Příprava polymerních nanoléčiv pomocí mikrofluidní nanoprecipitace - vlastnosti in vitro a in vivo za simulovaných fyziologických podmínek

Vragović, Martina

This doctoral thesis is concerned with the development of stimuli-responsive polymer-based drug- delivery systems and with the relationship between macromolecular design and therapeutic performance under simulated physiological conditions and in vivo. A series of complementary nano- and microscale platforms was prepared by means of RAFT polymerization, solid-phase synthesis, and microfluidic fabrication. Particular attention was paid to the influence of polymer composition, chain architecture, morphology, and environmental responsiveness on drug loading, colloidal stability, triggered release, membrane interaction, biodistribution, and biological activity. The first part of the work investigates doxorubicin-loaded polymersomes bearing identical PHPMAm coronas but differing in membrane chemistry. These systems were used to assess how the nature of the stimulus-responsive block affects release behaviour and therapeutic outcome. Among the formulations studied, pH-responsive PHPMAm-b-PDPA polymersomes exhibited high stability at physiological pH and pronounced cargo release under mildly acidic conditions, which was reflected in superior antitumour efficacy, prolonged survival, and good tolerability in murine models when compared with ROS-responsive and non-responsive analogues. The second part...

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