Improving oral absorption of Salmon calcitonin by trimyristin lipid nanoparticles.
Solid lipid nanoparticles (SLN) composed of trimyristin (solid lipid) and poloxamer 407 (surfactant) were prepared by a w/o/w emulsion technique for the incorporation of Salmon calcitonin, and further explored as protein carriers for oral delivery. Trimyristin SLN showed a mean size diameter of 200 nm with an association efficiency for calcitonin of approx. 86%. The morphology of SLN was investigated by cryo-SEM and by AFM, revealing spheroid shape SLN with a smooth surface. The in vitro release of calcitonin occurred for a period of 8 h, under both gastric and intestinal simulated pH conditions, predicting suitable properties for oral administration. The pharmacological activity of the protein was evaluated following oral dosage of calcitonin-loaded SLN in rats. SLN lowered the basal blood calcium levels by up to 20% with 500 IU/kg dose sustaining hypocalcaemia over 8 h. The results indicate that incorporation of Salmon calcitonin into trimyristin SLN is a key factor for the improvement of the efficiency of such carriers for oral delivery of proteins.
Martins
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Faculty of Pharmacy, University of Porto, Rua Aníbal Cunha 164, 4050-030 Porto, Portugal.
Silva
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D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D002116:Calcitonin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D003460:Crystallization / Q000379:methods; D008055:Lipids / Q000737:chemistry*; D046911:Macromolecular Substances / Q000737:chemistry; D008297:Male; D008422:Materials Testing; D008968:Molecular Conformation; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012474:Salmon / Q000378:metabolism*; D013499:Surface Properties; D014280:Triglycerides / Q000737:chemistry*
D008055:Lipids; D046911:Macromolecular Substances; D014280:Triglycerides; C036694:trimyristin; D002116:Calcitonin