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Fluoropolymers with “Fluorine Magic”

Developing effective and safe delivery vehicles for medically important biomacromolecules is a key challenge in modern drug research. Fluoropolymers have emerged as a modular solution to this challenge, and a new study in the journal Medicine in Drug Discovery has explored these drug delivery systems.

Study: Fluoropolymers-mediated efficient biomacromolecule drug delivery. Image Credit: Sadovnikova Olga/Shutterstock.com

Biomacromolecule Drugs

A key focus in current medical research, biomacromolecule drugs are categorized by their large size and complex structures. This class of drugs includes proteins, peptides, and nucleic acids and possess significant advantages to conventional, small-molecule drugs. Advantages of biomacromolecules include higher specificity, biocompatibility, potency, and enhanced targeting of diseases.

Due to their advantageous properties, biomacromolecule drugs have been widely studied for the treatment of immune diseases, cancers, neurodegenerative diseases, and cardiovascular diseases, as well as vaccine delivery. However, these drugs are not without their challenges, which are due to their complex structure and large size. Biomacromolecule drugs suffer from intrinsic instability and an inability to cross barriers such as cell membranes, extracellular barriers, and intracellular barriers.

Developing Delivery Systems for Biomacromolecule Drugs

Because of the challenges associated with biomacromolecule drugs, multivariate drug delivery systems have been widely explored over the past two decades. The ideal drug delivery system requires properties such as high bioavailability, a precise therapeutic and curative effect, and reduced side effects for the targeted, site-specific delivery of therapies.

In recent years, polymers, especially polyethyleneimine, have emerged as forerunners in this field of research. In fact, polyethyleneimine has emerged as a gold standard for measuring the effectiveness of other carriers. Whilst research into polymers as drug delivery systems has proven promising, there are still issues with them, including increased cytotoxicity and problems with gene release during delivery.

To overcome these issues, there has been significant research into synthetic polymer chemistry and coupling technologies.

Fluorine Magic and Fluoropolymers

Materials that possess “fluorine magic” exhibit unusual behaviors and physiochemical and biological effects compared to their nonfluorinated analogs. This is due to the replacement of hydrogen atoms by fluorine atoms. These unusual and unique material properties are determined by the molecular structure and intermolecular interactions of the fluorinated materials.

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Fluorine is an unusual element that is close to hydrogen in size but possesses the highest electronegativity of all elements. When fluorine bonds with carbon, it creates a highly polarized bond, and, moreover, the C-F bond is the strongest single bond in organic chemistry. Due to these unique properties, fluorine and fluorine-containing groups can be advantageous for drug delivery, conferring advantages such as improved metabolic stability, enhanced membrane permeation, and superior binding affinity.

This has become an important strategy, with over 25% of all current pharmaceutical products containing fluorine atoms. Recently, there has been increased research focus on including fluorine atoms in polymers to created fluoropolymers. Fluoropolymers exhibit low surface energy and biological and chemical inertness.

Fluoropolymers have enhanced structural stability, reduced cytotoxicity, and enhanced transmembrane abilities. Moreover, recent research into grafting fluoroalkyl chains onto polymers has demonstrated novel properties such as self-assembly.

The Study

The pre-proof paper has investigated recent advances in research into fluoropolymers for the delivery of biomacromolecule drugs. Properties, synthesis, assembly, and benefits of these unique drug delivery systems have been discussed in detail.

Primary advantages have been identified by the authors for the delivery of biomacromolecule drugs using fluoropolymers. These are superior self-assembly abilities, stable complex formation driven by hydrophobic, electrostatic, and fluorine effects, enhanced stability in serum, reduced interaction with proteins and enzymes in serums, endocytosis, and endosomal escape efficiency promotion, and reduced cytotoxicity.

Current research into gene therapy with fluoropolymer delivery systems has demonstrated advantages such as increased transfection efficiency due to properties such as augmenting the stability of drugs, increased serum tolerance, and enhanced intracellular release.

However, the authors have identified that challenges exist with using fluoropolymers. These include the in vivo metabolism and degradability of these polymers. Moreover, aggregates can proliferate in vivo, leading to safety concerns such as effects on liver metabolism.

One solution to this issue presented in the research is the introduction of stimulus-specific side chains. Furthermore, compared to gene therapy, the delivery of proteins and peptides is problematic due to their large size, complex surface charges, and post-delivery activity maintenance.

The paper includes a discussion of the application of this novel drug delivery strategy in cancer treatment, including tumor vaccine delivery, and further explores the challenges and future prospects for fluoropolymer biomacromolecule drug delivery, aiming to facilitate further development in this field of biomedical research. Based on the results of their review, the authors have concluded that fluoropolymers will play a key role in biomedical applications such as immunotherapy and gene editing.

Further Reading

Song, T et al. (2022) Fluoropolymers-mediated efficient biomacromolecule drug delivery [pre-proof] Medicine in Drug Delivery 2022: 100123 | sciencedirect.com. Available at: https://www.sciencedirect.com/science/article/pii/S2590098622000045

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Reginald Davey

Written by

Reginald Davey

Reg Davey is a freelance copywriter and editor based in Nottingham in the United Kingdom. Writing for News Medical represents the coming together of various interests and fields he has been interested and involved in over the years, including Microbiology, Biomedical Sciences, and Environmental Science.

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