Evaluation of pharmacological efficacy of 'insulin-surfoplex' encapsulated polymer vesicles.
The present study has been designed to study whether formation of ion-pair complex or 'surfoplex' can enhance the pharmacological efficacy of protein-loaded PCL-PEG-based polymerosomes. Insulin was selected as the model protein and was complexed with sodium deoxycholate, a naturally occurring bile salt. The surfoplexes were characterized for extent and site of complexation, stability, mass and partition coefficient. The lipophilicity of insulin was enhanced 5-fold upon complexation resulting in an increase in entrapment efficiency by 10-50% for all formulations compared to free insulin. The release of insulin from the systems was also modulated with reduction in burst release by 30%. The surfoplex was found to be therapeutically active for 8h duration (C(max) serum insulin=64.15+/-13.28 mIU/mL) in diabetic rat model. However, pharmacological efficacy of the complex-loaded nanoparticles (Nps) did not show significant enhancement with respect to insulin-loaded systems. The study therefore suggests that while ion-pair complexes may improve the in vitro kinetics of protein-loaded carriers, their therapeutic potential is dependent on the intensity of interactions between the peptide chains and polymer matrix.
Rastogi
Rachna
R
II/192, Centre for Biomedical Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India.
Anand
Sneh
S
Koul
Veena
V
D000588:Amines / Q000737:chemistry; D000818:Animals; D001665:Binding Sites; D001682:Biological Availability; D001786:Blood Glucose / Q000187:drug effects; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D003840:Deoxycholic Acid / Q000737:chemistry*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D009391:Nephelometry and Turbidimetry; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011487:Protein Conformation; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization; D017550:Spectroscopy, Fourier Transform Infrared
D000588:Amines; D001786:Blood Glucose; D004337:Drug Carriers; D007328:Insulin; D011091:Polyesters; C515340:poly(epsilon-caprolactone)-b-poly(ethyleneglycol)-b-poly(epsilon-caprolactone); D003840:Deoxycholic Acid; D011092:Polyethylene Glycols