Micellization behavior of temperature-responsive poly (N-isopropylacrylamide) grafted dextran copolymers

Abstract

Polymeric micelles formed from amphiphilic biocompatible copolymers have received a lot of attention as drug delivery systems in recent years [1]. Pharmaceutical research on polymeric micelles has been mainly focused on block copolymers generally having hydrophilic-hydrophobic di or tri-block structures [2]. Drugs, especially lipophilic drugs, can be incorporated in the hydrophobic core of the micelles by physical entrapment techniques. Among the polymeric systems for this purpose, poly (ethylene oxide) is used the most frequently as the hydrophilic block; in contrast, the hydrophobic blocks vary widely in chemical composition range [3]. Recently, poly (N isopropylacrylamide) (PNIPAAm) was coupled into amphiphilic block copolymers where poly (ethylene glycol) [4] and poly [N -(2-hydroxypropyl) methacrylamide] [5] were used as the hydrophilic blocks. PNIPAAm exhibits a reversible phase transition in aqueous solution at about 32 ◦C, which is known to be the lower critical solution temperature (LCST). The micelles can be constructed when the temperature is raised higher than the LCST of the block copolymers containing PNIPAAm, where PNIPAAm forms the hydrophobic core. The block copolymers compose the so-called thermosensitive micelle-forming polymers. In this paper, we report the micellization behavior of PNIPAAm grafted dextran copolymers. The choice of dextran as the precursor of the graft copolymers is based on several facts. Mainly, dextrans are naturalborn hydrophilic macromolecules and have been used clinically and safely for more than 5 decades. Dextrans are biodegraded by dextranases presented in various organs in the human body, including the lower part of the gastrointestinal tract [6]. Thus dextrans may be used potentially as drug carriers for colon-specific delivery. Dextran-graft-PNIPAAm copolymers were prepared and characterized in this laboratory [7]. The phase transition temperature of the graft copolymers was determined by differential scanning calorimetry analysis using a Perkin-Elmer Pyris 1 instrument with the heating rate of 3 and 5 ◦C/min, respectively. The sample