Development of pH-Sensitive Drug Carriers for Improved Therapeutic Efficacy: In Vitro and In Vivo Evaluation
Kuznetsov A. O.1, Vlasicheva Yu. N.2, Lengert E. V.1, Ermakov A. V.1,3
1 Institute of Molecular Theranostics, I.M. Sechenov First Moscow State Medical University, 8 Trubetskaya Str., 119991 Moscow, Russia
2 D.I. Mendeleyev University of Chemical Technology of Russia, Miusskaya square, 9, building 6, Moscow, 125047 Russia
3 Life Improvement by Future Technologies (LIFT) Center, 143025 Moscow, Russia
Abstract
The targeted delivery of pharmaceuticals to specific sites within the human body remains a significant challenge in modern medicine. Conventional pH-sensitive drug delivery systems have demonstrated poor clinical performance due to their inability to effectively navigate the complex physiological environment. This study aims to address this limitation by developing a novel pH-sensitive drug carrier system that exhibits enhanced stability and improved therapeutic efficacy. We have designed a unique pH-responsive polymeric nanoparticle platform that is capable of selectively releasing the encapsulated drug payload in response to the slightly acidic microenvironment characteristic of solid tumours. The physicochemical properties of the nanoparticles, including size, surface charge, and drug-loading capacity, were thoroughly investigated and optimised. In vitro studies confirmed the pH-dependent drug release kinetics and the enhanced cytotoxicity of the drug-loaded nanoparticles against cancer cell lines compared to the free drug. Furthermore, in vivo experiments conducted in an animal model of solid tumours demonstrated the superior anti-tumour efficacy of the pH-sensitive drug delivery system, with a significant reduction in tumour volume and improved animal survival rates. These findings suggest that this innovative pH-responsive drug carrier system holds great promise for the targeted treatment of solid malignancies and other diseases characterised by altered pH microenvironments.
The study was supported by the grant of the RUSSIAN SCIENTIFIC FUND No. 22-73-10032,
https://rscf.ru/project/22-73-10032/
Speaker
Alexey V. Ermakov
Institute of Molecular Theranostics, I.M. Sechenov First Moscow State Medical University
Russia
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