A novel approach to prepare insulin-loaded poly(lactic-co-glycolic acid) microcapsules and the protein stability study.
The purpose of this study was to propose a new preparation method to fabricate insulin-loaded poly(lactic-coglycolic acid) (PLGA) microparticles satisfying protein loading, release profiles, burst release, and particularly stability of the encapsulated protein. Insulin-loaded microcapsules were produced by a single phase o/o solvent evaporation method. The characteristics of the microcapsules were determined by various methods: the surface morphology and size of microparticles by atomic force microscopy and scanning electron microscopy, insulin crystalinity and drug-polymer interactions by XRD, DSC, and FTIR, chemical integrity and aggregation of insulin using HPLC and SDS-PAGE, the protein secondary structure by far ultraviolet-circular dichroism (CD), the antigenicity activity of insulin with ELISA techniques. PLGA microparticles showed smooth surfaces with microcapsule. Encapsulation efficiency of 51% and constant insulin release rate with initial insulin burst release of 24% was obtained. Encapsulated and released insulin was in the intact form and it was dispersed in crystalline state in the polymer matrix. Ease of manufacturing under mild preparation conditions, high level of drug entrapment, desirable release pattern with relatively low initial burst effect and an ability to preserve protein structure are the advantages which are offered by the developed protein encapsulation method.
School of Pharmacy and Pharmaceutical Sciences, Isfahan Pharmaceutical Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. emami@pharm.mui.ac.ir
Jaber
J
Emami
Hamed
H
Hamishehkar
Abdolhossien Rouholamini
AR
Najafabadi
Kambiz
K
Gilani
Mohsen
M
Minaiyan
Hamid
H
Mahdavi
Ali
A
Nokhodchi
D002152:Calorimetry, Differential Scanning; D002214:Capsules; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D004355:Drug Stability; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005079:Excipients; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry*; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
D002214:Capsules; D005079:Excipients; D007004:Hypoglycemic Agents; D007328:Insulin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid