Peculiar Mechanism of Solubilization of a Sparingly Water Soluble Drug into Polymeric Micelles. Kinetic and Equilibrium Studies

Complementary kinetic and equilibrium studies on the solubilization process of the sparingly water soluble tamoxifen (TAM) drug in polymeric aqueous solutions have been performed by using the spectrophotometric method. In particular, the amphiphilic copolymers obtained by derivatization of polymeric chain of poly(N-2-hydroxyethyl)-DLaspartamide, PHEA, with poly(ethylene glycol)s, PEG (2000 or 5000 Da), and/or hexadecylamine chain, C16, namely PHEA-PEG2000-C16, PHEA-PEG5000-C16, PHEA-C16, have been employed. Preliminary to the kinetic and equilibrium data quantitative treatment, the molar absorption coefficient of TAM in polymeric micelle aqueous solution has been determined. By these studies the solubization sites of TAM into the polymeric micelles have been determined and the solubilization mechanism has been elucidated through a nonconventional approach by considering the TAM partitioned between three pseudophases, i.e., the aqueous pseudophase, the hydrophilic corona, and the hydrophobic core. The simultaneous solution of the rate laws associated with each step of the proposed mechanism allowed the calculation of the rate constants associated with the involved processes, the values of which are independent of both the copolymer concentration and nature, with the exception of the rate of the TAM transfer from the corona to the core. This has been attributed to the steric barrier, represented by the corona, which hampers the solubilization into the core. The binding constant values of the TAM to the hydrophilic corona of the polymeric micelles, calculated through the quantitative analysis of the equilibrium data, depend on the thickness of the hydrophilic headgroup, while those of the hydrophobic core are almost independent of the copolymer type. Further confirmation to the proposed solubilization mechanism has been provided by performing the kinetic and equilibrium measurements in the presence of PHEA-PEG2000 and PHEAPEG5000 copolymers

Spectrophotometric evidence for the solubilization site of betalain pigments in membrane biomimetic systems

The solubilization site of two betalain pigments, namely, betanin and indicaxantin, into L-\u3b1-dipalmitoylphosphatidylcholine (DPPC) and dimyristoylphosphatidylcholine (DMPC) vesicles was investigated by a spectrophotometric study. Pigment absorbance was monitored by varying phospholipid concentration, at a constant temperature that was varied in a range including the main phase transition temperature (Tm) of the relevant phospholipid bilayer. Maximum betanin absorption increased with the increase of DPPC concentration within the entire temperature range, reaching a plateau. The binding constant (Kb) of the pigment, calculated according to a pseudo-two-phase model, varied with the temperature, indicating that betanin is located at the hydrophobic interior of the bilayer. Other measurements of binding of betanin to DMPC and of indicaxanthin to either DPPC or DMPC vesicles ruled out that these compounds were solubilized in the hydrophobic interior of these bilayers