Polymer nanomaterials have received a great deal of interest as vehicles used for diagnostic and therapeutic agents. One promising example of these is represented by a class of Pluronic block copolymers. These block copolymers consist of hydrophilic poly(ethylene oxide) (PEO) and hydrophobic poly(propylene oxide) (PPO) blocks arranged in A-B-A tri-block structure: PEO-PPO-PEO. Due to their amphiphilic character, in aqueous solutions at concentrations above critical micelle concentration (cmc) and temperature (cmt) these copolymers self-assemble into core-shell micelles. The core of the micelles consists of hydrophobic PPO blocks that are separated from the aqueous exterior by the shell hydrated of hydrophilic PEO chains. The idea is to realize a drug delivery system by incorporating the drug within the nanocarrier in order to increase solubility, metabolic stability and to improve circulation time of the drug. We have characterized the system with doxorubicin and the idea now is to expand the mixed micellar system to another anthracycline: epirubicin. It is less cardiotoxic than the other anthracycline antibiotics such as doxorubicin and for this reason its use is much more widespread in anticancer therapy. Structural differences among the two molecules are very limited, but sufficient to induce important differences at the clinical level. EPI is the 4¿ epimer of DX. The resulting system will be characterized by the joint use of scattering and spectroscopic techniques. The hydrophilic nature of the particles and the presence of the PEG in the shell could provide a certain level of biocompatibility and stealth characteristics to the mixed system, thus being attractive from an applicational point of view.
Promising candidates as nanocarrier delivery agents for poorly
water soluble drugs, appear to be tri-block copolymers of polyoxyethylene or poly(ethylene oxide) (PEO) and polyoxypropylene or poly(propylene oxide) (PPO) [1] because of the intrinsic stealth nature of the micelles formed [2]. Indeed SP1049C, i.e. a formulation where the copolymers EO100-PO65-EO100, (F127) and EOn/2-POm-EOn/2 (L61; n = 4.55, m = 3.01) spontaneously form micelles that conceal doxorubicin, has entered the phase II/III clinical trials for advanced esophageal adenocarcinoma [3]. The choice of F127/P123 coformulation has been dictated by its widespread use in pharmaceutical preparations. Our system is a formulation different from those in use in the clinical trials. It is a mixed system of pluronics (F127/P123) and sodium cholate (NaC), that should drive the drug solubilization in the apolar inner compartment of pluronic micelles [4]. The screen provided by the pluronic/NaC mixed micelles should possibly slow down the degradation of the drug, thus enhancing its anticancer efficacy. These new systems could hopefully be used for different targets expanding the clinical applications. Moreover the use of pluronics has been suggested as a help to overcome multiple drug resistance (MDR) phenomena in antineoplastic therapy due to the ability to promote active membrane transport and increase the circulation time of the drug.
[1] A.M. Bodratti, P. Alexandridis, Formulation of poloxamers for drug delivery, J. Funct. Biomater. 9 (2018) 11.
[2] K. Knop, R. Hoogenboom, D. Fischer, U.S. Schubert, Poly(ethylene glycol) in drug delivery: pros and cons as well as potential alternatives, Angew. Chem. ¿Int. Ed. 49 (2010) 6288¿6308.
[3] A. Pitto-Barry, N.P.E. Barry, Pluronic block-copolymers in medicine: from chemical and biological versatility to rationalisation and clinical advances, Polym. Chem. 5 (2014) 3291¿3297.
[4] E.Tasca, A. Del Giudice, L. Galantini, K. Schillén, A. M. Giuliani, M. Giustini. A fluorescence study of the loading and time stability of doxorubicin in sodium cholate/PEO-PPO-PEO triblock copolymer mixed micelles. J. Colloid Interf. Sci., 540 (2019) 593-601.