Background: Bioavailability of peptide/protein drugs is extremely low after oral administration due to their instability in the gastrointestinal tract or poor absorption.
Objective and hypotheses: Oral delivery of growth hormone and somatostatin by adding extreme stable lipids.
Method: A liposomal system based on a combination of standard lipids and membrane spanning tetraether lipids, which are extremely stable biomolecules. The somatostatin analogue Octreotide (Sandostatin) and human growth hormone (hGH) were used as model drugs. The bioavailability of Octreotide and hGH was determined after administration of peptide loaded liposomes to rats via gavage and of peptide alone via i.v. injection.
Results: The shape of the liposomes was characterized by freeze fracture electron microscopy and light scattering particle size analysis showing an average diameter of 100150 nm. The release properties and stability of these liposomes was studied after incubation in artificial gastric and intestinal fluids. The liposomes containing tetraether lipids showed a significantly increased stability compared to standard liposomes. Further optimized by incorporation of the liposomes into a jelly matrix generated a solid dosage form being stable for up to 1 year, from which liposomes could be released in the GI-tract. The absolute bioavailability of Octreotide was increased by a factor of 2530 after administration of tetraether lipid liposomes, the bioavailability of hGH was increased by a factor of 360, both resulting in therapeutically relevant plasma concentrations.
Conclusion: Formulation of peptides in tetraether liposomes increases the bioavailability of peptidic drugs after oral administration.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology