Preparation of Biodegradable Insulin Nanocapsules from Biocompatible Microemulsions

Purpose. To prepare poly(ethyl 2-cyanoacrylate) nanocapsulescontaining insulin by interfacial polymerization of spontaneously forming,biocompatible microemulsions.Methods. A pseudo-ternary phase diagram of a mixture of mediumchain glycerides (caprylic/capric triglycerides and mono-/diglycerides),a mixture of surfactants (polysorbate 80 and sorbitan mono-oleate) andwater was constructed. Polarizing light microscopy was used to identifycombinations forming microemulsions. Microemulsions werecharacterized by conductivity and viscosity to select systems suitable for thepreparation of poly(ethyl 2-cyanoacrylate) nanocapsules by interfacialpolymerization. Nanocapsules were prepared by addition of 100 mgof ethyl 2-cyanoacrylate to a stirred water-in-oil microemulsioncontaining 1 g of water, 7.6 g of oil, and 1.4 g of surfactant. Thenanocapsules formed were characterized by photon correlation spectroscopy,freeze fracture transmission and scanning electron microscopy. Insulinnanocapsules were prepared by using an aqueous solution of insulin(100 units/ml) as the dispersed phase of the microemulsion. Theentrapment and the release of insulin from the nanocapsules were determined.Results. Three regions were identified in the pseudo-ternary phasediagram; a microemulsion region, a region in which liquid crystallinestructures were present and a coarse emulsion region. All systems inthe microemulsion region were water-in-oil dispersions.Poly(ethyl 2-cyanoacrylate) nanocapsules having a mean particle size of 150.9 nmwere formed upon interfacial polymerization of the microemulsion.Nanocapsules were found to have a central cavity surrounded by apolymer wall. In excess of 80;pc of the insulin present in themicroemulsion was encapsulated upon interfacial polymerization.Conclusions. Interfacial polymerization of spontaneously formingwater-in-oil microemulsions represents a convenient method for thepreparation of poly(alkylcyanoacrylate) nanocapsules suitable for theentrapment of bioactive peptides.