Physico-chemical characterization, preparation and performance of poly (methylidene malonate 2.1.2) nanoparticles.
The present investigation confirms that initially implemented procedure to produce poly(methylidene malonate 2.1.2) (PMM 2.1.2) nanoparticles (Lescure et al. Pharm Res 1994;11:1270-77) lead to products mostly containing plasticizing oligomers which strongly lowered glass-transition temperature (Tg), dramatically reduced nanoparticle consistency and rendered them too sensitive to solubilization when diluted in an aqueous 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 mechanism occurring soon in the course of the polymerization process. Thus, with the objective of overcoming these drawbacks, this contribution deals with the variations of manufacturing specifications such as pH and magnetic stirring speed to try and modulate molecular weight (MW) of nanoparticle constituents and reduce oligomer concentration. Although the analyses performed on these new nanoparticles were rather encouraging, the colloid formation yield became so low that it required the development of other methodologies, excluding a previous emulsion step, and allowing a controlled production of PMM 2.1.2-made nanoparticles having better physico-chemical characteristics while keeping good pharmaceutical capabilities.
VIRSOL, Paris, France. pbreton@club-intenet.fr
P
P
Breton
X
X
Guillon
D
D
Roy
F
F
Lescure
G
G
Riess
N
N
Bru
C
C
Roques-Carmes
D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004337:Drug Carriers; D008314:Malonates / Q000138:chemical synthesis / Q000737:chemistry*; D008970:Molecular Weight; D010316:Particle Size; D011095:Polyethylenes / Q000138:chemical synthesis / Q000737:chemistry*; D012995:Solubility; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013696:Temperature
D001672:Biocompatible Materials; D004337:Drug Carriers; D008314:Malonates; D011095:Polyethylenes; C091414:poly(methylidene malonate) 2.1.2