PubMed · 9848439
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E Rubinstein, N Keller. 1998. Spiramycin renaissance.. https://doi.org/10.1093/jac%2F42.5.572
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Polyvinyl alcohol (PVA) is hydrophilic and swells easily by absorbing water. Some grades of PVA, whose degree of hydrolysis is 96.0 and 97.5 mol%, showed volume expansion of 500% by swelling at 37 degrees C. This expansion was inhibited by swelling controlling agents, namely salts. Based on this unique property of PVA, a new type of controlled release system was developed. The release rate was controlled by the content of PVA and a swelling controlling agent in the core tablet, and the composition and coating level of the film. Emedastine difumarate was incorporated into the system. At the initial stage of drug release, the rate of release was determined by the permeation through the membrane - a mixture of ethylcellulose and hydroxypropyl methylcellulose. After the membrane burst by the swelling of PVA, the release rate was controlled by the PVA matrix. Release patterns of zero-order, two phase zero-order, and rapid release after lag-time were obtained with this system.
In recent years scientific and technological advancements have been made in the research and development of rate-controlled oral drug delivery systems by overcoming physiological adversities, such as short gastric residence times (GRT) and unpredictable gastric emptying times (GET). Several approaches are currently utilized in the prolongation of the GRT, including floating drug delivery systems (FDDS), also known as hydrodynamically balanced systems (HBS), swelling and expanding systems, polymeric bioadhesive systems, modified-shape systems, high-density systems, and other delayed gastric emptying devices. In this review, the current technological developments of FDDS including patented delivery systems and marketed products, and their advantages and future potential for oral controlled drug delivery are discussed.
Previous studies showed that local macrophages phagocytose nonantigenic chitin particles (1-10 micrometer polymers of N-acetyl- d -glucosamine) through mannose receptors and produce IL-12, IL-18, and TNF-alpha. These cytokines lead to the production of IFN-gamma by NK cells. To determine whether chitin could down-regulate Th2 responses, chitin was given orally (8 mg/day for 3 days before and 13 days during ragweed allergen immunization) in BALB/c and C57BL/6 mice. These ragweed-immunized mice were given ragweed intratracheally on day 11. Three days after the challenge, the immunized mice with saline (controls) showed increases in serum IgE levels and lung eosinophil numbers. The chitin treatment resulted in decreases of these events in both strains. To dissect the inhibitory mechanisms of Th2 responses, spleen cells (4 x 106 cells/ml) isolated from the ragweed-immunized mice (controls) were cultured in the presence of ragweed and/or chitin for 3 days (recall responses). Ragweed alone stimulated the production of IL-4 (0.6 ng/ml), IL-5 (20 U/ml), and IL-10 (3.2 ng/ml), but not IFN-gamma. Ragweed/chitin stimulation resulted in significant decreases of IL-4, IL-5, and IL-10 levels and the production of IFN-gamma (48 U/ml). Moreover, spleen cells isolated from the chitin-treated mice showed ragweed-stimulated IFN-gamma production (15 U/ml) and significantly lower levels of the Th2 cytokines, suggesting that the immune responses were redirected toward a Th1 response. Collectively, these results indicate that chitin-induced innate immune responses down-regulate Th2-facilitated IgE production and lung eosinophilia in the allergic mouse.