Preparation and in vivo evaluation of insulin-loaded biodegradable nanoparticles prepared from diblock copolymers of PLGA and PEG

The aim of this study was to design a controlled release vehicle for insulin to preserve its
stability and biological activity during fabrication and release. A modified, double emulsion,
solvent evaporation, technique using homogenisation force optimised entrapment efficiency of
insulin into biodegradable nanoparticles (NP) prepared from poly (dl-lactic-co-glycolic acid)
(PLGA) and its PEGylated diblock copolymers. Formulation parameters (type of polymer and
its concentration, stabiliser concentration and volume of internal aqueous phase) and
physicochemical characteristics (size, zeta potential, encapsulation efficiency, in vitro release
profiles and in vitro stability) were investigated. In vivo insulin sensitivity was tested by dietinduced
type II diabetic mice. Bioactivity of insulin was studied using Swiss TO mice with
streptozotocin-induced type I diabetic profile. Insulin-loaded NP were spherical and negatively
charged with an average diameter of 200–400 nm. Insulin encapsulation efficiency increased
significantly with increasing ratio of co-polymeric PEG. The internal aqueous phase volume
had a significant impact on encapsulation efficiency, initial burst release and NP size.
Optimised insulin NP formulated from 10% PEG-PLGA retained insulin integrity in vitro,
insulin sensitivity in vivo and induced a sustained hypoglycaemic effect from 3 hours to 6 days
in type I diabetic mice.