title: A novel surface modified nitrendipine nanocrystals with enhancement of bioavailability and stability.
abstract: In this study, chitosan, a cationic polymer with positive charge, was introduced to modify the nanocrystals of nitrendipine with negative charge. The nanocrystals were prepared via precipitation-high pressure homogenization method. Then the nanocrystals were dispersed into chitosan solution, and the free chitosan was removed by centrifugation to obtain the chitosan modified nanocrystals, which remained the same particle size. However, the zeta-potential changed to positive after modification. The physical stability of the chitosan modified nanocrystals was remarkably improved under ambient conditions. During the in vitro dissolution test, the modified nanocrystals showed a certain degree of slow-release property. In the in vivo study, the C(max) of nitrendipine remained the same, however, the T(max) delayed from 0.75 h to 1.5 h with the chitosan modified nanocrystals. The surface modification by chitosan improved the bioavailability compared with the initial nanocrystals, which had demonstrated significant improvement of bioavailability compared to the traditional coarse powder form. Based on the experimental results, modification of the nanocrystals with certain polymer was supposed to be a good method to control the in vitro and in vivo behaviors of the nanocrystals, which could further increase the bioavailability of the water insoluble drug.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Science, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Quan
authors.forename: Kai
authors.initials: K
authors.lastname: Shi
authors.forename: Hongze
authors.initials: H
authors.lastname: Piao
authors.forename: Hongyu
authors.initials: H
authors.lastname: Piao
authors.forename: Na
authors.initials: N
authors.lastname: Liang
authors.forename: Dengning
authors.initials: D
authors.lastname: Xia
authors.forename: Fude
authors.initials: F
authors.lastname: Cui
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D002152:Calorimetry, Differential Scanning; D011232:Chemical Precipitation; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry; D003460:Crystallization; D018360:Crystallography, X-Ray; D003692:Delayed-Action Preparations; D004355:Drug Stability; D008297:Male; D053758:Nanoparticles; D036103:Nanotechnology; D009568:Nitrendipine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D048271:Chitosan; D009568:Nitrendipine