HYDROXYPROPYL METHACRYLAMIDE

Yang JY, Xu CY, Wang C et al (2006) Refolding hydrogels self-assembled from n- (2-hydroxypropyl)methacrylamide graft copolymers by antiparallel coiled- coil formation. Biomacromolecules 7 1187-1195... 

One of the most successful conjugate polymer systems was developed by Duncan and Kopecek (25). The polymer carrier used in their system is poly [N(2-hydroxypropyl) methacrylamide] a biocompatible polymer that was originally developed as a plasma extender. They have evaluated a number of polymer conjugated drugs for cancer chemotherapy with interesting results. The attachment of the drug is through a peptidyl spacer pendent to the polymer backbone. These peptides links are stable in aqueous media but are readily hydrolyzed intracellularly... 

Semitelechelic Poly[A -(2-hydroxypropyl)-methacrylamide] for Biomedical Applications... 

Methoxy poly(ethyleneglycol) (mPEG) was the most frequently used semitelechelic polymer for over 2 decades. It has been successfully used for the modification of various proteins, biomedical surfaces and hydrophobic anticancer drugs (for reviews see References [3,9,10]. Recently, a number of new semitelechelic (ST) polymers, such as ST-poly(A -isopropylacry-lamide) (ST-PNIPAAM) [11-15], ST-poly(4-acryloylmorpholine) (ST-PAcM) [16], ST-poly(A-vinylpyrrolidone) (ST-PVP) [17], and ST-poly[A-(2-hydroxypropyl)methacrylamide] (ST-PHPMA) [18-21] have been prepared and shown to be effective in the modification of proteins or biomedical surfaces. 

Figure 4 Chemical structure of AA-(2-hydroxypropyl)methacrylamide (HPMA) and A-(A, A -dicarboxymethylaminopropyl)methacrylamide (DAMA).

For cancer therapy, the well estabhshed N(-2-hydroxypropyl)methacrylamide (HMPA) polymers have been extensively studied. PKl, a 28-kDa HPMA copolymer containing doxorubicin (Figure 1.3) is now in clinical testing [15]. Other drugs that have been incorporated... 

A phase I clinical and pharmacokinetic study of PKl comprising doxorubicin covalently bound to N-(2-hydroxypropyl)-methacrylamide copolymer by a peptidyl linker, was carried out in 36 patients with refractory or resistant cancers [94], PKl demonstrated anti-tumour activity, and that polymer-drug conjugation decreased doxorubicin dose-limiting toxicities. Phase II studies are in progress. 

Steric stabilization of poly-l-lysine/DNA complexes by the covalent attachment of semitelechelic poly [A-(2-hydroxypropyl)methacrylamide]. Bioconjugate Chem., 11, 492-501. 

Ambler, L. E., L. Brookman, J. Brown, P. Goddard, and K. Petrak. 1992. Soluble polymeric carriers for drug delivery. 5. Solution properties and biodistribution behavior of n-(2-hydroxypropyl)methacrylamide-co-r>(2-[4-hydroxy phenyl]ethyl)-acrylamidecopolymers substituted with cholesterol Bioact. 

Seymour, L. W., R. Duncan, J. Strohalm, and I. Kopecek. 1987. Effect of molecular weight (Mw) of N-(2-hydroxypropyl)methacrylamide copolymers on body distribution and rate of excretion after subcutaneous, intraperitoneal, and intravenous administration toJraSSomed. Mater. Res. 21 1341-1358. 

Duncan, R., L C. Seymour, L. Scarlett, J. B. Lloyd, P. Rejmanova, and J. Kopecek. 1986. Fate of N-(2-hydroxypropyl)methacrylamide copolymers with pendent galactosamine residues after intravenous administration to ratfiiochim. Biophys. Act880 62-71. 

Duncan, R., P. Kopeckova-Rejmanova, J. Strohalm, I. Hume, H. C. Cable, J. Pohl, J. B. Lloyd, and J. Kopecek. 1987. Anticancer agents coupled1e(2-hydroxypropyl)methacrylamide copolymers. I. Evaluation of daunomycin and puromycin conjugates/itro. Br. J. Cancei55 165-174. 

Oupicky, D., Konak, C. and Ulbrich, K. (1999b) DNA complexes with block and graft copolymers of N-(2-hydroxypropyl)methacrylamide and 2-(trimethylammonio)ethyl methacrylate. J. Biomater. Sci. Polym. Ed., 10, 573-590. 

Wolfert et al. (1996) examined the transfection and cytotoxicity of poly (V-2-hydroxypropyl methacrylamide)-/>-poly(trimethylaminoethyl methacrylate) (PHPMA-PTMAEM), an amino methacrylate... 

David, A., et al. 2002. The role of galactose, lactose, and galactose valency in the biorecognition of lV-(2-hydroxypropyl)methacrylamide copolymers by human adenocarcinoma cells. Pharm Res 19 1114. 

To avoid inactivation of the biological molecules in vivo by interaction with blood (or tissue) fluids and by clearance mechanisms, it may be desirable to coat the delivery system with a hydrophilic polymer such as polyethylene glycol and poly-[W-(2-hydroxypropyl)methacrylamide]. 

Vasey, P. A., Kaye, S. B., Morrison, R., et al. Phase I clinical and pharmacokinetic study of PK1 [lV-(2-hydroxypropyl)methacrylamide copolymer doxorubicin] First member of a new class of chemotherapeutic agents-drug-polymer conjugates. Cancer Research Campaign Phase I/II Committee. Clin. Cancer Res. 5(l) 83-94. 1999. 

Sprincl, L., Exner, J., Sterba 0., and Kopecek, J. New types of synthetic infusion solutions III. Elimination and retention of poly-[Af-(2-hydroxypropyl)methacrylamide] in a test organism. J. Biomed. Mater. Res. 10(6) 953-963. 1976. 

Rihova, B., Kopecek, J., Ulbrich, K, et al. Effect of the chemical structure of N-(2-hydroxypropyl)methacrylamide copolymers on their ability to induce antibody formation in inbred strains of mice. Biomaterials 5 143-148, 1984. 

Rihova, B., Bilej, M., Vetvicka, V., et al. Biocompatibility of IV-(2-hydroxypropyl) methacrylamide copolymers containing adriamycin Immunogenicity, and effect on haematopoietic stem cells in bone marrow in vivo and mouse splenocytes and human peripheral blood lymphocytes in vitro. Biomaterials 10 335-342, 1989. 

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