0000000000299296
AUTHOR
Elisamaria Tasca
Poloxamer/sodium cholate co-formulation for micellar encapsulation of Doxorubicin with high efficiency for intracellular delivery: an in-vitro bioavailability study
Abstract Hypothesis Doxorubicin hydrochloride (DX) is widely used as a chemotherapeutic agent, though its severe side-effects limit its clinical use. A way to overcome these limitations is to increase DX latency through encapsulation in suitable carriers. However, DX has a high solubility in water, hindering encapsulation. The formulation of DX with sodium cholate (NaC) will reduce aqueous solubility through charge neutralization and hydrophobic interactions thus facilitating DX encapsulation into poloxamer (F127) micelles, increasing drug latency. Experiments DX/NaC/PEO-PPO-PEO triblock copolymer (F127) formulations with high DX content (DX-PMs) have been prepared and characterized by scat…
A Stereochemically Driven Supramolecular Polymerisation
Anthracyclines self-assemble in water into dimers. In the presence of sufficiently high salt (NaCl) concentrations, solutions of the antibiotic doxorubicin, but not those of the closely related molecules daunomycin and epirubicin, turn into gels barely compatible with the presence of small oligomers. The use of spectroscopic, scattering, imaging and computational techniques, allowed light to be shed on the self-assembly process that triggered doxorubicin gelification. A complex picture emerged, with doxorubicin molecules assembled into long, highly chiral, supramolecular aggregates made of hundreds of units, showing redshifted fluorescence spectra, very short fluorescence lifetimes and smal…
The self-association equilibria of doxorubicin at high concentration and ionic strength characterized by fluorescence spectroscopy and molecular dynamics simulations
Abstract The self-association equilibria of doxorubicin hydrochloride (DX), at high drug and NaCl concentrations, are studied by temperature scan fluorescence spectroscopy, with the support of molecular dynamics (MD) calculations. Even though all anthracyclines show dimerization equilibria, DX only can further associate into long polymeric chains according to DXmon ⇄ DXdim ⇄ DXpol. This is reflected not only in the mechanical properties of DXpol solutions (behaving as thixotropic gels) but also in their spectroscopic behaviour. Fluorescence, in particular, is the technique of election to study this complex set of equilibria. Upon increasing the temperature, DXpol melts into DXdim, which in …
A fluorescence study of the loading and time stability of doxorubicin in sodium cholate/PEO-PPO-PEO triblock copolymer mixed micelles
Abstract Hypothesis Doxorubicin hydrochloride (DX) is one of the most powerful anticancer agents though its clinical use is impaired by severe undesired side effects. DX encapsulation in nanocarrier systems has been introduced as a mean to reduce its toxicity. Micelles of the nonionic triblock copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) (PEO-PPO-PEO), are very promising carrier systems. The positive charge of DX confines the drug to the hydrophilic corona region of the micelles. The use of mixed micelles of PEO-PPO-PEO copolymers and a negatively charged bile salt should favour the solubilization of DX in the apolar core region of the micelles. Experiments We st…