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Paclitaxel Antibody Conjugates and Trehalose for Preserving the Immunulogical Activity After Freeze-Drying

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Abstract:

Antibodies and anticancer drug-antibody conjugates used in experimental cancer research or clinically must be freeze-dried for preserving the activity and storage at room temperature. This often results in some denaturation and loss of activity . We describe a recovery of the cytotoxic activity of a paclitaxel-mAb immunoconjugate after freeze-drying. The paclitaxel-antibody conjugate specific for ovarian cancer was tested both for its cytotoxicity in vitro and immunological activity after freeze drying in the presence of various preservatives.

Results show that the inclusion of trehalose as a stabilizer at concentrations varying from the 0.25 and 0.40M protected the antibody and saved the pharmacological activity. When PEG alone or with trehalose was used, the immunological and cytotoxic activities recovery were lower. Albumin was not protective. This study shows that the addition of trehalose for freeze drying labile drug is a promising method for storage of large quantities of the immunoconjugates for experimental and therapeutic use.

Keywords: cytotoxicity; drug targeting; freeze drying; lyophilization; monoclonal antibody; paclitaxel immunoconjugates; trehalose

Document Type: Review Article

DOI: http://dx.doi.org/10.2174/0929867043455954

Affiliations: Bioxel Pharma Inc, 3075 Des Quatre-Bourgeois (440), Ste Foy, Quebec, Canada G1W 4Y5.

Publication date: February 1, 2004

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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