ASSOCIATION AND RELEASE OF PROSTAGLANDIN E-1 FROM LIPOSOMES

PGE1-lipid interactions were studied in several liposome systems. Data from both circular dichroic (CD) measurements and differential scanni ng calorimetry (DSC) indicated that PGE1 in the protonated form seeks the less polar environment of the lipid bilayer. CD measurements made on PGE1 in solution showed that the wavelength of maximum absorbance r ed shifted approximately 8 nm with decreasing solvent polarity. The CD spectrum of liposomal PGE1 prepared in pH 4.5 but not pH 7.2 buffer w as also red shifted. There was no red shift in the CD spectrum of PGE1 detected at pH 4.5 in the absence of phospholipid. DSC measurements o n DSPC bilayers prepared with 5 mol% PGE1 at pH 4.5 but not pH 7.2 rev ealed an almost complete loss of the pre-transition as well as broaden ing of the main phase transition. The amount of H-3-PGE1 initially ass ociated with EPC, POPC or DSPC liposomes was determined using size exc lusion filters and centrifugation. This amount was found to be depende nt on the pH of the buffer (pH 4.5 >> pH 7.2) and fluidity of the bila yer (EPC = POPC > DSPC), but independent of the lamellarity of the lip osome. In all cases, addition of cholesterol reduced the amount of PGE 1 associated with the liposome. The time-dependent release of PGE1 fro m the liposomes was determined by rapidly diluting the sample 100-fold into pH 7.2 buffer. Lipid saturation was a key factor influencing thi s release. Gel-phase liposomes of DSPC showed a rapid initial release (t(1/2) < 2 min) of PGE1, corresponding to the amount in the outer mon olayer, followed by a very slow, almost negligible release of the rema ining PGE1. A rapid initial release also occurred in fluid-phase membr anes, followed by a more gradual release of the remaining PGE1 over se veral hours. This release rate could be slowed by increasing the lamel larity of these liposomes, or adding cholesterol to decrease the fluid ity of the membrane. (C) 1997 Elsevier Science B.V.