کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2485336 1114352 2008 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Physicochemical Characterization and Membrane Binding Properties of Camptothecin
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Physicochemical Characterization and Membrane Binding Properties of Camptothecin
چکیده انگلیسی
The intrinsic solubility of the CPT-lactone free base in acidic pH was determined to be 3.44 and 5.11 µM at 22 and 37°C, respectively. The equilibrium solubility of the drug was found to increase with increasing temperature and decreasing pH. The enhanced solubility of the drug at very low pH is attributed to the protonation of the nitrogen atom in the ring B and the increased solvency of the highly concentrated acidic media. The logarithmic value of the intrinsic partition coefficient P of the free base CPT-lactone form was estimated to be 1.65, characteristic of a molecule suitable for absorption. Association constants Kf of the drug for bilayers composed of the zwitterionic (DOPC) and the negatively charged (DOPG) were determined at acidic pH by fluorescence anisotropy to be 35.4 ± 4.5 M−1 and 93.1 ± 11.0 M−1, respectively, indicative of the CPT tendency to preferentially bind to negatively charged membranes. The results indicate that at highly acidic media, CPT is positively charged and exists at its stable lactone form of increased solubility and capacity to bind to negatively charged membranes. These features could be used to invent novel formulation strategies to optimize the antitumor activity of CPT. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4379-4390, 2008
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 97, Issue 10, October 2008, Pages 4379-4390
نویسندگان
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