Abstract
Poly(β-malic acid), PMLA, is known as a worthwhile degradable and bioresorbable drug carrier, which bears pendent reactive carboxylic acid groups usuable to tailor make macromolecular prodrugs. Fluoresceinamine (Fl), has been covalently bound to poly(malic acid) as a model of a drug molecule to prospect the fate of poly(malic acid)-drug conjugate in contact with living cells, and especially cell uptake. For this, Fl was bound to poly(β-malic acid) through amide bound using DCC as the coupling agent. Three partially benzylated Fl-PMLA conjugates were also synthesized by attachement of benzyl alcohol residues to pendent carboxylic acid groups via ester bonds. LASER-microspectrofluorometry (L-MSF) and fluorescence microscopy were used to evaluate the in vitro uptake of the conjugates by tumor cells K562 (A human erythroleukemia). It is shown that cell uptakes are polymer-dependent, molecular weight-dependent and hydrophobe-dependent.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Zunino F, Savi G, Giuliani F, Gambetta R, Supino R, Tinelli S and Pezzoni G. (1981) Comparison of antitumor effects of daunorubicin covalently linked to poly-L-amino acid carriers. Eur J Cancer Clin Oncol 20: 121–125
Daussin F, Boschetti E, Delmotte F and Monsigny M. (1988) p-Benzylthiocarbamoyl-aspartyl-daunorubicin-substituted polytrisacryl: a new drug acid-labile arm-carrier conjugate. Eur J Biochem 176: 625–628
Yokoyama M, Miyauchi M, Yamada N, Okano T, Sakurai Y, Kataoka K and Inoue S. (1990) Polymer micelles as novel drug carrier: adriamycin-conjugated poly(ethylene glycol)-poly(aspartic acid) block copolymer. J Control Rel 11: 269–278
Shih LB, Goldenberg DM, Xuan H, Lu H, Sharkey RM and Hall TC. (1991) Anthracycline immunoconjugates prepared by a site-specific linkage via an amino-dextran intermediate carrier. Cancer Res 51: 4192–4198
Vert M. (1986) Polyvalent polymeric drug carriers. CRC Crit Rev The. Drug Carrier Syst 2: 291–327
Seymour LW, Duncan R, Kopecek P and Kopecek J. (1987) Daunomycin-and adriamycin-N-(2-hydroxypropyl)methacrylamide copolymer conjugates; toxicity reduction by improved drug-delivery Cancer Treatment Rev 14: 319–327
Dumitriu S, Popa M and Dumitriu M. (1989) Polymeric biomaterials as enzyme and drug carriers. Part IV: polymeric drug carriers systems. J Bioact Compat Polym 4: 151–197
Ohya Y, Hirai K and Ouchi T. (1992) Synthesis and cytotoxic activity of doxorubicin bound to poly(α-malic acid) via ester or amode bonds. Makromol Chem 193: 1881–1887
Braud C and Vert M. (1993) Poly(β-malic acid) based biodegradable polyesters aimed at pharmacological uses. Trends in Polymer Science 3: 57–65
Gigli M, Doglia SM, Millot JM, Valentini L and Manfait M. (1988) Quantitative study of doxorubicin in living cells nuclei by microspectrofluorometry. Biochem Biophys Acta 950: 13–20
Gigli M, Rosoanaivo TWD, Millot JM, Jeannesson P, Rizzo V, Jardillier JC, Arcamone F and Manfait M. (1989) Correlation between growth inhibition and intranuclear doxorubicin and 4′-deoxy-4′iododoxorubicin quantitated in living K562 cells by microspectrofluorometry. Cancer Res 49: 560–566
Delplace F, Flan B, Montreuil J, Lenain B, Barbillat J and Delhaye M. (1990) Analysis of fluorescent products and study of their interaction with cells by means of laser-microspectrofluorometry. Analusis 18: 27
Vert M and Lenz RW. (1981) Malic acid polymers. US Patent 4: 265, 247
Lozzio CB and Lozzio BB. (1975) Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome. Blood 45: 321–334
Ginot L, Jeannesson P, Angiboust JF, Jardillier JC and Manfait M. (1984) Interactions of adriamycin in sensitive and resistant leukemic cells: a comparative study by microspectrofluorometry. Studia Biophys 9: 45–48
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1996 Springer-Verlag Tokyo
About this paper
Cite this paper
Abdellaoui, K., Boustta, M., Morjani, H., Manfait, M., Vert, M. (1996). Penetration of Polymeric Drug Carriers into K562 Cells. In: Ogata, N., Kim, S.W., Feijen, J., Okano, T. (eds) Advanced Biomaterials in Biomedical Engineering and Drug Delivery Systems. Springer, Tokyo. https://doi.org/10.1007/978-4-431-65883-2_11
Download citation
DOI: https://doi.org/10.1007/978-4-431-65883-2_11
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-65885-6
Online ISBN: 978-4-431-65883-2
eBook Packages: Springer Book Archive