In-vitro release and oral bioactivity of insulin in diabetic rats using nanocapsules dispersed in biocompatible microemulsion

This study evaluated the potential of poly(iso-butyl cyanoacrylate) (PBCA) nanocapsules dispersed in a biocompatible microemulsion to facilitate the absorption of insulin following intragastric administration to diabetic rats. Insulin-loaded PBCA nanocapsules were prepared in-situ in a biocompatible water-in-oil microemulsion by interfacial polymerisation. The microemulsion consisted of a mixture of medium-chain mono-, di- and tri-glycerides as the oil component, polysorbate 80 and sorbitan mono-oleate as surfactants and an aqueous solution of insulin. Resulting nanocapsules were approximately 200 nm in diameter and demonstrated a high efficiency of insulin entrapment (> 80%). In-vitro release studies showed that PBCA nanocapsules could suppress insulin release in acidic media and that release at near neutral conditions could be manipulated by varying the amount of monomer used for polymerisation. Subcutaneous administration of insulin-loaded nanocapsules to diabetic rats demonstrated that the bioactivity of insulin was largely retained following this method of preparing peptide-loaded nanocapsules and that the pharmacodynamic response was dependent on the amount of monomer used for polymerisation. The intragastric administration of insulin-loaded nanocapsules dispersed in the biocompatible microemulsion resulted in a significantly greater reduction in blood glucose levels of diabetic rats than an aqueous insulin solution or insulin formulated in the same microemulsion. This study demonstrates that the formulation of peptides within PBCA nanocapsules that are administered dispersed in a microemulsion can facilitate the oral absorption of encapsulated peptide. Such a system can be prepared in-situ by the interfacial polymerisation of a water-in-oil biocompatible microemulsion

Effects of formulation variables on characteristics of poly(ethylcyanoacrylate) nanocapsules prepared from w/o microemulsions

The effect of several formulation variables on some of the physico-chemical characteristics of poly (ethyl cyanoacrylate) (PECA) nanocapsules prepared by the interfacial polymerisation of biocompatible water-in-oil microemulsions was investigated. In all cases, yields were high (>90%) and the polydispersity in size of nanocapsules was narrow. The molecular weight of the nanocapsules formed was influenced by the pH of the aqueous component of the microemulsion, increasing with increasing pH. The size of the nanocapsules formed (ranging from around 130 to 180 nm) was a function of the ratio of the mass of monomer used to the water weight fraction of the microemulsion, increasing as this ratio was increased. This is due to the formation of a thicker polymer wall resulting from the increased mass of monomer available per unit interfacial area as this ratio is increased. The rate of release of insulin from nanocapsules was also influenced by this ratio, in agreement with its effect on wall thickness. This study demonstrates that many pharmaceutically relevant physico-chemical properties of poly (alkyl cyanoacrylate) (PACA) nanocapsules prepared by interfacial polymerisation of microemulsions can readily be manipulated by changing either the pH of the aqueous component, the water weight fraction of the microemulsion or the mass of monomer used for polymerisation