Polymeric Drugs and Drug Carriers

Polymeric Drugs and Drug Carriers.—The literature in this field, which includes pharmacologically active polymers, drugs covalently bound to a polymeric carrier, and drugs and enzymes absorbed onto, or encapsulated in, a polymer, has been 

Moartensson. D. Selander. I. Wickstram, and J. Ahimen, Acta Med. Scand.. 1980. 207.455. 

Benuwitz. C. Abolin, T. Tozer, J. Rosenberg. W. Rogers. S. Fond, P. Schoenfeld, and M. Humphreys. C/in. Pharmacol. Ther., 1980,27,236. 

Nakabayashi, E. Masuhara, S. Nakagawa, and S. Koshikawa, Kobunshi Ronbunshu, 1979, 36, 279. 

Several authors have presented in vitro studies of release. Amongst these a group of six papers by Yoshida and co-workers, together with others by Heller et a/.  

Dental Applicaticms.— The literature in this field is extensive. Regular specialist reviews are however compiled by Braden who has also summarized the wide 

146 Polymeric Drugs , ed. L. G. Donamura and O. Vogel, Academic Press, New York, 1978 (see also L. G. Donamura, Chapter 1 in Progress in Polymer Science , ed. A. D. Jenkins, Pergamon, Oxford, 1975, Vol. 4). 

Wahlig, E. Dingeldein, R. Bergmann, and K. Reuss, J. Bone Joint Surg., 1978, 60B, 270. 

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Kanke, M., Geissler, R. G., Powell, D., Kaplan, A., and De-Luca, P. P., Interaction of microspheres with blood constituents. III. Macrophage phagocytosis of various types of polymeric drug carriers, J. Parent. Sci. Technol., 42, 157, 1988. 

Probably the most promising polymeric drug carrier system involves polysaccharide molecules. These are natural polymers and are often biodegradable to products that are useful to the host or easily eliminated by the host. Dextrans have been the most extensively used polysaccharide for macromolecular prodrug preparations (79). These materials are biocompatible and the in vivo fate is directly related to their molecular weight. Moreover these macromolecules can be easily targetted to the hepatocytes with D-mannose or L-fucose (20). 

Macromolecules as drug carriers may be divided into degradable and nondegradable types based on their fate within the organism. Biodegradable polymeric drug carriers are traditionally derived from natural products polysaccharides, poly(amino acids) in the hope that the body s natural catabolic mechanisms will act to break down the macromolecular structure into small,... 

Sunamoto J et al. (1987) International Symposium on Polymer Drugs and Polymeric Drug Carriers, 28-30 Oct 1987, Nagasaki ... 

Fig. 3 A tumor-targeted polymer-drug conjugate. The major elements include (i) a polymeric drug-carrier that is water-soluble, bicompatible or biodegradable, non-immunogenic (ii) targeting moieties (iii) a linker between a drug and the carrier. The linker can be a) a chemical bond such as ester or amide. An ester bond is more stable at lysosomal pH than at plasma pH (7.4) while an amide bond is stable at both lysosomal and plasma pH b) an oligopeptide linker that is degradable by specific enzymatic hydrolysis and c) an acid labile linker that is degradable at lysosomal pH but stable at plasma pH.

Unless a carrier conjugate can fulfill the prerequisities listed under (1), (2) and (3), its usefulness is severely limited. Only when a carrier meets requirements (l)- 3) is it necessary to consider the clinical implications of (4) and (5). Fig. 4 illustrates the basic requirements of the polymeric carrier and the characteristic of both a linear and crosslinked polymer. In the following section examples of soluble synthetic polymers specifically synthesized with respect to biomedical applications are given and the importance of their properties relative to polymeric drug carriers is discussed. 

Hg. 4. Essential features of a single-chain and crosslinked polymeric drug carrier... 

A polymeric drug carrier should contain functional groups such as COOH, CHO, NH, and OH which allow the attachment of drugs and targeting moieties. The binding reactions should be simple and, if possible, without side reactions... 

In relation to the polymeric drug carrier, degradability is important with respect to polymer-drug linkages and the long-term fate of polymeric carriers. 

C. Braud, C. Bunel and M. Vert, (1985). Poly( -malic acid) — a new polymeric drug-carrier — evidence for degradation in vitro,... 

K. B. O Hare, R. Dimcan, J. Strohalm, K. Ulbrich and P. Kopeckova, Polymeric drug-carriers containing doxorubicin and melanocyte-stimulating hormone in vitro and in vivo evaluation against murine melanoma, /. Drug Targeting, 1, 217-229 (1993). 

SYNTHESIS, ELECTROCHEMISTRY AND CYTOTOXICITY OF FERROCENE-CONTAINING POLYASPARTAMIDES AS WATER-SOLUBLE POLYMERIC DRUG CARRIER/DRUG CONJUGATES Swarts J C... 

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