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

Abstract

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 ef ciency 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 peptideloaded 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 signi cantly 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.

Methods for the Preparation and Manufacture of Polymeric Nanoparticles

“…They must be desalted before they can be administered in vivo by the intravenous route. In another example, water containing nanocapsules dispersed in oil as provided from the synthesis can be administered by the oral route (205). However, they need to be cleaned and transferred in an aqueous medium before they will suit prerequisites for an administration by the intravenous route (20).…”

Nanotechnology: Intelligent Design to Treat Complex Disease

“…Thus, protection of the drug against degradation may differ according to the type of nanoparticles and depending on the release profile of the peptide from the nanodevice (304,308,309,319,321,322). For example, poly(alkylcyanoacrylate) nanocapsules resisted well in the gastric fluid retaining the encapsulated insulin inside the nanocapsules.…”

Polymeric Nanocapsules for Drug Delivery

“…The activity of insulin-loaded PAC nanocapsules was evaluated after subcutaneous administration, showing a reduction in blood glucose in diabetic rats, which was delayed by the nanoencapsulation (Watnasirichaikul et al, 2002). The formulation of insulin-loaded nanocapsules dispersed in a water-in-oil microemulsion showed a signifi cant increase in the oral bioavailability of insulin in diabetic rats (Watnasirichaikul et al, 2002).…”