Insulin-loaded microcapsules for in vivo delivery.
Microencapsulation of insulin has been difficult, due to the high sensitivity of insulin to the harsh conditions that can occur during the microencapsulation process. We have developed a method of preparing insulin-loaded microcapsules by using a monoaxial ultrasonic atomizer to form microdroplets of insulin in aqueous solution surrounded by poly(lactic-co-glycolic acid) (PLGA) solution. Administration of these insulin-loaded microcapsules to type 1 diabetic rats maintained plasma insulin concentrations for 30 days, due to the sustained insulin release properties of the microcapsules. In contrast, plasma insulin concentrations after subcutaneous injection of insulin solution reached near zero levels within 2 days. Insulin solution showed only an immediate pharmacological effect, with no reduction of glycemia after 3 days, whereas insulin-loaded microcapsules maintained blood glucose levels at 100-200 mg/dL for 55 days. Molecular imaging using fluorescein isothiocyanate (FITC)-insulin-loaded microcapsules showed in vivo sustained release of the FITC-insulin in microcapsules. Using insulin-loaded microcapsules, we observed inflammation only immediately after injection, indicating that the rats adapted to long-term insulin release. In conclusion, insulin-loaded microcapsules may reduce nonrepetitive insulin administration and show sustained pharmacological performance.
Kim
Byung Soo
BS
Fusion Biotechnology Research Center, Korea Research Institute of Chemical Technology, P.O. Box 107, Yuseong, Daejeon 305-600, Korea.
Oh
Jae Min
JM
Hyun
Hoon
H
Kim
Kyung Sook
KS
Lee
Sang Hyo
SH
Kim
Yu Han
YH
Park
Kinam
K
Lee
Hai Bang
HB
Kim
Moon Suk
MS
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002214:Capsules; D003692:Delayed-Action Preparations; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000188:drug therapy*; D016503:Drug Delivery Systems; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D006016:Glycolates / Q000737:chemistry; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D019344:Lactic Acid; D008297:Male; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D002214:Capsules; D003692:Delayed-Action Preparations; D006016:Glycolates; D007328:Insulin; C031573:insulin, fluorescein-isothiocyanated-; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D016650:Fluorescein-5-isothiocyanate