Encapsulation of antitumor copper coordination compounds into liposomes
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Lomonosov Moscow State University, Moscow, Russia
Publication date: 2021-09-27
Public Health Toxicol 2021;1(Supplement Supplement 1):A14
Medation is an antitumor drug classified as a copper complex compound of organic ligand containing 2-alkylthioimidasolone. According to the results of pre-clinical trials, the drug is recommended for Triple-Negative Breast Cancer treatment. Nevertheless, a significant limitation for in vivo use of this complex is its hydrophobic properties and, as a result, a low level of bioavailability. One of the ways to increase bioavailability of hydrophobic substances is their encapsulation into drug delivery systems. Liposomes are the most studied and well-described systems for biological substances delivery. Hydrophobic properties of our coordination compound do not allow us to use typical ways of encapsulation. Thus, the main aim of our work is to investigate for an optimal method for encapsulation of copper coordination compound into liposomes.
We have developed an approach for copper complex encapsulation into liposomes, which is realized by injection of organic solvents mixture into copper salt solution. Liposomes were prepared from dipalmitoylphosphatidylcholine (DPPC), cholesterol (Chol) and PEG-distearoylphosphoethanolamine (DSPE-PEG(2000)) in the ratio DPPC:Cholesterol:DSPE-PEG (2000) 55:40:5. The presence of complex in liposomes has been proven by absorption spectra, quantitative complex determination was performed by HPLC. This approach allowed us to obtain colloidal stable suspension, loading capacity in molar complex to lipid ratio was up to 1,22%.
For obtained suspension we have estimated storage stability in 0,9% NaCl solution at 4oС, loading capacity was preserved up to one month. Liposomal suspension can be concentrated up to required values, the properties are retained in conditions close to blood flow (DMEM media, 37oС). We found that copper complex is included into lipid bilayer, localization has been studied under various conditions. Cytotoxicity and biocompatibility of liposomal formulation was estimated by MTT-test on MCF-7 cell line. The obtained liposomal formulation showed greater cytotoxicity in comparison with pure drug, which confirms the prospects for practical application.
The developed approach was used for encapsulation of copper coordination compounds similar to mediation, loading capacity values were of the same order as for the model complex.
This work was supported by RSF grant 19-74-10059 and MSU Program of Development.
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