Original Article

Relationship between drug effects and particle size of insulin-loaded bioadhesive microspheres.

Yan PAN, Jun-Min ZHENG, Hui-Ying ZHAO, Ying-Jian LI, Hui XU, Gang WEI


AIM: 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.
METHODS: 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.
RESULTS: 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
CONCLUSION: 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.

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