Microemulsions for oral delivery of insulin: design, development and evaluation in streptozotocin induced diabetic rats.
Insulin loaded microemulsions were developed adopting a low shear reverse micellar approach using didoceyldimethylammonium bromide (DMAB) as the surfactant, propylene glycol (PG) as the co-surfactant, triacetin (TA) as the oil phase and insulin solution as the aqueous phase. A ternary phase diagram was constructed based on multiple cloud point titration to highlight the reverse micellar region. The droplet sizes of the microemulsions were 161.7±24.7nm with PDI of 0.447±0.076 and insulin entrapment of ∼85%. Transmission electron microscopy (TEM) revealed the spherical nature and size homogeneity of the microemulsion droplets. The conformational stability of the entrapped insulin within microemulsions was confirmed by fluorescence spectroscopy and circular dichroism. The microemulsions displayed a 10-fold enhancement in bioavailability compared with plain insulin solution administered per oral in healthy rats. The short-term in vivo efficacy in STZ induced diabetic rats provided the proof of concept by a modest glucose reduction at a dose of 20IU/kg. Together this preliminary data indicate the promise of microemulsions for oral delivery of insulin.
Sharma
G
G
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
Wilson
K
K
van der Walle
C F
CF
Sattar
N
N
Petrie
J R
JR
Ravi Kumar
M N V
MN
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001786:Blood Glucose / Q000187:drug effects; D002942:Circular Dichroism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004655:Emulsions; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D019946:Propylene Glycol / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013050:Spectrometry, Fluorescence; D013311:Streptozocin; D014215:Triacetin / Q000737:chemistry
D001786:Blood Glucose; D004655:Emulsions; D007004:Hypoglycemic Agents; D007328:Insulin; D000644:Quaternary Ammonium Compounds; C046112:didodecyldimethylammonium; D013311:Streptozocin; D019946:Propylene Glycol; D014215:Triacetin