Towards Universal Stimuli-Responsive Drug Delivery Systems: Pillar[5]arenes Synthesis and Self-Assembly into Nanocontainers with Tetrazole Polymers.

Dmitriy N Shurpik,Valeriy N Kizhnyaev,Olga A Mostovaya,Daut R Islamov,Konstantin S Usachev,Lyaysan I Makhmutova,Anastasia A Nazarova,Ivan I Stoikov

doi:10.3390/nano11040947

Dmitriy N Shurpik, Valeriy N Kizhnyaev + Show 6 more

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https://doi.org/10.3390/nano11040947

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Abstract

In this work, we have proposed a novel universal stimulus-sensitive nanosized polymer system based on decasubstituted macrocyclic structures—pillar[5]arenes and tetrazole-containing polymers. Decasubstituted pillar[5]arenes containing a large, good leaving tosylate, and phthalimide groups were first synthesized and characterized. Pillar[5]arenes containing primary and tertiary amino groups, capable of interacting with tetrazole-containing polymers, were obtained with high yield by removing the tosylate and phthalimide protection. According to the fluorescence spectroscopy data, a dramatic fluorescence enhancement in the pillar[5]arene/fluorescein/polymer system was observed with decreasing pH from neutral (pH = 7) to acidic (pH = 5). This indicates the destruction of associates and the release of the dye at a pH close to 5. The presented results open a broad range of opportunities for the development of new universal stimulus-sensitive drug delivery systems containing macrocycles and nontoxic tetrazole-based polymers.

Highlights

In recent years, the pharmaceutical industry has had an increasing interest in the development and methods of introducing nanosystems in the treatment of various diseases by encapsulating drugs in biocompatible polymer matrices [1,2,3]
The two most studied tetrazole-containing polymers were selected as objects of this study, namely, poly-5-vinyltetrazole (PVT) and polyvinyl ethyl ether (PVTE)
The polymers used in drug delivery systems (DDSs) and containing carboxylate groups (Nisopropylacrylamide (NIPAM), poly(alkyl acrylic acid)s, modified poly(glycidol)s (PGs)) do not penetrate into the cell due to the submicron size, but they are fixed on the surface [44]

Summary

Introduction

The pharmaceutical industry has had an increasing interest in the development and methods of introducing nanosystems in the treatment of various diseases by encapsulating drugs in biocompatible polymer matrices [1,2,3]. The polymer shell protects the loaded drug from premature biotransformation and can transport the drug to the focus of the disease practically without damage [1]. Water-soluble polymer systems occupy a special place among such drug delivery systems (DDSs) [4,5]. Polymer systems have a number of disadvantages, namely, an extremely developed spatial structure and weak receptor properties, which complicate their controlled interaction with drugs [8,9]

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Conclusion