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'binds to albumin; b SBTI, Kunitz type;c DTPA, diethylenetriaminepentaacetic acid; d PEG, polyethylene glycol;e Human albumin in humans: 19 days;f Human.

'binds to albumin; b SBTI, Kunitz type;c DTPA, diethylenetriaminepentaacetic acid; d PEG, polyethylene glycol;e Human albumin in humans: 19 days;f Human.

Another notion to be emphasized is that polymeric drugs should not be cationic but either neutral or anionic because the luminal surface of blood vessels is highly negatively charged, and thus cationic polymer drugs are adsorbed on the vascular surface and are expected to have a short in vivo half-life. In addition, it is obvious that these molecules should not exhibit antigenic or immunogenic characteristics3-6.

Figure 2. A. Intratumor accumulation of various 51Cr-tagged proteins in solid tumor-bearing mice: o, neocarzinostatin (NCS) (12 kDa); •, SMANCS (16 kDa, but known to bind to albumin); ovomucoid (29 kDa); □, bovine serum albumin (69kOa); mouse serum albumin (68 kDa); □, mouse immunoglobulin G (160 kDa). Radiolabeled proteins were injected i.v. at time zero. Values are based on radioactivity (cf. Fig. 2). The tumor model in both A and B was solid sarcoma S-180 in mice. (From ref. 26, with permission). B. Relationship of drug distribution and molecular size to plasma concentration, AUC (area under the concentration curve), renal clearance, and intratumor uptake as expressed by percentage of injected dose. Putative polymer drugs are l25I-Tyr-HPMA-copolymers of

Figure 2. A. Intratumor accumulation of various 51Cr-tagged proteins in solid tumor-bearing mice: o, neocarzinostatin (NCS) (12 kDa); •, SMANCS (16 kDa, but known to bind to albumin); ovomucoid (29 kDa); □, bovine serum albumin (69kOa); mouse serum albumin (68 kDa); □, mouse immunoglobulin G (160 kDa). Radiolabeled proteins were injected i.v. at time zero. Values are based on radioactivity (cf. Fig. 2). The tumor model in both A and B was solid sarcoma S-180 in mice. (From ref. 26, with permission). B. Relationship of drug distribution and molecular size to plasma concentration, AUC (area under the concentration curve), renal clearance, and intratumor uptake as expressed by percentage of injected dose. Putative polymer drugs are l25I-Tyr-HPMA-copolymers of various molecular sizes given i.v. at 1.8 xlO mice. (From ref. 28 with permission).

cpm. The tumor model was sarcoma S-180 in

Table 3 Pharmacokinetic parameters of native and polymer conjugated interferon in human. monkey, rat and mice.

Types on

Approximate

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