Alkyl Chain Length in Poly(2-oxazoline)-Based Amphiphilic Gradient Copolymers Regulates the Delivery of Hydrophobic Molecules: A Case of the Biodistribution and the Photodynamic Activity of the Photosensitizer Hypericin
| Autor: | Daniel Jancura, Pavol Miškovský, Barbora Kundeková, Mariana Máčajová, Lenka Lenkavska, Boris Bilčík, Juraj Kronek, Veronika Huntosova, Annamária Jutková, Ivan Čavarga, Shubhashis Datta |
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| Rok vydání: | 2021 |
| Předmět: |
Anthracenes
Biodistribution Photosensitizing Agents Polymers and Plastics Chemistry Polymers Comonomer Bioengineering Hypericin Biomaterials chemistry.chemical_compound Photochemotherapy Drug delivery Amphiphile Materials Chemistry Biophysics Side chain Nanoparticles Photosensitizer Tissue Distribution Gradient copolymers Oxazoles Perylene |
| Zdroj: | Biomacromolecules. 22(10) |
| ISSN: | 1526-4602 |
| Popis: | Self-assembled nanostructures of amphiphilic gradient copoly(2-oxazoline)s have recently attracted attention as promising delivery systems for the effective delivery of hydrophobic anticancer drugs. In this study, we have investigated the effects of increasing hydrophobic side chain length on the self-assembly of gradient copolymers composed of 2-ethyl-2-oxazoline as the hydrophilic comonomer and various 2-(4-alkyloxyphenyl)-2-oxazolines as hydrophobic comonomers. We show that the size of the formed polymeric nanoparticles depends on the structure of the copolymers. Moreover, the stability and properties of the polymeric assembly can be affected by the loading of hypericin, a promising compound for photodiagnostics and photodynamic therapy (PDT). We have found the limitation that allows rapid or late release of hypericin from polymeric nanoparticles. The nanoparticles entering the cells by endocytosis decreased the hypericin-induced PDT, and the contribution of the passive process (diffusion) increased the probability of a stronger photoeffect. A study of fluorescence pharmacokinetics and biodistribution revealed differences in the release of hypericin from nanoparticles toward the quail chorioallantoic membrane, a preclinical model for in vivo studies, depending on the composition of polymeric nanoparticles. Photodamage induced by PDT in vivo well correlated with the in vitro results. All formulations studied succeeded in targeting hypericin at cancer cells. In conclusion, we demonstrated the promising potential of poly(2-oxazoline)-based gradient copolymers for effective drug delivery and sequential drug release needed for successful photodiagnostics and PDT in cancer therapy. |
| Databáze: | OpenAIRE |
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