Abstract
Introduction. The use of the anticancer drug paclitaxel is limited due to its high toxicity and lipophilicity. A new polymer composition of paclitaxel has been proposed, which provides targeted transport of the drug into tumor cells and improves its safety.Aim. Method development for preparation of a novel paclitaxel formulation consisting of a conjugate of PLGA nanoparticles with the third domain of alpha-fetoprotein.Materials and methods. The object of this study is paclitaxel-loaded nanoparticles based on a copolymer of lactic and glycolic acids, the surface of which is modified with a vector molecule - the recombinant third domain of alpha-fetoprotein. Nanoparticles were obtained by single emulsification method and precipitation. Conjugation with a protein molecule was performed by the carbodiimide method. The analysis of the obtained nanoparticles was carried out using dynamic and electrophoretic light scattering, high performance liquid chromatography, dialysis membrane method.Results and discussion. Synthesis of paclitaxel-loaded nanoparticles based on a copolymer of lactic and glycolic acids and its conjugation optimization under varying a wide range of conditions have been carried out. The resulting conjugate had an average diameter of 280 ± 12 nm. The conjugation efficiency was 95 %. The release of paclitaxel from the polymer matrix in the release medium was 65 % in 220 h.Conclusions. A method of obtaining and substantiating the composition of the original nanosized form of paclitaxel is proposed. The possibility of prolonged release of paclitaxel from the polymer matrix has been shown.
Highlights
The use of the anticancer drug paclitaxel is limited due to its high toxicity and lipophilicity
Method development for preparation of a novel paclitaxel formulation consisting of a conjugate of PLGA nanoparticles with the third domain of alpha-fetoprotein
The object of this study is paclitaxel-loaded nanoparticles based on a copolymer of lactic and glycolic acids, the surface of which is modified with a vector molecule – the recombinant third domain of alpha-fetoprotein
Summary
The use of the anticancer drug paclitaxel is limited due to its high toxicity and lipophilicity. Aim. Method development for preparation of a novel paclitaxel formulation consisting of a conjugate of PLGA nanoparticles with the third domain of alpha-fetoprotein. Ранее в нашей лаборатории была показана возможность получения наночастиц PLGA с паклитакселом и дальнейшей модификации их поверхности рекомбинантным третьим доменом AFP человека (rAFP3d) [9, 10].
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