The main objective of this study was to synthesize novel folic acid-functionalized diblock copolymer micelles and evaluate their solubilizationof two poorly water-soluble anti-tumor drugs, tamoxifen and paclitaxel, which suffer from low water solubility and/or poor hydrolytic stability.The diblock copolymer consisted of a permanently hydrophilic block comprising 2-(methacryloyloxy)ethyl phosphorylcholine (MPC) residuesand a pH-sensitive hydrophobic block comprising 2-(diisopropylamino)ethyl methacrylate (DPA) residues. Folic acid (FA) was conjugated to theend of the MPC block so that this group was located on the micelle periphery. Tamoxifen- and paclitaxel-loaded micelles were prepared from FA–MPC–DPA copolymers prepared with two different block compositions that were designed to produce optimal solubilization of each drug. Theirdrug-loading capacities and aqueous stabilities were determined by high performance liquid chromatography. The hydrodynamic diameters oftamoxifen- and paclitaxel-loaded FA–MPC–DPA micelles ranged from 30 to 60 nm, as judged by dynamic light scattering (DLS) andtransmission electron microscopy (TEM) studies. Finally, tamoxifen and paclitaxel release profiles were evaluated in phosphate buffer solution atpH 7.4 and 5. These studies demonstrated that FA–MPC–DPA micelles acted as useful drug carriers, leading to relatively slow release of bothtamoxifen and paclitaxel into aqueous solution over a period of 7 days. In addition, rapid release can be triggered by lowering the solution pH to 5,which leads to protonation of the DPA block and hence rapid micellar dissociation.
|Numero di pagine||10|
|Stato di pubblicazione||Published - 2006|
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