Pharmaceutical Research

, Volume 11, Issue 9, pp 1270–1277

Preparation and Characterization of Novel Poly(methylidene Malonate 2.1.2.)-Made Nanoparticles

Authors

  • François Lescure
    • Laboratoires UPSALaboratoire de Recherche Galénique
  • Christine Seguin
    • Laboratoires UPSALaboratoire de Recherche Galénique
  • Pascal Breton
    • Laboratoires UPSALaboratoire de Recherche Galénique
  • Philippe Bourrinet
    • Laboratoires UPSALaboratoire de Recherche Galénique
  • Didier Roy
    • Laboratoires UPSALaboratoire de Recherche Galénique
  • Patrick Couvreur
    • Laboratoire de Pharmacie Galénique et de BiopharmacieUniversité
Article

DOI: 10.1023/A:1018986226557

Cite this article as:
Lescure, F., Seguin, C., Breton, P. et al. Pharm Res (1994) 11: 1270. doi:10.1023/A:1018986226557

Abstract

Poly(methylidene malonate 2.1.2.) (PMM 2.1.2.) nanoparticles were prepared 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 biodegradability 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 side chains indicated that the polymers were susceptible to hydrolysis when incubated in basic pH or in rat plasma. A secondary degradation pathway, yielding formaldehyde through a reverse Knoevenagel’s reaction, was minimal. Cytotoxicity studies of this new vector, in vitro, against L929 fibroblast cells demonstrated that PMM 2.1.2. nanoparticles were better tolerated than other poly(alkylcyanoacrylate) (PACA) carriers. Pharmacokinetic studies were also carried out to observe the fate of 14C-labelled PMM 2.1.2. nanoparticles after intravenous administration to rats. Forty eight hour post-injection, more than 80% of the radioactivity was recovered in urine and faeces. The body distribution of the polymer was estimated by measuring the radioactivity associated with liver, spleen, lung and kidneys. Five minutes after injection, a maximum of 24 ± 2% of the total radioactivity was detected in the liver and less than 0.4% in the spleen. The liver-associated radioactivity decreased according to a biphasic profile and less than 8% of the total radioactivity remained after 6 days.

drug targeting polymeric drug carrier nanoparticle polymerization biodegradation pharmacokinetics

Copyright information

© Plenum Publishing Corporation 1994