CPVA Grafted Poly(sodium 4-styrene sulfonate) and Studies on its Colon Specific for Chronotherapy of Nocturnal Asthma

Abstract

The paper attempted to develop a colon specific drug delivery system using CPVA grafted poly (sodium 4-styrene sulfonate)(SSS), namely CPVA-g-PSSS microsphere, loaded with theophylline (TP) for chronotherapy of nocturnal asthma. The grafted CPVA-g-PSSS microspheres were prepared by surface-initiated graft-polymerization, and their surface charges were determined by testing Zeta potential. On this basis, the adsorption property of the grafted microspheres CPVA-g-PSSS for theophylline, namely drug loading ability, was mainly investigated, and the adsorption mechanism was explored. The in vitro release behavior of the drug-loaded microspheres was also examined at different pH value and in simulated gastrointestinal fluids. The experiments show the CPVA-g-PSSS microspheres exhibit strong adsorption ability (38.5 mg/g) for TP by driving of electrostatic interaction in an acidic medium. The in vitro release behavior of the drug-loaded microspheres is highly pH-sensitive. The in vitro release in simulated gastrointestinal (GI) fluid reveals that drug does not release in the stimulated gastric fluid (pH 1), while in the simulated colonic fluid (pH 7.4), a burst release phenomenon occurs, and 52% TP is released in one hour. An excellent colon-specific drug delivery system is developed to realize a lag time of drug release in 6 h runtime of upper gastrointestinal tract, which should be consistent with the demands of chronotherapy of nocturnal asthma.

Keywords:

• graft polymerization
• microsphere
• colon-specific drug delivery
• theophylline
• chronotherapy

Acknowledgements

We are greatful of the financial support of this research project by the Graduate Innovation Foundation of Shanxi Province (No. 20123093) and Science and Technology Development Plan (Industry) of Shanxi Province (20130321017-03).