Nanobiotechnology for health-care

Drug delivery with pH-sensitive star-like Dextran-Graft Polyacrylamide copolymer

S. Ponomarenko1, A. Grebinnyk2, S. Prylutska3, S. Grebinnyk2, 
V. Chumachenko1, N. Kutsevol1, Yu. Prylutskyy1, M. Frohme2

1Taras Shevchenko National University of Kyiv, Volodymyrska Str., 64, 01601 Kyiv, Ukraine. E-mail: prylut@ukr.net
2Technical University of Applied Sciences Wildau, Hochschulring 1, 15745 Wildau, Germany.
3National University of Life and Environmental Science of Ukraine, Heroiv Oborony Str., 15, 03041 Kyiv, Ukraine.

Polymer nanoparticles represent one of the innovative non-invasive approaches for drug delivery applications in cancer therapy. In this study, the star-like dextran-graft-polyacrylamide (D-g-PAA) copolymer in anionic form (D-g-PAAan) was developed for the pH-triggered targeted drug delivery of the common chemotherapeutic drugs – Doxorubicin (Dox) and Cisplatin (Cis). The monodisperse size distribution of both Dox- and Cis-loaded polymeric nanoparticles was estimated at 80 nm. The acidification of the buffer from pH 7.4 to 5.0 promoted release of Dox and Cis on 26.0 and 32.5% at 48 h, respectively (Figure). D-g-PAAan nanoparticles increased toxic potential of the drugs against human and mouse lung carcinoma cells (A549 and LLC), but not against normal human lung cells (HEL299). The drug-loaded D-g-PAAan-nanoparticles promoted further oxidative stress and apoptosis induction in LLC cells by increasing intracellular ROS generation and activation of caspase 3/7. The data obtained indicate that the strategy of chemotherapeutic drugs encapsulation within the branched D-g-PAAan nanoparticle allows not only to realize pH-triggered drug release but also to potentiate its cytotoxic, prooxidant and proapoptotic effects against lung carcinoma cells in vitro. 

Figure. Drug release from D-g-PAAan nanoparticles: schematic representation of Dox (a) and Cis (c) release; cumulative release of Dox (b) and Cis (d) during 48 h of incubation at pH 7.4 and 5.0.