Oral Insulin

Oral insulin is an exciting area of research and development in the field of diabetology. This brief review covers the various approaches used in the development of oral insulin, and highlights some of the recent data related to novel oral insulin preparation

Atorvastatin calcium loaded chitosan nanoparticles: in vitro evaluation and in vivo pharmacokinetic studies in rabbits

In this study, we prepared atorvastatin calcium (AVST) loaded chitosan nanoparticles to improve the oral bioavailability of the drug. Nanoparticles were prepared by solvent evaporation technique and evaluated for its particle size, entrapment efficiency, zeta potential, in vitro release and surface morphology by scanning electron microscopy (SEM). In addition, the pharmacokinetics of AVST from the optimized formulation (FT5) was compared with marketed immediate release formulation (Atorva(r)) in rabbits. Particle size of prepared nanoparticles was ranged between 179.3 ± 7.12 to 256.8 ± 8.24 nm with a low polydispersity index (PI) value. Zeta potential study showed that the particles are stable with positive values between 13.03 ± 0.32 to 46.90 ± 0.49 mV. FT-IR studies confirmed the absence of incompatibility of AVST with excipient used in the formulations. In vitro release study showed that the drug release was sustained for 48 h. Results of pharmacokinetics study showed significant changes in the pharmacokinetic parameter (2.2 fold increase in AUC) of the optimized formulation as compared to marketed formulation (Atorva(r)). Thus, the developed nanoparticles evidenced the improvement of oral bioavailability of AVST in rabbit model.</p

Influence of repeated administration of bombesin on rat pancreatic secretion

International audienceTo study the effects of chronic bombesin on pancreatic growth and secretion, rats were injected subcutaneously, 3 times daily for 4 days with either saline or bombesin (10 micrograms/kg). Bombesin significantly increased the pancreatic weight and content in protein and RNA but not in DNA. The ratios of the three former parameters to DNA increased, suggesting cellular hypertrophy. The pancreatic content in enzymes was also elevated, especially for chymotrypsin and to a lesser degree for amylase. However, the volume of pancreatic secretion and the output of enzymes in response to CCK under a continuous infusion of secretin remained unchanged. The in vitro secretory response to caerulein and bombesin was reduced for amylase and lipase. It is concluded that chronic bombesin exerts a trophic action on the rat pancreas but decreases the sensitivity of each cell to hormonal stimulation

Effect of chronic bombesin on pancreatic size, composition and secretory function in the rat.

Bombesin administered subcutaneously to rats, three times daily for four days, induces pancreatic growth at a dose of 10 micrograms/kg. Growth was characterised by an increased pancreatic weight and content in protein and RNA, accompanied by cellular hypertrophy. Chronic bombesin also enhanced the pancreatic content in chymotrypsin and to a lesser degree its contents in amylase and lipase. The volume of the secretion and the output of enzymes in response to CCK under an infusion of secretin, however, remained unchanged although the functional capacity of individual cells to secret amylase and lipase was reduced. It is concluded that chronic bombesin exerts a trophic action on the rat pancreas but decreases the sensitivity of each cell to hormonal stimulation

STAPLERS IN GASTROINTESTINAL SURGERY - CORROSION OF ALLOY WITH RELEASE

Meeting Abstrac

Gastrin modulation of pancreatic growth

International audienceGastrin has been proposed as a trophic factor for the pancreas. Extensive small-bowel resection increased transiently plasma gastrin levels in the rat and produced pancreatic growth. This growth was characterized by an increased pancreatic weight, protein and DNA content, and the occurrence of mitotic figures in acinar cells. in order to determine if gastrin is implicated in pancreatic hyperplasia, we induced endogenous variations of gastrin 3 weeks before small-bowel resection or transection. Hypogastrinernia was produced by antrectomy and hypergastrinemia by vagotomy plus pyloroplasty. Pyloroplasty alone was without any effect. All gastric operations alone enhanced though not significantly the weight of the pancreas and its content in protein and DNA. When performed before intestinal resection, they did not modify the hyperplasic response of the pancreas to the resection. Our findings do not support the views that antral gastrin exerts a trophic action on the rat pancreas and that gastrin is implicated in postresectional hyperplasia of the gland

Alginate/Chitosan Nanoparticles are Effective for Oral Insulin Delivery

Abstract Purpose To evaluate the pharmacological activity of insulin-loaded alginate/chitosan nanoparticles following oral dosage in diabetic rats. Methods Nanoparticles were prepared by ionotropic pre-gelation of an alginate core followed by chitosan polyelectrolyte complexation. In vivo activity was evaluated by measuring the decrease in blood glucose concentrations in streptozotocin induced, diabetic rats after oral administration and flourescein (FITC)-labelled insulin tracked by confocal microscopy. Results Nanoparticles were negatively charged and had a mean size of 750 nm, suitable for uptake within the gastrointestinal tract due to their nanosize range and mucoadhesive properties. The insulin association efficiency was over 70% and insulin was released in a pH-dependent manner under simulated gastrointestinal conditions. Orally delivered nanoparticles lowered basal serum glucose levels by more than 40% with 50 and 100 IU/kg doses sustaining hypoglycemia for over 18 h. Pharmacological availability was 6.8 and 3.4% for the 50 and 100 IU/kg doses respectively, a significant increase over 1.6%, determined for oral insulin alone in solution and over other related studies at the same dose levels. Confocal microscopic examinations of FITC-labelled insulin nanoparticles showed clear adhesion to rat intestinal epithelium, and internalization of insulin within the intestinal mucosa. Conclusion The results indicate that the encapsulation of insulin into mucoadhesive nanoparticles was a key factor in the improvement of its oral absorption and oral bioactivity

Small bowel bypass prevents the trophic action of cholecystokinin on the rat pancreas

International audienceThe effect of a chronic administration of cholecystokinin (CCK) on the rat pancreas has been studied in rats subjected to a 90% jejunoileal bypass or an intestinal transection (controls). Jejunoileal bypass, when compared to transection, did not modify the size of the pancreas but decreased its enzyme content, especially for amylase, and reduced the number of zymogen granules. These structural and biochemical changes were maintained when bypassed animals were treated three times daily and for six days with cholecystokinin (20 Ivy Dog Units (IDU)/kg). In contrast, CCK treatment in transected animals induced growth of the pancreas due to cellular hypertrophy and hyperplasia; pancreatic enzyme content, especially for chymotrypsin, and the population of zymogen granules in acinar cells were also enhanced. It is concluded that jejunoileal bypass prevents the trophic action of chronic CCK on the pancreas

Combined effect of chronic bombesin and secretin or cholecystokinin on the rat pancreas

International audienceThis work investigates the pancreatico-trophic action of bombesin, a peptide stimulating pancreatic secretion in vivo and in vitro and examines whether this effect is altered by CCK or secretin. Rats were injected three times daily for 5 days either with saline, bombesin (1 or 10 μg/kg), CCK (20 I.D.U. kg), secretin (20 C.U./kg) or a combination of bombesin and CCK or secretin. Bombesin alone induced growth of the pancreas beginning with the dose of 10 μg/kg. This growth was characterized by an increase of pancreatic weight, its protein, RNA and enzyme content, but not of its DNA content. The ratios of the three former parameters to DNA increased, suggesting cellular hypertrophy. Cholecystokinin alone exhibited a similar trophic action on the pancreas as bombesin. Secretin alone had no effect on pancreatic size and composition. Cholecystokinin and secretin did not modify the pancreatico-trophic response of bombesin. These findings suggest that bombesin, administered for 5 days in the rat, induces pancreatic growth due to cellular hypertrophy. Cholecystokinin has the same effect. However the mode of action, at the cellular level, of bombesin appears to be different from that of cholecystokinin