 50.8, 444.8 ± 72.5, and 213.7 38.4 nm, respectively. All of the three SLNs exhibited burst release, and the percentage insulin released in 4 hours from these three SLNs were 76.37%, 45.36%, and 33.28%, respectively, and the corresponding TP5 release percentages were 75.72%, 56.89%, and 47.43%. Particle sizes increased significantly for CP-SLN and GP-SLN after a 24 hours release study in simulated gastrointestinal fluid. The PA of insulin-CP-SLN, insulin-GT-SLN, and insulin-GP-SLN were 2.92%, 3.44%, and 4.53%, respectively.


CONCLUSIONS
This study suggested that GP with a suitable hydrophobicity, relatively lower burst release, and higher PA was the most promising lipid material of SLN for oral delivery of proteins.
Yang
Rui
R
College of Pharmacy, Shenyang Pharmaceutical University, Shen Yang, China.
Gao
Renchao
R
Li
Fang
F
He
Haibing
H
Tang
Xing
X
D000284:Administration, Oral; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D004655:Emulsions; D005079:Excipients / Q000737:chemistry; D041981:Gastrointestinal Tract / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008055:Lipids / Q000737:chemistry*; D008297:Male; D053758:Nanoparticles; D010316:Particle Size; D011506:Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D016305:Thymopentin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014783:Viscosity
D004337:Drug Carriers; D004655:Emulsions; D005079:Excipients; D007328:Insulin; D008055:Lipids; D011506:Proteins; D016305:Thymopentin