The antitumor effect of liposome-encapsulated cisplatin on rat osteosarcoma and its enhancement by caffeine.
BACKGROUND
Drug delivery systems are for the purpose of targeting a drug to a specific tissue selectively and at the same time preventing a drug from accumulating in healthy organs. Liposomes have been proposed as useful drug carriers in targeted drug delivery system and are under investigation in several therapeutic fields. Caffeine has been identified as belonging to the group of xanthines that enhances the action of cisplatin.


METHODS
In this study, liposomes containing polyethylene glycol encapsulated cisplatin (CDDP-L) were prepared. The action of CDDP-L on rat osteosarcoma and the enhancing action of caffeine on the antitumor effect of CDDP-L were evaluated. Using osteosarcoma-bearing rats, the retention of CDDP-L in the blood, its intratumor concentration, cytoreductive effect and the enhancing action of caffeine on its antitumor effect were examined.


RESULTS
The liposomes were able to remain in the systemic circulation for a long time and to be concentrated in the osteosarcoma, but that action did not produce an effect corresponding to the quantity of cisplatin which was encapsulated reaching the tumor. In rats administered CDDP-L, it was discovered that the antitumor effect was not only enhanced by the coadministration of caffeine but also further enhanced when the dosing period of caffeine was increased.


CONCLUSIONS
CDDP-L combined with caffeine treatment can produce better results for osteosarcoma.
Karita
Michiaki
M
Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
Tsuchiya
Hiroyuki
H
Kawahara
Masami
M
Kasaoka
Satoshi
S
Tomita
Katsuro
K
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D008081:Liposomes / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D012516:Osteosarcoma / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D008081:Liposomes; D002110:Caffeine; D002945:Cisplatin