Biodegradable nanocapsules containing a lipophilic immunomodulator: drug retention and tolerance towards macrophages in vitro.

Nanocapsules (250 nm diameter) were prepared from poly (D, L-lactide) containing a lipophilic immunomodulator: MDP-L-alanyl cholesterol (MTP-Chol). High encapsulation rates were obtained at 37 degrees C in culture medium or in buffers imitating phagosomes and lysosomes. The tolerance of these particles by rat alveolar macrophages in vitro was tested. A slight toxicity was observed which was the result of two factors: the capacity of the immunomodulator to stimulate the generation of nitrite oxide by the L-arginine-dependent pathway and the polymer itself. The latter toxicity seemed to be mediated by a different mechanism.