Effective incorporation of insulin in mucus permeating self-nanoemulsifying drug delivery systems.
The development of a novel, mucus permeating SNEDDS formulation for oral insulin delivery containing a hydrophobic ion pair of insulin/dimyristoyl phosphatidylglycerol (INS/DMPG) is presented. Three oil/surfactant/cosurfactant combinations and 27 weight ratios of oil, surfactant and cosurfactant for each combination were evaluated with the aid of ternary phase diagrams, for the incorporation of the protein/phospholipid complex. The developed formulation was characterized by an average droplet diameter of 30-45 nm. Depending on the initial protein concentration, the loading of insulin in SNEDDS varied between 0.27 and 1.13 wt%. The therapeutic protein was found to be efficiently protected from enzymatic degradation by intestinal enzymes (i.e., trypsin, α-chymotrypsin). The SNEDDS formulation exhibited increased mucus permeability and did not appear to be affected by ionic strength. The incorporation of INS/DMPG in SNEDDS prevented an initial burst release of insulin. INS/DMPG loaded SNEDDS were found to be non-cytotoxic up to a concentration of 2mg/ml. According to the reported results, the incorporation of the hydrophobic ion pair of INS/DMPG in SNEDDS could be regarded as a promising strategy for the oral delivery of insulin.
Department of Chemical Engineering, Aristotle University of Thessaloniki, P.O. Box 472, 54124 Thessaloniki, Greece.
Theodora
T
Karamanidou
Chemical Process & Energy Resources Research Institute, Centre for Research and Technology Hellas, P.O. Box 60361, 57001 Thessaloniki, Greece.
Konstantina
K
Karidi
Department of Chemical Engineering, Aristotle University of Thessaloniki, P.O. Box 472, 54124 Thessaloniki, Greece.
Vassilis
V
Bourganis
Department of Chemical Engineering, Aristotle University of Thessaloniki, P.O. Box 472, 54124 Thessaloniki, Greece; Chemical Process & Energy Resources Research Institute, Centre for Research and Technology Hellas, P.O. Box 60361, 57001 Thessaloniki, Greece.
Katerina
K
Kontonikola
Chemical Process & Energy Resources Research Institute, Centre for Research and Technology Hellas, P.O. Box 60361, 57001 Thessaloniki, Greece.
Olga
O
Kammona
Department of Chemical Engineering, Aristotle University of Thessaloniki, P.O. Box 472, 54124 Thessaloniki, Greece; Chemical Process & Energy Resources Research Institute, Centre for Research and Technology Hellas, P.O. Box 60361, 57001 Thessaloniki, Greece. Electronic address: costas.kiparissides@cperi.certh.gr.
Costas
C
Kiparissides
D000284:Administration, Oral; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004655:Emulsions; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009093:Mucus / Q000378:metabolism*; D053758:Nanoparticles; D010316:Particle Size; D010539:Permeability; D044367:Phase Transition; D010715:Phosphatidylglycerols / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry; D013552:Swine
D004337:Drug Carriers; D004655:Emulsions; D007328:Insulin; D010715:Phosphatidylglycerols; D013501:Surface-Active Agents; C002773:dimyristoylphosphatidylglycerol
Dimyristoyl phosphatidylglycerol; Insulin; Ionic complexation; Mucus; Oral delivery; SNEDDS