Enhanced Permeability and Retention EPR of HPMA Copolymer Anticancer Agents

Compounding interest in the efficacy of HPMA copolymer delivery is the fact that regardless of the presence or absence of a selective targeting moiety, HPMA copolymer-drug conjugates accumulate preferentially in solid tumors, through the enhanced permeability and retention (EPR) effect conceptualized by Maeda. 13,14,23 The EPR effect is attributed to 1) high vascular density in the tumor secondary to abnormal vascular architecture and angiogenesis 2) increased permeability of tumor vessels due...

Regulatory Issues With Polymer Therapeutics

Just slightly over a decade ago many individuals in the pharmaceutical sector believed that polymer therapeutics would stand little, if any chance, to be approved by regulatory authorities, particularly, as injectable formulations. Today those views are clearly obsolete. However, many questions regarding the regulatory approval of the polymer therapeutics still exist. Investigators working in the field of polymer therapeutics need to focus on addressing those questions in order to provide the...

References

J., Dvorak, A. M., Perruzzi, C. A., Harvey, V. S., and Dvorak, H. F., 1983, Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219 983-985. 2. Asano, M., Yukita, A., Matsumoto, T., Kondo, S., and Suzuki, H., 1995, Inhibition of tumor growth and metastasis by an immunoneutralizing monoclonal antibody to human vascular endothelial growth factor vascular permeability factor. Cancer Res. 55 52965301. 3. Maeda, H., and...

PEGPAsp Dox Micelles

PEG-PAsp(Dox) micelles are a first generation of polymeric micellar drug developed in our laboratory (Fig. 2) 8, 50. In this formulation, Dox was covalently linked to the side chain of the PAsp segment via an amide bond between the carboxylic group in PAsp and the primary amino group of the glycosidyl residue in Dox. Chemical conjugation of Dox into the PAsp segment with substitution ratio of approximately 50 provided the PAsp segment with sufficient hydrophobicity to form a stable inner core...

Perspectives Of rMETase

A novel approach to the treatment of brain tumors with the combination of rMETase chemotherapeutic regimens that are currently used against such tumors has recently been carried out. The growth of Daoy, SWB77, and D- 54 xenografts implanted subcutaneously in athymic mice was arrested after the depletion of mouse plasma methionine (MET) with a combination of MET- and choline-free diet and rMETase. The treated tumor-bearing mice were rescued from the toxic effects of MET withdrawal with daily...

Info

Blood urea nitrogen (BUN), 167, 212 Bone marrow-cellularity, 36 Bradykinin, 36 C-26 bearing mive, 168 CA 125, 130, 188 CA 15-3, 130, 131 CA 19-9, 130, 131, 188 CA 72-4, 130, 131 Cancer colon, 95 non-small-cell lung, 95 ovarian, 95, 96 Camptothecin analog, 146 Carboxymethyldextran polyalcohol (CM-Dex-PA), 145 Carcinomatosis, 45 Cathepsins, 146 Cationic polymer, 33 CDDP- complexed PEG-PAsp (PEG-Pasp(CDDP)) block copolymers, 165 CDDP- complexed polymeric micelles, 165 Cisplatin...

Synthesis of PEGAsparaginase

E.coli asparaginase, a 140,000 dalton monomer, is composed of four subunits, each with an active site. PEG-asparaginase Oncaspar is prepared by reacting E. coli EC2 asparaginase with succinimidyl succinate-PEG, essentially as described by Abuchowski et al.16. PEG is attached to 64 of the 88 amino groups, or 14 PEG groups per subunit. The conjugate retains 51 of the original activity. A later paper by Ho et al.11 on the clinical pharmacology of PEG-asparaginase contains footnote data that can be...