International Journal of Pharmaceutics 183 (1999) 63 – 66 Short communication Physico-chemical characterization of insulin-loaded poly(isobutylcyanoacrylate) nanocapsules obtained by interfacial polymerization Malam Aboubakar, Francis Puisieux, Patrick Couvreur, Christine Vauthier * URA CNRS 1218, Uniersite ´ de Paris XI, Faculte ´ de Pharmacie, 5 rue J.B. Cle ´ment, 92 296 Chatenay Malabry Cedex, France Received 18 December 1998; accepted 14 January 1999 Abstract Insulin could be encapsulated very efficiently in oily containing poly(isobutylcyanoacrylate) nanocapsules obtained by interfacial polymerization. In addition, these nanocapsules showed unexpected biological activity after intragastric administration. The hypoglycemic effect was characterized by a lag time period of 2 days and a prolonged effect over a period of 20 days. To explain, the high encapsulation rate of insulin achieved in these nanocapsules and the biological effect, this work was focused on the characterization of the nanocapsules and on the study of the mechanism of nanocapsule formation. Results showed that insulin was found unmodified during the nanoencapsula- tion process. This was due to the large amount of ethanol used in the preparation of the nanocapsules that initiated the polymerization of isobutylcyanoacrylate preserving the peptide from a reaction with the monomer. Results also showed that insulin was located inside the core of the nanocapsules and not simply adsorbed onto their surface. © 1999 Elsevier Science B.V. All rights reserved. Keywords: Insulin; Nanocapsules; Poly(isobutylcyanoacrylate); Isobutylcyanoacrylate; Polymerization initiation Intragastric administration of insulin-loaded poly(isobutylcyanoacrylate) nanocapsules induced a reduction of the glycemia to normal level in streptozotocin diabetic rats (Aprahamian et al., 1987; Damge ´ et al., 1988, 1990) and in alloxan induced diabetic dogs (Damge ´ et al., 1995). The hypoglycemic effect was characterized by surpris- ing events including a lag time period of 2 days and a prolonged effect over a period of 20 days. Insulin is a very hydrosoluble peptide and should * Corresponding author. Fax +33-1-46-61-93-34. E-mail address: christine.vauthier@cep.u-psud.fr (C. Vau- thier) 0378-5173/99/$ - see front matter © 1999 Elsevier Science B.V. All rights reserved. PII:S0378-5173(99)00045-9