Drug delivery to the brain using thermosensitive liposome and local hyperthermia.
We investigated the possibilities of drug delivery to the brain using thermosensitive liposomes and hyperthermia. Thermosensitive liposomes are small vesicles containing some drugs, which are designed to release the drugs in response to hyperthermia. The first experiment consisted of four groups: (1) received free Cisplatin: cis-diamminedichloroplatinum (CDDP); (2) received free CDDP and above 41 degrees C local brain heating for 30 min; (3) received liposomes containing CDDP (CDDP-liposome); and (4) received CDDP-liposome and above 41 degrees C local brain heating for 30 min. Brain CDDP levels were significantly higher in (4), while those on the other groups were undetectable. In the second experiment, we studied the distribution of Evans blue (Eb) in the artificially heated region of mongrel dogs' brain. One group received free Eb and the other group received liposomes containing Eb (Eb-liposome). While the extravasation of free Eb was localized in regions heated > 44 degrees C, that of Eb-liposome was extended up to the regions heated at 41 degrees C. We concluded that the use of thermosensitive liposomes and hyperthermia not only contributes to the brain tumour killing as direct thermal killing does but also helps to increase the concentration of chemotherapeutic drugs into the tumour invaded zones with mild local hyperthermia of 41 degrees C.
Kakinuma
K
K
Department of Neurosurgery, Niigata University, Japan.
Tanaka
R
R
Takahashi
H
H
Sekihara
Y
Y
Watanabe
M
M
Kuroki
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics; D003131:Combined Modality Therapy; D004285:Dogs; D016503:Drug Delivery Systems / Q000379:methods*; D006979:Hyperthermia, Induced / Q000379:methods*; D008081:Liposomes; D051381:Rats; D011916:Rats, Inbred F344; D013696:Temperature
D000970:Antineoplastic Agents; D008081:Liposomes; D002945:Cisplatin