PREPARATION AND CHARACTERIZATION OF POLYETHYL-2-CYANOACRYLATE NANOCAPSULES CONTAINING ANTIEPILEPTIC DRUGS

Biocompatible and biodegradable colloidal drug delivery systems can be obtained by means of in situ polymerization of alkylcyanoacrylate. In particular, nanocapsules of polyethylcyanoacrylate (PECA) were prepar ed by adding the monomer to an organic phase, consisting of Miglyol 81 2(R) and an organic solvent (ethanol, acetone or acetonitrile), and su bsequently mixing the organic phase with an aqueous phase containing P luronic F68(R) at different concentrations. The possible mechanism of formation and the influence of preparation conditions on the quality o f nanocapsule formulations were investigated by freeze-fracture electr on microscopy and laser light scattering using both the inverse Laplac e transform and the standard cumulant analysis for data fitting. High- quality nanocapsule systems were obtained using an aprotic fully water -miscible organic solvent such as acetone. The presence of ethanol led to the formation of both nanospheres and nanocapsules. The concentrat ions of nonionic surfactant in the aqueous phase of monomer in the org anic phase did not influence the kind of colloidal suspension obtained . The oil simply plays the role of monomer support. The diameter of PE CA nanoparticles (nanospheres and nanocapsules) ranged from 100 to 400 nm. Three antiepileptic drugs (Ethosuximide, 5,5-diphenyl hydantoin a nd carbamazepine) were entrapped in PECA nanocapsules. The loading cap acity of PECA nanocapsules, prepared using acetone as organic solvent, varied from 1% to 11% (drug/dried material) as a function of the solu bility (affinity) of the different drugs with the oil core. This param eter also influenced the release from PECA nanocapsules, which was slo wer for drugs with a higher affinity for Miglyol 812. By encapsulating the three antiepileptic drugs in the PECA nanocapsules, it was possib le to achieve controlled drug release. The mechanism of drug release f rom PEGA nanocapsules was mainly diffusion from the oil core through t he intact polymer barrier.