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Kinetic analysis of in vitro and in vivo release of prednisolone from the conjugate of glycol-chitosan and succinyl-prednisolone.

Abstract：

:Recently, many people have developed rheumatoid arthritis (RA), and prednisolone (PD) is often used for treatment; however, long use and a large dose of PD can cause toxic side effects. In this study, in order to enhance the therapeutic effects and to suppress the toxic side effects, the conjugate (GC-SP) was prepared by coupling between glycol-chitosan (GC) and succinyl-prednisolone (SP). The drug-release properties of GC-SP were examined and analyzed kinetically. The plasma concentration-time profiles of GC-SP and released PD were investigated after i.v. injection to normal rats, and their pharmacokinetic profiles were analyzed. PD was stable and released gradually (ca. 1%/h) from GC-SP at physiological pH, while PD was unstable at basic pH and the release from GC-SP was accelerated at basic pH. GC-SP showed good systemic retention (more than 16-fold area under the plasma concentration-time curve (AUC) as compared to PD alone), and released PD gradually in vivo. The in vivo release rate was calculated to be much faster than the in vitro rate. From these results, it is expected that GC-SP will be accumulated at inflammatory sites based on enhanced permeability and retention (EPR) effects, and release PD there effectively.

journal_name

Int J Pharm

journal_title

International journal of pharmaceutics

authors

Onishi H,Saito Y,Sasatsu M,Machida Y

doi

10.1016/j.ijpharm.2011.03.004

subject

Has Abstract

pub_date

2011-05-30 00:00:00

pages

17-22

issue

1-2

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(11)00206-7

journal_volume

410

pub_type

杂志文章

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