| Title | Biopharmaceutical characterisation of insulin and recombinant human growth hormone loaded lipid submicron particles produced by supercritical gas micro-atomisation. | | Author(s) | Salmaso S, Bersani S, Elvassore N, Bertucco A, Caliceti P | | Institution | Department of Pharmaceutical Sciences, University of Padua-Via F. Marzolo, 5-35131 Padua-Italy. | | Source | Int J Pharm 2009 Jun 19. | | Abstract | Homogeneous dispersions of insulin and recombinant human growth hormone (rh-GH) in tristearin/phosphatidylcholine/PEG mixtures (1.3:1.3:0.25.0.15 w/w ratio) were processed by supercritical carbon dioxide gas micro-atomisation to produce protein-loaded lipid particles. The process yielded spherical particles, with a 197+/-94nm mean diameter, and the insulin and rh-GH recovery in the final product was 57+/-8% and 48+/-5%, respectively. In vitro, the proteins were slowly released for about 70-80hours according to a diffusive mechanism. In vivo, the insulin and glucose profiles in plasma obtained by subcutaneous administration of a dose of particles containing 2mug insulin to diabetic mice overlapped that obtained with 2mug of insulin in solution. Administration of a dose of particles containing 5mug insulin resulted in faster and longer glycaemia reduction. Oral administration of 20 and 50mug insulin equivalent particles produced a significant hypoglycaemic effect. The glucose levels decreased since 2hours after administration, reaching about 50% and 70% glucose reduction in 1-2hours with the lower and higher dose, respectively. As compared to subcutaneous administration, the relative pharmacological bioavailability obtained with 20 and 50mug equivalent insulin particles was 7.7% and 6.7%, respectively. Daily subcutaneous administration of 40mug of rh-GH-loaded particles to hypophysectomised rats induced similar body weight increase as 40mug rh-GH in solution. The daily oral administration of 400mug rh-GH equivalent particles elicited a slight body weight increase, which corresponded to a relative pharmacological bioavailability of 3.4% compared to subcutaneous administration. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19545616 |
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