The successful treatment of malignant brain tumours has been thwarted by the inability to define the boundary of the infiltrating tumours and also by the presence of transformed tumour cells in the region which are undetectable. Malignant glioma almost always recurs locally, suggesting that more effective identification and control of the tumour boundary might be of some value. This has motivated a search for vehicles that have a specific affinity for tumour cells.
Taxol functions as an antineoplastic agent. Preclinical tumour screens have proven that Taxol affects a variety of tumour models (1). Because of Taxol's lipophilicity, it is difficult to administer and to deliver to the target tissues. Different vehicles have been tested to dissolve Taxol because of it's toxicity to many normal tissues (1).
The traditional oil-based vehicle used to deliver Taxol, consists of polyoxyethylated caster oil (CRE) and 50% absolute alcohol. This vehicle is also toxic and CRE is known to cause undesirable side effects in animals and humans (2).
Recently, reformulation of Taxol in liposome has demonstrated growth-inhibiting activity against a variety of tumour cell lines (3), including Colon-26, a Taxol-resistant murine tumour. The disadvantage of liposomes are their poor targeting ability and their rapid clearance from the circulatory system. Attachment of polyethylene glycol to liposomes has prolonged liposome clearance time at the expense of targeting specificity.
A recent development is the use of lipid-coated microbubbles (LCM)
as a delivery vehicle for lipid soluble antineoplastic agents such as
Taxol. This is due to LCM's tumour targeting ability and it's ability
to stay at the tumour site and/ or within the tumour cell for several
minutes.
LCM are microbubbles with lipid monolayer skins consisting of
cholesterol esters and triglycerides.Taxol can be incorporated into
LCM's due to their thermodynamic properties and more importantly due
to the lipid solubility of Taxol.
LCM differ from liposomes in many respects, most notably they are a lipid monolayer with no hydrophilic component. Because they are uncharged, they are unlikely to be captured during circulation. The charge neutrality greatly increases the blood-tissue compatibility. The monolayer encloses only a gaseous interior and as a consequence, LCM's are physically flexible. Another important property, is the ability of LCM to lodge in the tumour target site, where they remain, without recirculation until they become degraded in the tumour cell cytoplasm.
LCM-Taxol is administrated intravenously and is carried to the tumour site where the target specificity of these bubbles reduces the systemic effect of Taxol.
LCM-Taxol exerts a anti tumour effect against brain tumour cells both in vitro & in vivo.
REFERENCES
Main Source:-
Shih-Yieh Ho, E.Barbarese, J.S.D'Arrigo: Neurosurgery Vol 40, No. 6,
June 1997
(1) National Cancer Institute, Clinical brochure Taxol, Sep.
1983
(2) R.B.Weiss, T.C.Donehower: J. Clinical Oncology 8, 1263-1268,
1990
(3) A.Sharma, E.Mayhew, R.M.Straubinger: Cancer Res. 53: 5877-5881,
1993
