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.
Morin
C
C
URA CNRS 1218, Laboratoire de Pharmacie Galénique et Biopharmacie, Faculté de Pharmacie, Université de Paris Sud, Chatenay-Malabry, France.
Barratt
G
G
Fessi
H
H
Devissaguet
J P
JP
Puisieux
F
F
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D002214:Capsules; D002788:Cholesterol Esters / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D005260:Female; D066298:In Vitro Techniques; D008262:Macrophage Activation / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
D000276:Adjuvants, Immunologic; D002214:Capsules; D002788:Cholesterol Esters; D011091:Polyesters; D009569:Nitric Oxide; C033616:poly(lactide); D000119:Acetylmuramyl-Alanyl-Isoglutamine; C047489:N-acetylmuramyl-alanyl-isoglutamine-alanyl-cholesterol