Systemic Administration of Alkylphosphocholines

Erucylphosphocholine and Liposomal Hexadecylphosphocholine
  • R. Kaufmann-Kolle
  • M. R. Berger
  • C. Unger
  • H. Eibl
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 416)

Abstract

The class of alkylphosphocholinesl[1], best represented by hexadecylphosphocholine (HePC), shares common structural and physical properties with the lysolecithins, yet their biological activities vastly differs[2–6]. An understanding of this behaviour arises from the fact that while alkylphosphocholines, lysolecithins and (ether)-lysolecithins as well incorporate into cell membranes, alkylphosphocholines are metabolically more stable under physiological conditions. We demonstrated that this stability-induced concentration could be used to initiate an antineoplasic response in the cells of methylnitroso urea (MNU) induced mammary carcinomas of Sprague-Dawley (S-D) rats[7,8]. In the same model, lysolecithins and (ether)lysolecithins were inactivated by degradation or acylation. Based on this evidence, clinical investigations on the scope of HePC’s application began in the late nineteen eighties[9]. Success emerged in 1992, with the approval of its use, under the tradename of Miltex®, for the topical treatment of skin tumors which originated from the breast. Although, approved for topical usage, the oral administration of HePC has been limited by the appearance of nausea and vomiting (at dosages below the effective) and thrombophlebitis following i.v. administration, respectively. Liposomes, bilayer spheres of phospholipids, provide an unique tool to deliver toxic species, such as HePC, to their cellular targets. Currently, our efforts focus on gaining an understanding of the effects that modification of HePC has on its ability to be delivered in a liposomal fashion (i.e., HePC-SUVs). Wherein, the crucial factors must support an increased tolerance for oral and intravenous administration. Beyond, we provide a detailed account of the effects of elongating the carbon chain (i.e., from C16 to C22) and introducing a cis-alkene at the ω-9 position. This was accomplished by changing the hexadecyl to the erucyl chain.

Keywords

Visceral Leishmaniasis Mammary Carcinoma Oral Application Median Tumor Volume Methylnitroso Urea 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • R. Kaufmann-Kolle
    • 1
  • M. R. Berger
    • 2
  • C. Unger
    • 3
  • H. Eibl
    • 1
  1. 1.Max-Planck-Institut für biophysikalische Chemie Am FassbergGöttingenGermany
  2. 2.Institut für ToxikologieDKFZHeidelbergGermany
  3. 3.Medizin. UniversitätsklinikGöttingenGermany

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