Bioadhesive delivery systems bioadhesion testing

The most potent mucosal adjuvants have been shown to be the toxins derived from Vibrio cholerae or Escherichia coli, which should not be surprising since these organisms invade the body through the GI tract. Obviously too toxic for human use because they are the source of cholera or diarrhoea, heat labile enterotoxins have been tested in mice and shown to be potent adjuvants for orally or nasally administered influenza vaccine. The potency of heat-labile enterotoxin mutants may also be enhanced by formulation into bioadhesive particulate delivery systems, and this is an area under current exploration. 

Crystalline cellulose, hydroxypropyl cellulose, and Carbopol 934 have been studied in combination with lyophilized insulin as bioadhesive powder dosage forms for nasal delivery. Each formulation tested resulted in an decrease in plasma glucose level after nasal administration in dog and rabbit models. The most effective formulation, crystalline cellulose blended with insulin, decreased the plasma glucose level to 49% of the control value. In ternary systems the lyophilized Carbopol 934 and insulin blend with crystalline cellulose powder has been the most effective, leading to a hypoglycemia on the order of one-third of the effect obtained after intravenous injection of the same dose of insulin. The plasma glucose levels obtained in the volunteers after administration of the insulin-Carbopol-crystalline cellulose powder formulation were quite variable [38],... 

One of the problems ofbuccal delivery is that the surface of the mucous membrane is constantly washed by a stream of saliva, which will exclude a major part of the drug firom absorption and also reduce administration time. Increased residence time can be obtained by using a bioadhesive delivery system (Harris and Robinson, 1990), and such a system has been tested with insulin. A double-layered patch wi an adhesive peripheral layer that stuck to the oral mucosa for 6hr and a core consisting of insulin, sodium glycocholate, and cocoa butter was administered to dogs (Ishida etal, 1981 Nagai, 1985). Bioavailability was calculated as 0.5% as compared with intramuscular administration. 

Bioadhesive chitosan microspheres of pentazocine, an opioid, for intranasal systemic delivery, significantly improved the bioavailability with sustained and controlled blood level profiles compared to intravenous and oral administration [107]. Modification of nasal microspheres through their concomitant use with adjuvants or immunomodula-tors for an additive and a synergistic effect, and through the mannosylation of chitosan for receptor mediated targeting antigen-presenting cells was also tested [8]. 

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