A novel approach for the control of drug release rate through hydrogel membrane: I. Effect of drug immobilization on drug release rate by copolymerization method

Abstract

Precise control of drug release rate in hydrogel drug delivery systems to better mimic physiological condition is a challenging research topic in development of Advanced Drug Delivery Systems. One of the major issues with bioresponsive drug delivery systems is the excessive ‘leakage’ of drug while the system is in the ‘off’ state, which leads to shortening of the device life-time and potential overdose problem for the patient. In the present study, a new approach, based on partition effects, termed drug immobilization via copolymerization, is proposed to control the drug release rate of membrane-based drug delivery systems. In this method, a certain level of drug is pre-immobilized in the membrane through copolymerization. The immobilized drug contributes to the overall chemical potential of drug molecules in the membrane but their mobility is restricted, hence will not be released. At equilibrium, the amount of drug from donor that dissolved in the membrane is reduced due to contribution of immobilized drug, resulting in an effective reduction in partition coefficient and hence the release rate. The testing of the method by bovine serum albumin (BSA) as a model drug confirmed the controllability of the method: almost 35% reduction of the drug leakage in the ‘off-state’ was observed when 20 mg BSA was immobilized in the pH-sensitive hydrogel membrane. The mathematical model of the drug partition in the membrane was modified to describe the new partition phenomenon (mobile drug and immobilized drug in the membrane) in this study.