A nanosomal formulation of paclitaxel that reduces toxicity, enhances efficacy and improves quality-of-life

Paclitaxel Formulation Difficulties and Taxol® Toxicities

Paclitaxel is commercially formulated in 50% polyoxyethylated castor oil and 50% dehydrated alcohol (Cremophor EL) to make Taxol®. The Cremophor EL vehicle can have serious side effects, including severe hypersensitivity reactions.

Taxol® has also caused myelosuppression, peripheral neuropathy and other side effects that are dose and schedule related. Consequently, paclitaxel is dose-limited in its current formulation.

Taxosomes® – Improved Efficacy and Reduced Toxicities

To resolve these formulation difficulties and toxicities, we have utilized our CFN technology platform to encapsulate paclitaxel in small, uniform phospholipid liposomes (nanosomes), Taxosomes®. The formulation is Cremophor-free and much less toxic than Taxol®.

Liposomes are microscopic vesicles of phospholipid bilayers comprised of single or multiple lipid bilayers. Most liposomes are non-toxic, non-antigenic and biodegradable in character since they have the molecular characteristics of mammalian cell membranes. Hydrophobic compounds are trapped inside the lipid bilayers, masking the toxic nature of paclitaxel and permitting a biocompatible formulation to be administered.

In vitro studies showed that at the higher dose paclitaxel in either form was very toxic to three breast cancer cell lines. At the lower dose, Taxosomes® was less toxic than Taxol®. In vivo studies showed a markedly greater effect of Taxosomes® on tumor growth in nude mice with breast cancer xenografts than either the control group or the Taxol® group. Tumor volume in the Taxosomes® treated group was approximately 50% that of the Taxol® treated group.

Harvard Medical School researchers have demonstrated that Taxosomes® is much less toxic in vitro than Taxol® while being twice as effective in the in vivo treatment of nude mice with breast cancer xenografts.

Taxosomes® Advantages and Benefits

• Enhanced therapeutic efficacy
• Elimination of pre-medication to counteract the Cremophor
• Reduction of drug toxicity side effects
• Prolonged circulation time and therapeutic effect
• Improved quality-of-life