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Low density lipoprotein as a carrier of cytostatics in cancer chemotherapy: Study of stability of drug-carrier complexes in blood
Karolinska Hosp & Inst, Div Clin Pharmacol, Dept Med, S-17176 Stockholm, Sweden Linkoping Univ, Fac Hlth Sci, Dept Clin Pharmacol, S-58185 Linkoping, Sweden Uppsala Univ, Div Toxicol, S-75124 Uppsala, Sweden.
Karolinska Hosp & Inst, Div Clin Pharmacol, Dept Med, S-17176 Stockholm, Sweden Linkoping Univ, Fac Hlth Sci, Dept Clin Pharmacol, S-58185 Linkoping, Sweden Uppsala Univ, Div Toxicol, S-75124 Uppsala, Sweden.
Karolinska Hosp & Inst, Div Clin Pharmacol, Dept Med, S-17176 Stockholm, Sweden Linkoping Univ, Fac Hlth Sci, Dept Clin Pharmacol, S-58185 Linkoping, Sweden Uppsala Univ, Div Toxicol, S-75124 Uppsala, Sweden.
Karolinska Hosp & Inst, Div Clin Pharmacol, Dept Med, S-17176 Stockholm, Sweden Linkoping Univ, Fac Hlth Sci, Dept Clin Pharmacol, S-58185 Linkoping, Sweden Uppsala Univ, Div Toxicol, S-75124 Uppsala, Sweden.
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2000 (English)In: Journal of drug targeting (Print), ISSN 1061-186X, E-ISSN 1029-2330, Vol. 8, no 3, 155-164 p.Article in journal (Refereed) Published
Abstract [en]

Several solid tumour and leukemia cell types have a higher low density lipoprotein (LDL) uptake than the corresponding normal cells. We are investigating the possibilities to use LDL as a drug carrier to increase the selectivity of antineoplastic drugs in cancer chemotherapy. We have developed a method to incorporate lipophilic cytotoxic agents without interfering with the in vitro and in vivo properties of LDL, In this study, we examined the stability of some drug-LDL complexes in blood and plasma as this is an important prerequisite to achieve a selective therapy. The in vitro dialysis of N-trifluoroacetyl-adriamycin-14-valerat-LDL (AD-32-LDL) against plasma revealed a slow dissociation of the complex. The same method showed a fast and total leakage of paclitaxel from paclitaxel-LDL into the plasma chamber. The dissociation of paclitaxel was confirmed by an autoradiographic study of the distribution of paclitaxel-LDL in tumour-bearing mice. In patients with leukemia the rapid plasma dissociation of AD-32 from LDL illustrated a much higher in vivo instability of this complex. With this method, cholesteryl-linoleate only could be incorporated into LDL in a stable manner as shown by dialysis and autoradiography results. The incorporation of cytotoxic drug derivatives, containing lipophilic anchors, is now under study in order to obtain LDL complexes with better plasma stability.

Place, publisher, year, edition, pages
2000. Vol. 8, no 3, 155-164 p.
Keyword [en]
drug carrier, LDL, LDL receptors, antineoplastic drugs, cancer chemotherapy
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Medical and Health Sciences
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URN: urn:nbn:se:liu:diva-49650OAI: oai:DiVA.org:liu-49650DiVA: diva2:270546
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12

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Peterson, Curt

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