Copolymers, controlled drug release system

Micellization of polydiene copolymers was examined by Petrak and co-workers [ 165] in the case of PEO-PI-PEO for the development of controlled drug release systems. This interest in biomedical applications was also the starting point for extensive studies on micellar systems obtained with PEO-poly(amino acid) [166, 167], PEO-polyesters block copolymers [168, 169] and PEO-poly (ethylacrylate) [170]. PEO-poly(methylidene malonate), also designated by PEO-PMM 212, of the following structure were developed in our group ... 

Polymeric micelle systems (PMS) are made by the self-assembly of amphiphilic block copolymers in an aqueous enviromnent. The important features of PMS are drug solubilization, controlled drug release, and drug targeting [26]. This chapter focuses and discusses the current scenario of natural biodegradable polymeric-based nanoblends for protein and gene delivery with a special emphasis on the pharmaceutical and biomedical approaches. 

Diblock copolymers were synthesised by two stepwise anionic polymerisation methods. One method produced diblock copolymer plus 30% of poly(2-vinylpyridine) homopolymer. The copolymers were dissolved in O.IM hydrochloric acid. When the pH was increased by the dropwise addition of 0.1 M sodium hydroxide, micelles with well-defined hydrodynamic diameters formed spontaneously at around pH 5. Further basification produced stable micelle structures and reacidification produced the mirror image of this titration curve. Blue swirls were observed when sodium hydroxide was added at pH4 or pH5. The micelle sizes were measured by quasielastic light scattering. It is shown that (1) it is possible to control micelUsation by pH and (2) formation of well-behaved micelles of variable hydrodynamic diameter is possible by titration of different ratios and different total polymer concentrations of poly(2-vinylpyridine/poly(2-vinylpyridine-block-PEO). Relevance to drug release systems that can remain intact and circulate for long periods within the vascular system is suggested. 17 refs. 

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