Relationship between drug effects and particle size of insulin-loaded bioadhesive microspheres.Acta Pharmacol Sin. 2002 Nov; 23(11):1051-6.AP
To formulate and characterize insulin-loaded adhesive microspheres (MP) and evaluate drug effects of MP with various sizes, 120, 350, and 1000 nm in diameter, in the alloxan-induced diabetic rats.
Insulin-loaded MP were formulated by an ionotropic gelation procedure. Particle size distributions were determined by photon correlation spectroscopy and optical microscopy. The factors that influenced the particle sizes and loading capacity were investigated, and the release properties were assessed in vitro. The hypoglycemic effect was investigated by monitoring the plasma glucose level of the alloxan-induced diabetic rats after oral administration.
All the MPs with three sizes formulated were in the desired size range, and the loading capacity was 15.3 %+/-1.7 % (120 nm), 32.4 %+/-2.4 % (350 nm), and 53.3 %+/-2.7 % (1000 nm) respectively. The particle size also had an influence on the release property of the MPs. Half an hour later, 25 %+/-4 % (120 nm), 18.3 %+/-2.4 % (350 nm), and 8.6 %+/-1.3 % (1000 nm) of insulin were released. MP with different sizes had various degree of hypoglycemic effects after 10 h (P<0.05 vs control insulin solution). The plasma glucose level of 350 nm size particles remarkably decreased 15 h later (P<0.05 vs 120 nm) or 35 h later (P<0.01 vs others). The relative pharmacological availability was 10.2 %+/-0.5 % (120 nm), 14.9 %+/-1.3 % (350 nm), and 7.3 %+/-0.8 % (1000 nm) respectively. Particles of 350 nm showed a comparatively higher availability (P<0.05).
Adhesive CS-MP were helpful in increasing the relative pharmacological bioavailability of insulin, and a distinct advantage of proper particle size helped to increase the drug effects.