Preparation of biodegradable insulin nanocapsules from biocompatible microemulsions

被引:148
作者
Watnasirichaikul, S [1 ]
Davies, NM [1 ]
Rades, T [1 ]
Tucker, IG [1 ]
机构
[1] Univ Otago, Sch Pharm, Formulat & Drug Delivery Grp, Dunedin, New Zealand
关键词
nanocapsules; microemulsions; interfacial polymerization; insulin; peptides;
D O I
10.1023/A:1007574030674
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Purpose. 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.
引用
收藏
页码:684 / 689
页数:6
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