Colon Targeting

In several studies the involvement of macrophages and dendritic cells in active inflammatory bowel disease (IBD) has been indicated. An efficient manipulation of those cells might be considered as an interesting potential therapeutic pathway for IBD treatment, since it was reported that biodegradable microspheres can be sufficiently taken by macrophages and M cells [184]. Based on these results, the direct uptake of anti-inflammatory agents by macrophages, achieved with the use of microspheres, appears to have a superior immunosuppressive effect and to be more useful for the treatment of patients with IBD [185, 186]. Nanopar-ticles showed a size dependent accumulation in the inflamed tissue and were, therefore, thought to be even more promising in the treatment of this disease. They proved the ability to target the macrophages and ruptures (Fig. 14) inside the ulcerated tissue in IBD for a specific local drug delivery [187, 188]. This type of new strategy aims to selectively accumulate the drug delivery system at the site of action. Polymeric nanoparticulate carrier systems were expected to target the inflamed tissue in inflammatory bowel diseases. Since no sedimentation occurs with colloidal drug carriers, they might be less or not at all affected by the streaming due to their diffusing properties. With the anti-inflammatory model drug rolipram, the entire drug loaded nanoparticle formulations proved to be as efficient as the drug in solution in mitigating the experimental colitis. First, the inflammation activity score and myeloperoxidase activity decreased significantly after the oral administration of rolipram nanoparticles

Figure 14. Histological section across inflamed colonic tissue. The ulceration exhibits distinct immune related cell extravasion while the mucus production is highly increased in intact mucosa (black areas on the left). Reprinted with permission from [187], A. Lamprecht et al., J. Pharmacol. Exp. Ther. 299, 775 (2001). © 2001, American Society for Pharmacology and Experimental Therapeutics.

Figure 14. Histological section across inflamed colonic tissue. The ulceration exhibits distinct immune related cell extravasion while the mucus production is highly increased in intact mucosa (black areas on the left). Reprinted with permission from [187], A. Lamprecht et al., J. Pharmacol. Exp. Ther. 299, 775 (2001). © 2001, American Society for Pharmacology and Experimental Therapeutics.

or solution. When animals were kept without drug treatment the drug solution group displayed a strong relapse, whereas the nanoparticle groups maintained reduced inflammation levels. Moreover, when free drug was administered, the rolipram solution group exhibited a high adverse effect index, whereas the rolipram nanoparticle groups proved their potential to retain the drug from systemic absorption as evidenced by a significantly reduced index. An essential advantage of this strategy seems to be the direct contact of the carriers with the inflammation site which allows a much higher local drug concentration. Moreover, nanopar-ticles were found not only to accumulate in the ulceration but also to adhere distinctly to the mucus which allows an increased specificity to nonulcerated inflamed tissue since mucus production is highly increased all over the inflamed tissue.

These new delivery systems allow the desired drug to accumulate in the inflamed tissue with a relatively high efficiency including two major advantages. The drug is concentrated at its site of action, which reduces possible adverse effects and enhances the effect of the administered dose. Moreover, the sustained drug release allows pharmacological effects to be extended due to the prolonged residence time of the carrier system at the targeted inflamed area. This deposition of polymeric carrier systems in the inflamed tissues might be promising in the design of new carrier systems for the treatment of inflammatory bowel disease.

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