[Study on preparation and pharmacodynamics of insulin-loaded polyester microparticles].
OBJECTIVE
To investigate the possibility of using poly (epsilon-caprolactone-block-D, L-lactide) (PLCA) as a kind of materials to prepare the microparticles drug carrier.


METHODS
PCLA-MP (microparticle, MP) was prepared by double-emulsification solvent evaporation method. Its morphology was examined by scanning electron microscope. Its size diameter was examined by particle analyser. Insulin (INS), as a model drug, was then encapsulated into PCLA-MP (INS-PCLA-MP). HPLC method was established for determining INS in INS-PCLA-MP. An "antibody-capture" procedure was devised for investigating encapsulation mechanism. The in vitro release behaviour of INS-PCLA-MP was determined in phosphatic buffer solution (pH 7.4). The diabetic rat model was established and blood glucose levels were measured using glucose oxidase (GOD-PAP) method to evaluate the hypoglycaemic effects after subcutaneous administration of INS-PCLA-MP. The pharmacological bioavailability (PBA) of INS-PCLA-MP was calculated from the area above the curve (AAC) in contrast with INS-solution.


RESULTS
The mean diameter of INS-PCLA-MP was 1.9 microns, while the encapsulation ratio of INS reached to 76.46%. Only 18.25% encapsulated INS was on the surface of the microparticles, it could be measured by "antibody-capture" experiment. The in vitro release curve of INS-PCLA-MP consists of initial rapid release stage followed by slower exponential stage. In pharmacodynamic studies, after subcutaneous administration of INS-PCLA-MP 12 u.kg-1, the hypoglycaemic effect was significant. The PBA of INS-PCLA-MP was 123.08%.


CONCLUSIONS
PCLA might become a new drug carrier material in the future.
Ma
L M
LM
Department of Pharmacy, People's Hospital of Beijing Medical University, Beijing 100044, China.
Zhang
Q
Q
Li
Y Z
YZ
Gu
Z W
ZW
D000818:Animals; D001789:Blood Group Antigens / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D004337:Drug Carriers / Q000008:administration & dosage; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008863:Microspheres; D010316:Particle Size; D011108:Polymers; D051381:Rats; D017208:Rats, Wistar
D001789:Blood Group Antigens; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D011108:Polymers