title: Fluorescence (fluidity/hydration) and calorimetric studies of interactions of bile acid-drug conjugates with model membranes.
abstract: We have studied the interactions of three bile acid-tamoxifen conjugates, lithocholic acid-tamoxifen (LA-Tam(1)-Am), deoxycholic acid-tamoxifen (DCA-Tam(2)-Am), and cholic acid-tamoxifen (CA-Tam(3)-Am), possessing 1-3 tamoxifen molecules having an amine headgroup with model DPPC membranes and compared with N-desmethylated tamoxifen (TamNHMe) using DPH based fluorescence anisotropy, Prodan based hydration, and differential scanning calorimetry studies. DPH based anisotropy studies showed that bile acid-tamoxifen conjugates increase membrane fluidity, which strongly depends on the number of tamoxifen molecules conjugated to bile acid and the percentage of doping of bile acid-tamoxifen conjugates in the DPPC membranes. The order of membrane fluidity of the coliposomes from bile acid-tamoxifen conjugates and DPPC lipids in gel phase was found to be CA-Tam(3)-Am > DCA-Tam(2)-Am > LA-Tam(1)-Am > TamNHMe. Incorporation of bile acid-tamoxifen conjugates showed an unusual complex behavior of membrane hydration, as evident from Prodan based hydration studies. Temperature dependent study showed incorporation of LA-Tam(1)-Am and DCA-Tam(2)-Am conjugates decreases membrane hydration with an increase in temperature up to the phase transition temperature (T(m)). Differential scanning calorimetry studies showed a decrease in phase transition temperature (T(m)) upon an increase in the percentage of doping of TamNHMe and CA-Tam(3)-Am, whereas LA-Tam(1)-Am and DCA-Tam(2)-Am do not cause a major change in the phase transition temperature (T(m)) of DPPC liposomes. These studies showed the differential behavior of bile acid-tamoxifen conjugates regulating the membrane fluidity, hydration, and phase transition of model membranes depending upon the percentage of doping and tamoxifen conjugation to bile acids.
authors: The Laboratory of Nanotechnology and Chemical Biology, Regional Centre for Biotechnology, 180 Udyog Vihar, Phase 1, Gurgaon 122016, Haryana, India.
authors: Vedagopuram
authors: V
authors: Sreekanth
authors: Avinash
authors: A
authors: Bajaj
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D001647:Bile Acids and Salts / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D019826:Cholic Acid / Q000737:chemistry; D003840:Deoxycholic Acid / Q000737:chemistry; D005454:Fluorescence Polarization; D008081:Liposomes / Q000737:chemistry*; D008095:Lithocholic Acid / Q000737:chemistry; D008958:Models, Molecular; D044367:Phase Transition; D013629:Tamoxifen / Q000737:chemistry*; D044366:Transition Temperature
chemical_list: D001647:Bile Acids and Salts; D008081:Liposomes; D003840:Deoxycholic Acid; D013629:Tamoxifen; D015060:1,2-Dipalmitoylphosphatidylcholine; D008095:Lithocholic Acid; D019826:Cholic Acid