Abstract
In the previous study, chitosan-succinyl-prednisolone conjugate microparticles (MP) were found to exhibit good efficacy and reduced toxicity nearly as well as their Eudragit L-coated microparticles (MP/EuL). This proposes a question whether enteric-coating of MP is necessary or not. Although MP/EuL were already examined for their pharmacokinetic and gastrointestinal behaviors, MP have not been done yet. Therefore, in this study, MP were evaluated by investigating pharmacokinetic features in detail. MP with the in vitro features equivalent to those of the previous conjugate microparticles could be produced more readily in the modified preparative method. Pharmacokinetic and gastrointestinal behaviors of MP were investigated by intragastric dosing (5 mg PD eq./kg) to rats with 2,4,6-trinitrobenzenesulfonic acid-induced ulcerative colitis. The plasma concentration was suppressed extensively in MP as well as MP/EuL, supporting the reduction of PD systemic toxic side effects. However, the plasma level increased gradually up to 7 h in MP, but not in MP/EuL. At 8 h after dosing, MP were detected in the stomach to a fair extent, and free PD was found there, indicating that MP were subjected to trapping in the stomach probably due to positive charge of chitosan molecules. For MP, such prolonged localization and slow release of PD in the stomach were probably associated with the gradual increase in plasma concentration. Therefore, MP/EuL were evaluated to be superior to MP for effective targeting to ulcerative colitis. It is concluded that enteric-coating is very important for the targeting system using MP.
Highlights
Inflammatory bowel disease (IBD), represented by ulcerative colitis (UC) and Crohn’s disease (CD), has become a serious health problem for many developed countries
inflammatory bowel disease (IBD) is said to be induced by various factors such as genetic background, change in intestinal environment associated with enteric flora and disorder of intestinal immune system [1]-[3]
As PD causes severe toxic side effect considerably in a prolonged use or high dose, its use is generally limited [10] [11]. It is important for enhancement of efficacy and reduction of toxic side effect to deliver an anti-inflammatory drug to the diseased site
Summary
Inflammatory bowel disease (IBD), represented by ulcerative colitis (UC) and Crohn’s disease (CD), has become a serious health problem for many developed countries. As PD causes severe toxic side effect considerably in a prolonged use or high dose, its use is generally limited [10] [11] It is important for enhancement of efficacy and reduction of toxic side effect to deliver an anti-inflammatory drug to the diseased site . Small size particles (submicron-micron order size) and prolonged release are considered to be important in order to improve the drug function in the treatment of UC [19] [22] From such knowledge, PD-loaded microparticles have been developed using chitosan-suscinyl-predinisolone conjugate and enteric-coating polymer, Eudragit [23] [24].
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