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Development and Evaluation of Stimuli-Responsive Chimeric Nanostructures

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Abstract

Chimeric/mixed stimuli-responsive nanocarriers are promising agents for therapeutic and diagnostic applications, as well as in the combinatorial field of theranostics. Herein, we designed chimeric nanosystems, composed of natural phospholipid and pH-sensitive amphiphilic diblock copolymer, in different molar ratios and assessed the polymer lyotropic effect on their properties. Initially, polymer-grafted bilayers were evaluated for their thermotropic behavior by thermal analysis. Chimeric liposomes were prepared through thin-film hydration and the obtained vesicles were studied by light scattering techniques, to measure their physicochemical characteristics and colloidal stability, as well as by imaging techniques, to elucidate their global and membrane morphology. Finally, in vitro screening of the systems’ toxicity was held. The copolymer effect on the membrane phase transition strongly depended on the pH of the surrounding environment. Chimeric nanoparticles were around and above 100 nm, while electron microscopy revealed occasional morphology diversity, probably affecting the toxicity of the systems. The latter was assessed to be tolerable, while dependent on the nanosystems’ material concentration, polymer concentration, and polymer composition. All experiments suggested that the thermodynamic and biophysical properties of the nanosystems are copolymer-composition- and concentration-dependent, since different amounts of incorporated polymer would produce divergent effects on the lyotropic liquid crystal membrane. Certain chimeric systems can be exploited as advanced drug delivery nanosystems, based on their overall promising profiles.

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Funding

This research has been financially supported by the General Secretariat for Research and Technology (GSRT) and the Hellenic Foundation for Research and Innovation (HFRI) (Scholarship Code: 392).

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Authors and Affiliations

  1. Section of Pharmaceutical Technology, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece

    Nikolaos Naziris, Natassa Pippa & Costas Demetzos

  2. Theoretical and Physical Chemistry Institute, National Hellenic Research Foundation, Athens, Greece

    Natassa Pippa, Varvara Chrysostomou & Stergios Pispas

  3. Biomedical Research Foundation, Academy of Athens, Athens, Greece

    Dimitris Stellas

  4. Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland, USA

    Dimitris Stellas

  5. Centre of Polymer and Carbon Materials, Polish Academy of Sciences, Zabrze, Poland

    Marcin Libera & Barbara Trzebicka

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  1. Nikolaos Naziris
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  2. Natassa Pippa
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  4. Varvara Chrysostomou
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Correspondence to Costas Demetzos.

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Electronic Supplementary Material

ESM 1

The stability evaluation of polydispersity, as well as diameters and wall dimensions extracted by cryo-TEM for the prepared chimeric nanosystems are provided in the supplementary material section. (DOCX 201 kb)

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Naziris, N., Pippa, N., Stellas, D. et al. Development and Evaluation of Stimuli-Responsive Chimeric Nanostructures. AAPS PharmSciTech 19, 2971–2989 (2018). https://doi.org/10.1208/s12249-018-1112-2

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