Oral Delivery

The basics for the employment of nanoparticles as oral drug delivery systems were discussed in Section 6.3 and are covered in a fundamental review [277]. Following, the oral delivery of a number of drugs is described.

7.5.1. Insulin

The oral delivery of the peptide insulin is a very important and yet unresolved issue in medicine since by this route of administration the presently necessary frequent injections can be avoided. Insulin is rapidly degraded in the gastrointestinal drug and therefore cannot be given in conventional oral dosage forms. Insulin can be encapsulated into poly(isobutyl cyanoacrylate) nanocapsules particles by the interfacial polymerization method described in Section 4.2 [101-103, 358-361]. The oral administration of these nanoparticles decreased glycemia in diabetic rats fasted overnight before dosing by 50-60% [103]. This effect lasted up to 20 days. Nonencapsulated insulin had no effect. In fed diabetic rats the nanoparticles yielded a 25% reduction in blood glucose levels only at high doses. Administration to different locations in the intestine exhibited a dependence of the glycemia on the administration sites leading to 65% glycemia after administration into the ileum, 59% for administration into stomach, 52% into duodenum and jejunum, and 34% into colon [358]. Peak blood levels amounted to about 15 to 20% of the administered dose give parenterally [359]. In vitro investigations showed that the insulin is not chemically altered during nanoen-capsulation [110]. The encapsulation into the nanoparticle process appears to protect the insulin against gastric degradations by enzymes. The interaction of nanoencapsulated insulin with insulin receptors in vitro was similar to that of native insulin regarding binding, negative cooperativity, and autophosphorylation [360].

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