title: Evaluation of lipid-coated microbubbles as a delivery vehicle for Taxol in brain tumor therapy.
abstract: OBJECTIVE
  This work evaluates the potential of lipid-coated microbubbles (LCM) as a delivery vehicle for lipid-soluble antineoplastic agents. We have shown, in rats, the selective affinity of intravenously administered LCM for tumor cells. They are internalized by the tumor cells both in vitro and in vivo. The specificity of LCM for tumors and subsequent incorporation into the cytoplasm could significantly reduce the systemic effects of an agent incorporated into the bubbles, such as Taxol.
  
  
  METHODS
  The in vitro methods were as follows. C6 cells (10(5) cells) were treated with Taxol-LCM (6 micrograms/ml), Taxol-Cremophore (6 micrograms/ml), or LCM alone for 8 or 24 hours. Cell death was determined by staining the cells with nuclear staining. Abnormalities of microtubule structures were ascertained by confocal microscopy. The in vivo methods were as follows. Two rat tumor models (C6 and 9L) were used. Rats were treated with single bolus injections or with repetitive (two or three) treatment courses, with respective control animals. Each course consisted of one daily tail vein injection for 5 consecutive days and then 2 days of rest.
  
  
  RESULTS
  When compared with either a saline control group or a group receiving Taxol in an oil vehicle, Taxol-LCM reduced tumor progression in Fischer 344 rats inoculated with 9L glioma. The most profound effect was observed with rats treated with three treatment cycles (five daily injections/cycle) separated by two rest periods (2 d/period).
  
  
  CONCLUSIONS
  Both in vitro and in vivo data indicate that Taxol can be incorporated into LCM, can be delivered to the tumor site, and can exert a measurable antitumor biological effect.
authors.affiliation: Division of Neurosurgery, University of Connecticut Health Center, Farmington, Connecticut, USA.
authors.forename: S Y
authors.initials: SY
authors.lastname: Ho
authors.forename: E
authors.initials: E
authors.lastname: Barbarese
authors.forename: J S
authors.initials: JS
authors.lastname: D'Arrigo
authors.forename: C
authors.initials: C
authors.lastname: Smith-Slatas
authors.forename: R H
authors.initials: RH
authors.lastname: Simon
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000473:pathology*; D002214:Capsules; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers; D005910:Glioma / Q000473:pathology; D018316:Gliosarcoma / Q000473:pathology*; D006801:Humans; D008081:Liposomes; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002214:Capsules; D004337:Drug Carriers; D008081:Liposomes; D017239:Paclitaxel