Supramolecular Amphiphiles Based on Pillar[5]arene and Meroterpenoids: Synthesis, Self-Association and Interaction with Floxuridine.

Alan A Akhmedov,Dmitriy N Shurpik,Pavel L Padnya,Denis Yu Grishaev,Rustem R Gamirov,Yulia V Panina,Alena I Khadieva,Vitaliy V Plemenkov,Asiya F Gazizova,Ivan I Stoikov

doi:10.3390/ijms22157950

Alan A Akhmedov, Dmitriy N Shurpik + Show 8 more

Open Access

https://doi.org/10.3390/ijms22157950

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Abstract

In recent years, meroterpenoids have found wide biomedical application due to their synthetic availability, low toxicity, and biocompatibility. However, these compounds are not used in targeted drug delivery systems due to their high affinity for cell membranes, both healthy and in cancer cells. Using the approach of creating supramolecular amphiphiles, we have developed self-assembling systems based on water-soluble pillar[5]arene and synthetic meroterpenoids containing geraniol, myrtenol, farnesol, and phytol fragments. The resulting systems can be used as universal drug delivery systems. It was shown by turbidimetry that the obtained pillar[5]arene/synthetic meroterpenoid systems do not interact with the model cell membrane at pH = 7.4, but the associates are destroyed at pH = 4.1. In this case, the synthetic meroterpenoid is incorporated into the lipid bilayer of the model membrane. The characteristics of supramolecular self-assembly, association constants and stoichiometry of the most stable pillar[5]arene/synthetic meroterpenoid complexes were established by UV-vis spectroscopy and dynamic light scattering (DLS). It was shown that supramolecular amphiphiles based on pillar[5]arene/synthetic meroterpenoid systems form monodisperse associates in a wide range of concentrations. The inclusion of the antitumor drug 5-fluoro-2′-deoxyuridine (floxuridine) into the structure of the supramolecular associate was demonstrated by DLS, 19F, 2D DOSY NMR spectroscopy.

Highlights

Nowadays researchers are paying more and more attention to natural compounds and their analogues [1,2]
We propose and develop a synthetic non-covalent self-assembling system of supramolecular amphiphiles based on “host-guest” complexes of pillar[5]arene and meroterpenoids as a universal drug delivery system (DDS)
The pillar[5]arene can act as a water-soluble component, and the meroterpenoid fragment can act as a lipophilic fragment

Summary

Introduction

Nowadays researchers are paying more and more attention to natural compounds and their analogues [1,2]. The main difficulty of using archaeosomes in targeted delivery is their interaction with cells and excessively rapid release of the delivered substrate [8,11] In this regard, the development of a new generation of archeosomes capable of providing targeted delivery of therapeutic agents is an interesting and worthwhile task. Pillar[5]arene complexes with charged pyridinium [17] or imidazolium [18] salts can be built according to the “host-guest” principle The presence of these properties opens up new opportunities in the formation of vesicles, transmembrane artificial channels, nanoreactors, metal-organic frameworks, liquid crystals, and supramolecular polymers [19]. We propose and develop a synthetic non-covalent self-assembling system of supramolecular amphiphiles based on “host-guest” complexes of pillar[5]arene and meroterpenoids as a universal drug delivery system (DDS)

Results and Discussion

Determination of the Hydrodynamic Particle Size by Dynamic Light Scattering

Measurement of the Zeta-Potential

Turbidimetry

Conclusions