Effect of pore size of three-dimensionally ordered macroporous chitosan–silica matrix on solubility, drug release, and oral bioavailability of loaded-nimodipine

Abstract

Objective: To explore the effect of the pore size of three-dimensionally ordered macroporous chitosan–silica (3D-CS) matrix on the solubility, drug release, and oral bioavailability of the loaded drug.Methods: 3D-CS matrices with pore sizes of 180 nm, 470 nm, and 930 nm were prepared. Nimodipine (NMDP) was used as the drug model. The morphology, specific surface area, and chitosan mass ratio of the 3D-CS matrices were characterized before the effect of the pore size on drug crystallinity, solubility, release, and in vivo pharmacokinetics were investigated.Results: With the pore size of 3D-CS matrix decreasing, the drug crystallinity decreased and the aqueous solubility increased. The drug release was synthetically controlled by the pore size and chitosan content of 3D-CS matrix in a pH 6.8 medium, while in a pH 1.2 medium the erosion of the 3D-CS matrix played an important role in the decreased drug release rate. The area under the curve of the drug-loaded 3D-CS matrices with pore sizes of 930 nm, 470 nm, and 180 nm was 7.46-fold, 5.85-fold, and 3.75-fold larger than that of raw NMDP respectively.Conclusion: Our findings suggest that the oral bioavailability decreased with a decrease in the pore size of the matrix.