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

Correlating gastric emptying of amphotericin B and paracetamol solid lipid nanoparticles with changes in particle surface chemistry

Oral delivery of pharmaceuticals requires that they retain their physical and chemical attributes during transit within the gastrointestinal (GI) tract, for the manifestation of desired therapeutic profiles. Solid lipid nanoparticles (SLNs) are used as carriers to improve the absorption of hydrophobic drugs. In this study, we examine the stability of amphotericin B (AmB) and paracetamol (PAR) SLNs in simulated GI fluids during gastric emptying. On contact with the simulated fluids, the particles increased in size due to ingress of the dissolution media into the particles. Simulated gastric emptying revealed that the formulations had mean sizes <350 nm and neutral surface charges, both of which are optimal for intestinal absorption of SLNs. There was ingress of the fluids into the SLNs, followed by diffusion of the dissolved drug, whose rate depended on the solubility of the loaded-drug in the particular medium. Time-of-flight secondary ion mass spectrometry analyses indicated that drug loading followed the core-shell model and that the AmB SLNs have a more drug-enriched core than the PAR SLNs do. The AmB SLNs are therefore a very suitable carrier of AmB for oral delivery. The stability of the SLNs in the simulated GI media indicates their suitability for oral delivery

Nanotechnology as a promising strategy for alternative routes of insulin delivery

International audienceSince its discovery, insulin has been used as highly specific and effective therapeutic protein to treat type 1 diabetes and later was associated to oral antidiabetic agents in the treatment of type 2 diabetes. Generally, insulin is administered parenterally. Although this route is successful, it still has several limitations, such as discomfort, pain, lipodystrophy at the injection sites and peripheral hyperinsulinemia, which may be the cause of side effects and some complications. Thus, alternative routes of administration have been developed, namely, those based on nanotechnologies. Nanoparticles, made of synthetic or natural materials, have been shown to successfully overcome the inherent barriers for insulin stability, degradation, and uptake across the gastrointestinal tract and other mucosal membranes. This review describes some of the many attempts made to develop alternative and more convenient routes for insulin delivery

Nanoparticulate biopolymers deliver insulin orally eliciting pharmacological response

The aim of this study was to characterize and evaluate a novel oral insulin nanoparticulate system based on alginate-dextran sulfate core, complexed with a chitosan-polyethylene glycol-albumin shell. Insulin-loaded nanospheres (25, 50, 100 IU/kg) administered orally to diabetic rats reduced glycemia in a dose dependent manner. This effect lasted over 24 h with a maximal effect after 14 h. Nanospheres increased insulin plasma level and improved glycemic response to an oral glucose overload. After 4 days oral administration (50 IU/kg/day), the metabolic status of diabetic rats improved with a reduction in water intake, urine excretion and proteinuria. FITC-insulin-loaded nanospheres administered to an isolated intestinal loop were taken up by the intestinal mucosa. They strongly adhered to villus apical enterocytes and markedly labeled Peyer's patches. It is concluded that nanospheres preserve insulin and exert an antidiabetic effect after oral administration. This is explained by a protective effect against proteolytic enzymes by the albumin coating, by the mucoadhesive properties of chitosan-polyethylene glycol, and by the possibility of chitosan reversibly altering tight junctions leading to an improved absorption of insulin. This formulation demonstrates beneficial effects on diabetic symptoms and will be of interest in the treatment of diabetes with oral insulin. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sc