Hydrophobic ion pairing of a GLP-1 analogue for incorporating into lipid nanocarriers designed for oral delivery

Autor: Andreas Bernkop-Schnürch, Ruba Ismail, Flavia Laffleur, Thi Nhu Quynh Phan, Ildikó Csóka
Rok vydání: 2020
Předmět:
Male
Membrane permeability
Pharmaceutical Science
Administration
Oral
Biological Availability
02 engineering and technology
behavioral disciplines and activities
030226 pharmacology & pharmacy
Glycerides
Polyethylene Glycols
Rats
Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
Surface-Active Agents
0302 clinical medicine
Drug Delivery Systems
Pulmonary surfactant
Bromide
Glucagon-Like Peptide 1
mental disorders
Animals
Humans
chemistry.chemical_classification
Dioctyl Sulfosuccinic Acid
Drug Carriers
Chemistry
Cationic polymerization
General Medicine
021001 nanoscience & nanotechnology
Lipids
Propylene Glycol
Bioavailability
Rats
Solubility
Lipophilicity
Tacrine
Exenatide
Nanoparticles
Nanocarriers
Counterion
Caprylates
0210 nano-technology
Hydrophobic and Hydrophilic Interactions
Biotechnology
Nuclear chemistry
Zdroj: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 152
ISSN: 1873-3441
Popis: The lipophilic character of peptides can be tremendously improved by hydrophobic ion pairing (HIP) with counterions to be efficiently incorporated into lipid-based nanocarriers (NCs). Herein, HIPs of exenatide with the cationic surfactant tetraheptylammonium bromide (THA) and the anionic surfactant sodium docusate (DOC) were formed to increase its lipophilicity. These HIPs were incorporated into lipid based NCs comprising 41% Capmul MCM, 15% Captex 355, 40% Cremophor RH and 4% propylene glycol. Exenatide-THA NCs showed a log Dlipophilic phase (LPh)/release medium (RM) of 2.29 and 1.92, whereas the log DLPh/RM of exenatide-DOC was 1.2 and −0.9 in simulated intestinal fluid and Hanks’ balanced salts buffer (HBSS), respectively. No significant hemolytic activity was induced at a concentration of 0.25% (m/v) of both blank and loaded NCs. Exenatide-THA NCs and exenatide-DOC NCs showed a 10-fold and 3-fold enhancement in intestinal apparent membrane permeability compared to free exenatide, respectively. Furthermore, orally administered exenatide-THA and exenatide-DOC NCs in healthy rats resulted in a relative bioavailability of 27.96 ± 5.24% and 16.29 ± 6.63%, respectively, confirming the comparatively higher potential of the cationic surfactant over the anionic surfactant. Findings of this work highlight the potential of the type of counterion used for HIP as key to successful design of lipid-based NCs for oral exenatide delivery.
Databáze: OpenAIRE
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