Enhancement of the Bioavailability of Other Oral Drugs

The bioavailability and the drug action of a number of other drugs after oral administration also was improved considerably by binding to nanoparticles. The drugs showing an improved oral delivery with nanoparticles including vincamine [82], lipiodol [362], hydrocortisone [363], avarol [65], the anti-HIV drug azidothymidine, AZT [350, 351], the HIV 1 protease inhibitor CGP 57813 [156, 364], the peptide salmon calcitonin [365], and plasmid DNA, pCMV/6-gal [366] as well as pCMVArah2 [367]. With indomethacin binding to nanoparticles did not result in an improved bioavailability after oral administration but rather in a reduction in side effects, and a prolonged action was observed [368, 369]. The most interesting results were those with avarol, where a nine-fold increase in bioavailability was obtained [65], and those with salmon calcitonin and plasmid DNA. Peptides as well as naked DNA are generally rapidly degraded in the gastrointestinal tract and they are poorly adsorbed.

Oral administration of salmon calcitonin bound to poly(N-isopropyl acrylamide) nanoparticles yielded a high hypocalcemic effect. The observed pronounced absorption enhancement by the nanoparticles probably resulted from both bioadhesion to the gastrointestinal mucosa and increased stability in the gastrointestinal tract [365]. Five days after a single oral dose of plasmid DNA, pCMV/6-gal bound to fumaric acid-co-sebacic acid-polyanhydride nanoparticles was able to transfect cells in areas containing Peyer's patches [366]. Most of the transfected cells were located in the muscularis mucosae and adventita below these patches. Oral administration of pCMVArah2 com-plexed with chitosan to form nanoparticles resulted in transduced gene expression in the intestinal epithelium [367]. Mice receiving these nanoparticles produced secretory IgA and serum IgG2a. These results demonstrate that oral allergen-gene immunization with chitosan-DNA nanoparti-cles is effective in modulating murine anaphylactic responses and may be useful for treating food allergies.

The bioavailabiltiy after oral administration of drugs bound to nanoparticles may be further enhanced by the alteration of the surface properties [280]. Especially the coupling of tomato lectin seems to promising in promoting gastrointestinal uptake using nanoparticles [370].

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Allergic To Everything

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