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The tissue distribution of water-soluble, non-biodegradable co polymers prepared from N-(2-hydroxypropyl)methacrylamide (HPMA) and N-[2-(4-hydroxyphenyl)ethyl]acrylamide (HPEA) is described, and their poten tial for use as carriers in drug delivery is discussed. Copolymers with weight- average molecular weights (Mw) of 4, 18, 75, and 90 x 103 Daltons, of low poly dispersity ( ≅Mw/Mn ≤ 1.40), were radiolabelled with 125I and administered intravenously to mice. The biodistribution of the radioiodinated copolymers was determined at 10 min, 0.5, 2, 6, 12, 24, 48, 72, and 168 h. All the copoly mers exhibited a molecular weight related clearance from the blood compart ment. Over the time course of our experiments the copolymers were found to access and be retained within different tissues of the body, in particular the skin and muscle, their rate of access and retention being governed by their molecular size (indicated here by molecular weight). No fractionation of molec ular weight occurred in vivo, as determined by Gel Permeation Chromatog raphy of extracted radioiodinated material from the mice. Comparatively little poly(HPMA/HPEA) was found associated with the liver and spleen, (organs of the mononuclear phagocyte system). Autoradiography of animal tissue sug gested that the copolymers appeared to be located in vivo in the muscle, dermis, at the interface of fat deposits (but not over the fat), hair follicles, and epider mis. The copolymers appeared not to be located intracellularly. For drug- delivery applications it is unlikely that these nonbiodegradable polymers will be of clinical use in chronic situations unless it can be categorically demon strated that the polymers are able to be completely removed from the body.

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