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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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

Author(s): Jairo Jaime and Michel Page

Volume 11 , Issue 4 , 2004

Page: [439 - 446] Pages: 8

DOI: 10.2174/0929867043455954

Price: $65

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


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