A proof-of-concept for developing oral lipidized peptide Nanostructured Lipid Carrier formulations
The aim of the study was to develop a protocol to encapsulate lipidized-peptides in Nanostructured Lipid Carrier (NLC) by High Pressure Homogenization (HPH) for oral delivery.
The impact of composition, pressure and number of cycles on particle size, polydispersity index (PDI), and stability was studied. The lipophilicity of two model peptides, Desmopressin (DES) and Leuprolide (LEU) was increased by formation of a Hydrophobic Ion Pair (HIP) with sodium docusate. The precipitation efficiency was 94.96 ± 0.27% and 99.92 ± 0.08% respectively.
Their solubility was evaluated in lipidic excipients. NLC were formed by pre-emulsion and HPH at 70 °C. Blank NLC of 95 ± 3 nm with a PDI of 0.14 ± 0.01 were obtained using 10% (w/v) Precirol®ATO5, 4% Kolliphor®RH40 and 5% Capryol™90. The particles were obtained after 3 min pre-emulsion at 11 000 rpm followed by 5 cycles at 500 bar on Microfluidizer® at 70 °C and finally 10 min in at 4 °C under stirring.
The complexes were successfully encapsulated in the developed NLC. HPLC analysis attested that peptides were not degraded by the process. The encapsulation efficiency (EE) was highly dependent on the Log P of the HIP with an EE of 10.7 ± 2.2% for DES-docusate HIP (log P = 0.5) and 84.7 ± 2.0% for LEU-docusate HIP (log P = 3). More on oral lipidized peptide nanostruactured lipid carriers