Preparation, characterisation and in vitro and in vivo evaluation of CD44-targeted chondroitin sulphate-conjugated doxorubicin PLGA nanoparticles.


Institute of Pharmacology, School of Pharmaceutical Sciences, Shandong Key Laboratory of Cerebral Microcirculation, Taishan Medical University, Taian 271000, Shandong, China. Electronic address: [Email]


The purpose of this study was to ascertain the effect of chondroitin sulphate-modified doxorubicin (Dox) nanoparticles on enhancing the tumour-targeting effect and tumour growth inhibition effect of doxorubicin both in vitro and in vivo. The chondroitin sulphate-doxorubicin conjugate and its poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CS-Dox-PLGA) were successfully synthesised, and then characterized by Fourier-transform infrared spectroscopy (FTIR), proton magnetic resonance (1HNMR), thermogravimetric analysis/differential scanning calorimetry (TGA/DSC), transmission electron microscope (TEM), zeta potential and laser light scattering. Taking advantage of the enhanced permeability and CD44-mediated endocytosis, CS-Dox-PLGA showed excellent capacity for penetrating the peripheral tumour barrier and into the nucleus of tumour cells. The CS-Dox-PLGA cellular uptake was improved and exhibited a significantly higher level of cytotoxicity in U251 cells. After intravenous administration, the CS-Dox-PLGA showed good pharmacokinetic properties and excellent U251-induced tumour inhibition with low cardiac toxicity. Therefore, CS-Dox-PLGA with low cardiac toxicity and good anti-tumour ability might be a better choice for Dox in clinical practice.


Biodistribution,CD44 targeting,Chondroitin sulphate,Doxorubicin,Pharmacokinetics,Poly(lactic-co-glycolic acid),

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