Administration routes, macromolecular

Cheever KL, DeBord DG, Swearengin TF. 1991.4,4 -Methylenebis(2-chloroaniline) (MOCA) The effect of multiple oral administration, route and phenobarbital induction on macromolecular adduct formation in the rat. Fundam AppI Toxicol 16(1) 71-80. 

The oral route is undoubtedly the most widely investigated alternative administration route however, it presents major concerns in the delivery of macromolecular actives. The gastrointestinal route can promote degradation in the stomach due to the acidic gastric pH. The intestine has issues arising from the presence of proteolytic enzymes and insufficient permeation toward these actives, all of which result in limited bioavailability. Therefore, other routes of delivery have been investigated and the oral mucosal route presents a convenient alternative. 

Considering patient acceptability and ease of administration, there is no doubt that oral administration is the most favored route, even if there have been reports on successful delivery of macromolecular drugs across nonperoral mucosal routes.6 7 Despite such advantages in oral administration, various barriers are encountered in the gastrointestinal (GI) tract that should be surmounted in order to gain sufficient bioavailability of... 

Nasal administration. Apart from parenteral administration, controlled release dosage forms based upon the microsphere concept should have application to other routes of administration. Microspheres in the form of pellets have been used to deliver drugs to the gastrointestinal tract and other examples include the administration of microspheres to the eye and topically to the lungs. In recent studies Ilium (20) has employed microspheres as possible controlled release formulations for nasal application. Such studies have relevance to the delivery of novel macromolecular compounds such as peptides and proteins. 

In conclusion, the macromolecular properties of polymers and their interactions with cell surfaces result in a specific pharmacokinetic behaviour of polymers. The routes of parenteral administration are far from being equivalent, e.g. the intraperi-toneal application often used cannot substitute the intravenous administration. Molecular parameters of the polymer circulating in the coitral compartment are changed in time not necessarily by a direct biological modification of the polymer but as a consequence of a selective processing of different fractions. The intracellular accumulation in secondary lysosomes is the only proven mode of persistence of a soluble polymer in tissues. Variations in the chemical structure of the polymer may result in a different pattern of polymer distribution in the body as a consequence of a different rate of cellular accumulation. 

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