Open AccessRepaglinide‐loaded long‐circulating biodegradable nanoparticles: Rational approach for the management of type 2 diabetes mellitus
Author(s) -
JAIN Shelesh,
SARAF Swarnlata
Publication year - 2009
Publication title -
journal of diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.949
H-Index - 43
eISSN - 1753-0407
pISSN - 1753-0393
DOI - 10.1111/j.1753-0407.2008.00001.x
Subject(s) - repaglinide , medicine , diabetes mellitus , in vivo , bioavailability , type 2 diabetes mellitus , streptozotocin , zeta potential , pharmacology , meal , drug delivery , endocrinology , type 2 diabetes , nanoparticle , nanotechnology , materials science , microbiology and biotechnology , biology
Background: Repaglinide (RPG) is an oral hypoglycemic agent with excellent bioavailability (90–98%) and a short plasma half‐life (2–6 h). A full dose of RPG is required before each meal; hence, therapy may become inconvenient. Thus, the aim of the present study was to design a novel delivery system to maintain peak plasma levels of RPG for the long‐term management of diabetes mellitus. Methods: Two nanoparticle formulations were prepared by combining RPG with poly (lactic‐co‐glycolic) acid alone or as a copolymer with methoxypolyethylene glycol (RPGNP1 and RPGNP2, respectively); both formulations were subjected to in vitro and in vivo characterization. In vivo characterization was performed in a streptozotocin (STZ)‐induced diabetic male albino rats. Results: The mean particle size of the RPGNP1 and RPGNP2 formulations was 387.8 ± 11.9 and 310.2 ± 12.4 nm, respectively, with a zeta potential of −27.4 ± 0.7 and −15.7 ± 0.5 mV, respectively. The entrapment efficiency and drug content of RPGNP1 (58.7 ± 1.3% and 27.4 ± 2.3%, respectively) was better than that of RPGNP2 (45.8 ± 1.2% and 24.3 ±1.1%, respectively). Blood glucose levels of RPGNP1‐ and RPGNP2‐treated STZ‐diabetic rats were reduced significantly (to normal levels) compared with untreated STZ‐diabetic rats ( P < 0.05), but there was no difference between the two treatment groups ( P > 0.05). However, whereas RPGNP1 was effective for a period of only 24 h, RPGNP2 was effective for up to 1 week. Conclusions: The results of the present study show that RPGNP2 effectively manages type 2 diabetes mellitus for up to 1 week. Surface‐modified NPs could be used to improve patient compliance with drug treatment as a result of decreased dosing frequency.