F127 pluronic in coformulation with sodium cholate as hosting system for doxorubicin

F127 pluronic in coformulation with sodium cholate as hosting system for doxorubicin Elisamaria Tasca, Mauro Giustini, Luciano Galantini, Karin Schillén* Chemistry Department, University “La Sapienza”, 00185 Rome (Italy), * Division of Physical Chemistry, Department of Chemistry, Lund University, Lund (Sweden) Nonionic pluronic triblock copolymers received considerable attention as modern drug delivery carriers [1]. They have the general formula PEOx-PPOy-PEOx, and are composed of a hydrophobic poly(propylene oxide) (PPO) block and two units of a hydrophilic poly(ethylene oxide) (PEO) block [2]. Their amphiphilic character results into surfactant properties, which includes the ability to interact with hydrophobic surfaces and biological membranes. Above their critical micelle concentration (cmc), these copolymers self-assemble into micelles. Due to their unique core−shell structure, polymeric micelles such as F127 have the ability to solubilize hydrophobic drugs in the PPO core, thereby enhancing their solubility in water media. In addition they are suitable for drug delivery in medicine [3] as they are non-toxic and stabilized to aggregation, protein adsorption and deactivation because of the presence of the PEO corona [4]. The stability of the loaded pluronic micelles is however low due to their high cmc (∼1 mM for F127) resulting in their disaggregation by dilution or interaction with the blood components. The mixture of pluronic micelles with other polymers/surfactants [5,6] enhances the stability of the resulting micelles thus increasing the bioavailability of the encapsulated drugs. To this end, the loading efficiency of bile salt/pluronic coformulation toward the fluorescent anticancer antibiotic doxorubicin (DX) has been studied. DX is administered as chlorohydrate to enhance its solubility in water. This limits its solubilization into F127 micelles to the corona region. To promote its solubility in the hydrophobic core of F127 micelles the coformulation with the cationic bile salt sodium cholate (NaC) has been used. Indeed, in the presence of NaC the DX experience a more apolar environment, as indicated by its fluorescence spectra. The presence of DX seems also to alter the F127 micellar structure, as deduced by DLS experiments. [1] Roesler et al., Adv. Drug Delivery Rev. 2012, 64, 270 [2] S. Ghosh et al., J. Phys. Chem. B 2014, 118, 11437 [3] W. Zhang et al., Biomaterials 2011, 32, 2894 [4] Z. Sezgin et al., Eur. J. Pharm. Biopharm. 2006, 64, 261 [5] P. Singla et al., Spectrochim. Acta A 2018, 191, 143 [6] S. Bayati et al., Langmuir, 2015, 31, 13519