Sterol-Modified Phospholipids: Cholesterol and Phospholipid Chimeras with Improved Biomembrane Properties Export

@article{citeulike:3450992, abstract = {Abstract: We synthesized a family of sterol-modified glycerophospholipids (SML) in which the sn-1 or sn-2 position is covalently attached to cholesterol and the alternative position contains an aliphatic chain. The SML were used to explore how anchoring cholesterol to a phospholipid affects cholesterol behavior in a bilayer. Notably, cholesterol in the SML retains the membrane condensing properties of free cholesterol regardless of the chemistry or position of its attachment to the glycerol moiety of the phospholipid. SMLs by themselves formed liposomes upon hydration and in mixtures between an SML and diacylglycerophospholipids (C14 to C18 chain length) the thermotropic phase transition is eliminated at the SML equivalent of about 30 mol \% free cholesterol. Osmotic-induced contents leakage from SML (C14C18) liposomes depends upon the linkage and position of cholesterol but in general is similar to that observed in 3/2 diacylphosphatidylcholine/cholesterol (mole ratio) liposomes. SML liposomes are exceptionally resistant to contents release in the presence of serum at 37 °C. This is probably due to the fact that SML exchange between bilayers is more than 100 fold less than the exchange rate of free cholesterol in the same conditions. Importantly, SML liposomes containing doxorubicin are as effective in treating the murine C26 colon carcinoma as Doxil, a commercial liposome doxorubicin formulation. SMLs stabilize bilayers but do not exchange and hence provide a new tool for biophysical studies on membranes. They may improve liposomal drug delivery in organs predisposed to the extraction of free cholesterol from bilayers, such as the skin, lung, or blood.}, address = {Departments of Pharmaceutical Chemistry and Biopharmaceutical Sciences, School of Pharmacy, University of California at San Francisco, San Francisco, California 94143-0912}, author = {Huang, Zhaohua and Szoka, Francis C.}, citeulike-article-id = {3450992}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/ja8065557}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/ja8065557}, day = {25}, doi = {10.1021/ja8065557}, journal = {J. Am. Chem. Soc.}, keywords = {effects, huang08pdf, membrane, phospholipid, sterol}, month = {October}, posted-at = {2008-10-26 01:21:58}, priority = {2}, title = {Sterol-Modified Phospholipids: Cholesterol and Phospholipid Chimeras with Improved Biomembrane Properties}, url = {http://dx.doi.org/10.1021/ja8065557}, year = {2008} }

TY - JOUR ID - citeulike:3450992 L3 - citeulike-article-id:3450992 N2 - Abstract: We synthesized a family of sterol-modified glycerophospholipids (SML) in which the sn-1 or sn-2 position is covalently attached to cholesterol and the alternative position contains an aliphatic chain. The SML were used to explore how anchoring cholesterol to a phospholipid affects cholesterol behavior in a bilayer. Notably, cholesterol in the SML retains the membrane condensing properties of free cholesterol regardless of the chemistry or position of its attachment to the glycerol moiety of the phospholipid. SMLs by themselves formed liposomes upon hydration and in mixtures between an SML and diacylglycerophospholipids (C14 to C18 chain length) the thermotropic phase transition is eliminated at the SML equivalent of about 30 mol % free cholesterol. Osmotic-induced contents leakage from SML (C14C18) liposomes depends upon the linkage and position of cholesterol but in general is similar to that observed in 3/2 diacylphosphatidylcholine/cholesterol (mole ratio) liposomes. SML liposomes are exceptionally resistant to contents release in the presence of serum at 37 °C. This is probably due to the fact that SML exchange between bilayers is more than 100 fold less than the exchange rate of free cholesterol in the same conditions. Importantly, SML liposomes containing doxorubicin are as effective in treating the murine C26 colon carcinoma as Doxil, a commercial liposome doxorubicin formulation. SMLs stabilize bilayers but do not exchange and hence provide a new tool for biophysical studies on membranes. They may improve liposomal drug delivery in organs predisposed to the extraction of free cholesterol from bilayers, such as the skin, lung, or blood. JF - J. Am. Chem. Soc. AD - Departments of Pharmaceutical Chemistry and Biopharmaceutical Sciences, School of Pharmacy, University of California at San Francisco, San Francisco, California 94143-0912 TI - Sterol-Modified Phospholipids: Cholesterol and Phospholipid Chimeras with Improved Biomembrane Properties KW - effects KW - huang08pdf KW - membrane KW - phospholipid KW - sterol AU - Huang, Zhaohua AU - Szoka, Francis PY - 2008/10/25/ UR - http://dx.doi.org/10.1021/ja8065557 ER -