PREPARATION AND CHARACTERIZATION OF NOVEL POLY(METHYLIDENE MALONATE 2.1.2.)-MADE NANOPARTICLES

Poly(methylidene malonate 2.1.2.) (PMM 2.1.2.) nanoparticles were prep ared in phosphate buffer through emulsion polymerization of monomeric units; the kinetics of the reaction was monitored by spectrophotometry at 400 nm. Average nanoparticle sizes, molecular weights, and biodegr adability of this potential drug carrier were determined under various conditions. As previously demonstrated for other similar monomers, i. e. IHCA or IBCA, pH influenced the physico-chemical characteristics of the nanoparticles obtained. Ethanol release from the ester-bearing si de chains indicated that the polymers were susceptible to hydrolysis w hen incubated in basic pH or in rat plasma. A secondary degradation pa thway, yielding formaldehyde through a reverse Knoevenagel's reaction, was minimal. Cytotoxicity studies of this new vector, in vitro, again st L929 fibroblast cells demonstrated that PMM 2.1.2. nanoparticles we re better tolerated than other poly(alkylcyanoacrylate) (PACA) carrier s. Pharmacokinetic studies were also carried out to observe the fate o f C-14-labelled PMM 2.1.2, nanoparticles after intravenous administrat ion to rats. Forty eight hour post-injection, more than 80% of the rad ioactivity was recovered in urine and faeces. The body distribution of the polymer was estimated by measuring the radioactivity associated w ith liver, spleen, lung and kidneys. Five minutes after injection, a m aximum of 24 +/- 2% of the total radioactivity was detected in the liv er and less than 0.4% in the spleen. The liver-associated radioactivit y decreased according to a biphasic profile and less than 8% of the to tal radioactivity remained after 6 days.