ALKYLCYANOACRYLATE DRUG CARRIERS .2. CYTOTOXICITY OF CYANOACRYLATE NANOPARTICLES WITH DIFFERENT ALKYL CHAIN-LENGTH

The cytotoxicity of four types of alkylcyanoacrylate particles was evaluated in L929 fibroblast cell cultures. The results revealed the ethyl- and isobutyl-derivatives to be the most toxic, the methyl-derivative to be of intermediate toxicity and the isohexyl-cyanoacrylate particles to have the lowest toxicity. The toxic effect was found to be correlated with the velocity of polymer degradation and the rate of release of the degradation products. The mechanism proposed to account for the observed cytotoxicity consists of the degradation of particles in the culture medium and/or of particles adhering to or in close proximity with the cell membrane. A contribution due to the internalization of particles by cells appeared to be negligible, if any, in the cytotoxicity of nanoparticles. Acute toxicity can be avoided by employing low doses of particles consisting of a slowly degrading cyanoacrylate polymer. This aspect is of interest in the development of a colloidal carrier for the chronic delivery of drugs. The use of such systems does not involve problems as a result of long-term toxicity during chronic treatments and the burden placed upon the body by overloading with polymeric drug carriers that undergo degradation more slowly, such as poly(hydroxybutyric acid) and poly(lactic acid).