Orally delivered salmon calcitonin-loaded solid lipid nanoparticles prepared by micelle-double emulsion method via the combined use of different solid lipids.
OBJECTIVE
The purpose of this study was to develop a new orally delivered nanoparticulate system to improve the bioavailability of salmon calcitonin (sCT).


METHODS
Four sCT-loaded solid lipid nanoparticles (SLNs) were prepared successfully by micelle-double emulsion technique via either the sole use of stearic acid (SA) or the combined use of SA and triglycerides (including tripalmitin [TP], trimyristin or trilaurin).


RESULTS
Compared with other SLNs, the combination of SA and TP could not only significantly improve the colloidal stability of SLNs and enhance the drug stability in the simulated intestinal fluids, but also intensively increase the intracellular uptake of drugs compared with the other SLNs (p < 0.05). The mechanism of internalization was an active transport involved in clathrin- and caveolae-dependent endocytosis. In vivo, the sCT SLNs prepared with SA and TP exhibited the highest reduction of plasma Ca(2+) level (17.44 ± 3.68%) with a bioavailability of 13.01 ± 3.24%.


CONCLUSIONS
The SLNs formed by SA and TP as the solid lipids may be a promising carrier for oral delivery of peptide drugs.
Key Laboratory of Drug Targeting & Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Number 17 Block 3 Southern Renmin Road, Chengdu, China.
Chunhui
C
Chen
Tingting
T
Fan
Yun
Y
Jin
Zhou
Z
Zhou
Yang
Y
Yang
Xi
X
Zhu
Zhi-Rong
ZR
Zhang
Qiang
Q
Zhang
Yuan
Y
Huang
D000818:Animals; D018938:Caco-2 Cells; D002116:Calcitonin / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D008962:Models, Theoretical; D053758:Nanoparticles / Q000737:chemistry*; D011509:Proteoglycans / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000737:chemistry
D008055:Lipids; D008823:Micelles; D011509:Proteoglycans; D014280:Triglycerides; C004565:trilaurin; C028815:salmon calcitonin; C026064:aggregoserpentin; D002116:Calcitonin; C005859:tripalmitin