PHYSICOCHEMICAL CHARACTERIZATION, PREPARATION AND PERFORMANCE OF POLY(METHYLIDENE MALONATE-2.1.2) NANOPARTICLES

The present investigation confirms that initially implemented procedur e to produce poly(methylidene malonate 2.1.2) (PMM 2.1.2) nanoparticle s (Lescure et al. Pharm Res 1994;11:1270-77) lead to products mostly c ontaining plasticizing oligomers which strongly lowered glass-transiti on temperature (T-g), dramatically reduced nanoparticle consistency an d rendered them too sensitive to solubilization when diluted in an aqu eous medium. From MALDI-TOF spectroscopy analysis, performed on intact colloids, emerged some structural information about these oligomeric species which could result from an intramolecular cyclization mechanis m occurring soon in the course of the polymerization process. Thus, wi th the objective of overcoming these drawbacks, this contribution deal s with the variations of manufacturing specifications such as pH and m agnetic stirring speed to try and modulate molecular weight (M-w) of n anoparticle constituents and reduce oligomer concentration. Although t he analyses performed on these new nanoparticles were rather encouragi ng, the colloid formation yield became so low that it required the dev elopement of other methodologies, excluding a previous emulsion step, and allowing a controlled production of PMM 2.1.2-made nanoparticles h aving better physico-chemical characteristics while keeping good pharm aceutical capabilities. (C) 1998 Published by Elsevier Science Ltd. Al l rights reserved.