New approach for oral administration of insulin with polyalkylcyanoacrylate nanocapsules as drug carrier

Intestinal Receptor Targeting for Peptide Delivery: an expert‘s Personal Perspective on Reasons for Failure and New Opportunities

“…There are several reports of abnormally high oral bioavailabilities of insulin (up to 22%) following incorporation within protec tive matrixes, such as nanoparticles and muco adhesive polymers [59,[149][150][151][152][153][154][155][156][157][158][159][160][161][162][163][164][165][166]. Similar results have been reported by Pan and others [68], who estimated an oral bioavailability of 14.9% for 250-400 nm chitosan nanoparticles containing insulin.…”

“…Attention switched to looking at uptake of nanoparticles that could be loaded with peptides and proteins. Initial work focused on the use of 125 Iinsulinloaded isobutylcyano acrylate (IBCA) nanoparticles [155,156]. While it was relatively easy to load these particles, it was quickly found that the majority of the insulin was physically located on or near the surface of the nanoparticles and was rapidly degraded upon incubation with smallintestinal washout fluid.…”

“…In this regard, the majority of studies reported above did not optimize the formulation of insulin to ensure that it was presented in a monomeric form in the intestine and, furthermore, all studies used either standard human or bovine insulin, rather than an insulin preparation such as Lispro or Insulin Aspart, which would have presented as a monomer in the intestine. Proteolytic pro tection of insulin could be afforded either by chemical modification of the enzymatic sites for cleavage, which may explain the high levels of uptake seen by several researchers [177,187,189,190] or, alternatively, it could be physical protection, such as seen in liposomal preparations [178][179][180][181][182][183][184][185] or nanoparticulate structures [149][150][151][152][153][154][155][156][157][158][159][160][161][162][163][164]. These would not require additional targeting, but rather the monomeric form of insulin to be present for maximal receptor binding.…”

Insulin-S.O (sodium oleate) complex-loaded PLGA nanoparticles: Formulation, characterization andin vivoevaluation

“…Wistar rats (body weight 180-220 g) were induced into diabetes by an injection of STZ (65 mg/kg body weight) in a 10 mM citrate buffer at pH 4.5, as previously described (Damgé et al 1988). The concentration of the STZ was 13 mg/ml.…”

Novel alginate gel microspheres produced by impinging aerosols for oral delivery of proteins

“…Since protein modifications do not prevent exposure of the macromolecule to hydrolytic and proteolytic environments in the intestinal lumen, microencapsulation has been widely investigated to protect proteins and present high concentrations of active compounds at absorption surfaces, thereby enhancing the prospects for transport across the epithelium. Encapsulated oral protein formulations have encompassed a wide range of polymers and carrier systems including liposomes, pH responsive hydrogels and microemulsions (Damge et al, 1988;Masuda et al, 2002;Toorisaka et al, 2003;Vauthier et al, 2003;Morishita et al, 2006). Alginate polysaccharides in particular have featured strongly in such studies because of the polymer's processability by completely water-based methods, a mild cross-linking reaction based on divalent metal ions, favourable biocompatibility and generally regarded as safe status as a food additive (Tonnesen and Karlsen, 2002).…”