Block copolymer carrier systems for translymphatic chemotherapy of lymph node metastases.
The presence of lymph node metastases relevantly and significantly impairs disease-specific survival in patients suffering from squamous cell carcinoma of the upper aerodigestive tract. In a VX2 animal tumor model, we present an interstitial translymphatic therapeutic approach using cis-diaminedichloro-platinum(II) (CDDP) conjugated to a poly(ethylene oxide)-block-poly(lysine) (PEO-b-PLys) block copolymer tracking systems for the successful treatment of lymph node metastases. Most effective was the application of a high cargo-load CDDP tracking system (48 wt. % CDDP) curing 90% of the animals and causing only minor local side-effects. Systems containing 1 or 10 wt. % of CDDP were less effective but still cured 50% of the animals. Moreover, the administration of 1 or 10 wt. % of CDDP consistently limited tumor growth to the draining lymph nodes (50%) and prevented systemic distribution of the metastasis even'with 1 wt. % CDDP load. The systems contained 0.25-0.003 mg/kg per body weight CDDP compared to 1 ml/kg per body weight as usually used for intravenous administration. This approach encourages further and more detailed research of a CDDP-based interstitial translymphatic administration of chemotherapy for lymphogenic metastasizing carcinomas in different body regions.
Dünne
Anja A
AA
Department of Otolaryngology, Head and Neck Surgery, Philipps University, 35037 Marburg, Germany.
Boerner
Hans G
HG
Kukula
Hildegard
H
Schlaad
Helmut
H
Wiegand
Susanne
S
Werner
Jochen A
JA
Antonietti
Markus
M
D000818:Animals; D003035:Cobalt / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers; D005260:Female; D015552:Injections, Intralesional; D008207:Lymphatic Metastasis; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry; D011107:Polylysine / Q000008:administration & dosage* / Q000737:chemistry; D011817:Rabbits
D004337:Drug Carriers; C032099:diamminedichlorocobalt(II); D011107:Polylysine; D003035:Cobalt; D011092:Polyethylene Glycols