HPMA copolymer conjugates

Fig. 19. Body distribution of adriamycin-HPMA copolymer conjugates 1 h after intravenous administration to rats. The distribution of a targetable conjugate containing the galactosamine moiety is compared with a conjugate without targeting moiety. Based on data from [264]...

As mentioned in Sect. 2.2.3, the biodistribution of HPMA copolymers depends on many factors. Molecular weight influences the uptake in the isolated tissue of yolk sac [266] as well as the elimination in vivo [124, 125,267,268]. Nonspecific increase in the rate of polymer uptake can be achieved by incorporation of positively charged or hydrophobic comonomers into the HPMA copolymer structure, such as methacryloyloxyethyltrimethylammonium chloride [22], N-methacryloyltyrosinamide [21], or N-[2-(4-hydroxyphenyl)ethyl]acrylamide [267]. The incorporation of hydrophobic moieties may influence the solution properties of the HPMA copolymer conjugates [132,134,269]. The interaction with the cellular surface may depend on the association number and the stability of the micelles. 

Table 7. Combined chemotherapy and photodynamic therapy of A/J mice bearing Neuro 2A neuroblastoma tumors using HPMA copolymer conjugates (from [42])...

Figure 5.5 Chemical structure of a doxorubicin-N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer conjugate...

Figure 1 Schematic representation of the variety of HPMA copolymer conjugate architectures and compositions under study.

Table 2 HPMA Copolymer Conjugates Containing Proteins and Peptides...

Many HPMA copolymer conjugates have been described. They contain drugs (Table 1), proteins, antibodies, and targeting ligands (Table 2). Although many subtle changes... 

Figure 2 Synthesis of HPMA copolymer conjugates via polymer analogous reaction.

Figure 5 Linking chemistries used to bind drugs and targeting residues to HPMA copolymer conjugates.

Figure 8 Release of aminoellipticine (APE) from HPMA copolymer conjugates during incubation with mixtures of isolated lysosomal enzymes (tritosomes). The results shown represent HPMA copolymer-Gly-Phe-Leu-Gly(5mol%)-APE (la,lb) HPMA copoly-mer-Gly-Phe-Leu-Gly(10 mol%)-APE (2a) and HPMA copolymer-Gly-Gly(5 mol%)-APE (3a). The numbers in bold represent the same samples but incubated without tritosomes. (From Ref. 96.)...

Jensen et al. (211) recently suggested that a small fraction of HPMA copolymer conjugate initially entrapped within lysosomes could escape into the cytosol and then traffic to the nucleus. The process was promoted by addition of nuclear... 

Figure 15 Structure of HPMA copolymer conjugates containing doxorubicin, aminoglutethimide and a combination with both drugs pendant to the same chain. Peptidyl linkers -R- comprising Gly-Gly or Gly-Phe-Leu-Gly have been used. (From Ref. 101.)...

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