Preparation of biodegradable insulin nanocapsules from biocompatible microemulsions.
OBJECTIVE
To prepare poly(ethyl 2-cyanoacrylate) nanocapsules containing insulin by interfacial polymerization of spontaneously forming, biocompatible microemulsions.


METHODS
A pseudo-ternary phase diagram of a mixture of medium chain glycerides (caprylic/capric triglycerides and mono-/diglycerides), a mixture of surfactants (polysorbate 80 and sorbitan mono-oleate) and water was constructed. Polarizing light microscopy was used to identify combinations forming microemulsions. Microemulsions were characterized by conductivity and viscosity to select systems suitable for the preparation of poly(ethyl 2-cyanoacrylate) nanocapsules by interfacial polymerization. Nanocapsules were prepared by addition of 100 mg of ethyl 2-cyanoacrylate to a stirred water-in-oil microemulsion containing 1 g of water, 7.6 g of oil, and 1.4 g of surfactant. The nanocapsules formed were characterized by photon correlation spectroscopy, freeze fracture transmission and scanning electron microscopy. Insulin nanocapsules were prepared by using an aqueous solution of insulin (100 units/ml) as the dispersed phase of the microemulsion. The entrapment and the release of insulin from the nanocapsules were determined.


RESULTS
Three regions were identified in the pseudo-ternary phase diagram; a microemulsion region, a region in which liquid crystalline structures were present and a coarse emulsion region. All systems in the microemulsion region were water-in-oil dispersions. Poly(ethyl 2-cyanoacrylate) nanocapsules having a mean particle size of 150.9 nm were formed upon interfacial polymerization of the microemulsion. Nanocapsules were found to have a central cavity surrounded by a polymer wall. In excess of 80% of the insulin present in the microemulsion was encapsulated upon interfacial polymerization.


CONCLUSIONS
Interfacial polymerization of spontaneously forming water-in-oil microemulsions represents a convenient method for the preparation of poly(alkylcyanoacrylate) nanocapsules suitable for the entrapment of bioactive peptides.
Watnasirichaikul
S
S
Formulation and Drug Delivery Group, School of Pharmacy, University of Otago, Dunedin, New Zealand.
Davies
N M
NM
Rades
T
T
Tucker
I G
IG
D020341:Absorbable Implants; D001672:Biocompatible Materials; D004343:Drug Implants; D004655:Emulsions; D007328:Insulin / Q000737:chemistry*; D008854:Microscopy, Electron
D001672:Biocompatible Materials; D004343:Drug Implants; D004655:Emulsions; D007328:Insulin