Electroactive Polymers for On-Demand Drug Release

Abstract

Conductive materials have played a significant role in advancing society into the digital era. Such materials are able to harness the power of electricity and are used to control many aspects of daily life. Conductive polymers (CPs) are an emerging group of polymers that possess metal-like conductivity yet retain desirable polymeric features, such as processability, mechanical properties, and biodegradability. Upon receiving an electrical stimulus, CPs can be tailored to achieve a number of responses, such as harvesting energy and stimulating tissue growth. The recent FDA approval of a CP-based material for a medical device has invigorated their research in healthcare. In drug delivery, CPs can act as electrical switches, drug release is achieved at a flick of a switch, thereby providing unprecedented control over drug release. In this review, recent developments in CP as electroactive polymers for voltage-stimuli responsive drug delivery systems are evaluated. The review demonstrates the distinct drug release profiles achieved by electroactive formulations, and both the precision and ease of stimuli response. This level of dynamism promises to yield “smart medicines” and warrants further research. The review concludes by providing an outlook on electroactive formulations in drug delivery and highlighting their integral roles in healthcare IoT.

Introduction

The digitization of healthcare has created a paradigm shift in the way healthcare is delivered, offering new opportunities. While some sectors have adopted the change quite successfully, for example, in the development of remote monitoring technologies such as wearable diagnostic and sensory devices, other sectors need further consideration including drug development. Traditional drug delivery systems (DDS), such as those administered orally or in injectables, have significantly contributed to the treatment of diseases, having a significant societal benefit. To give a therapeutic effect, drug molecules need to be released from the DDS and become available for interaction with the body. The typical pattern of drug release involves diffusion, erosion, or swelling, which rely on the passive release of the drug, and hence are preprogrammed.[1] In other words, once administered there is no further control over release characteristics.[2] Most of the presently available DDS are not able to deliver the drug in the required dose, to the target site, and within a specific time. Some of the disadvantages of this approach include side effects and toxicities.[3] Side effects and adverse drug effects are the most common concerns for medication safety. They mostly occur due to off-target drug action or higher doses contributing to medication noncompliance and nonadherence, and such practice raises concerns.[4] Thus, it is necessary to develop DDS with better safety and efficacy attributes. Furthermore, the discovery of new potent therapeutics such as biologics has increased the need for new, and sophisticated delivery systems. Understandably, a growing body of research has raised the importance of developing DDS with better control over drug release in which both the rate and the amount are precisely tailored to meet specific needs.

Recent advancements in material science have yielded state-of-the-art materials with organized structures and high performance; one important example is stimuli-responsive polymers. Such polymers have gained much interest from both academia and industry owing to their ability to mimic the behavior of living systems.[5] Stimuli-responsive polymers, also referred to as “smart” or “intelligent” polymers, exhibit chemical and/or physical alterations when subjected to internal or external stimuli.[6] These systems could be sensitive to single, dual, or multiple stimuli.[7] At the macromolecular level in the polymer chains, the changes may appear as bond cleavage, degradation, hydrophilic to hydrophobic equilibrium, and configuration.

Based on the stimuli’ nature, they can be classified into biological (e.g., enzymes and glucose), chemical (e.g., pH and redox), and physical (e.g., temperature, light, electrical field, and magnetic field),[8] Figure 1 highlights more examples of stimuli types. Hydrogels, micelles, and polymer-drug conjugates are classes of stimuli-responsive systems that have been researched for drug, anticancer, oral protein, and gene delivery.[9] Moreover, the release rate could be adjusted based on the changes in the delivery site microenvironment.[10] These systems hold numerous advantages such as precise control of drug release rate and triggered tuneable and targeted delivery, which is particularly important for the delivery of chemotherapeutics, anti-inflammatory drugs, psychotropic, and hormonal therapy.[11] Accordingly, they reduce the risk of unwanted side effects associated with off-target drug action and unnecessary high drug doses. Moreover, stimuli-responsive DDS can diminish the harmful “dose-dumping” effects of burst release.[12]

Electroactive materials are one class of stimuli-responsive systems that are garnering attention, partly galvanized by the recent FDA approval of a conductive polymer (CP)-based device.[14] Electricity has indeed been harnessed by society since the 1800s, but it is worth mentioning that nature has exploited electricity for longer. One salient example is the use of “bioelectricity” for maintaining normal physiological functions, such as neuronal signaling and muscle contraction.[15] In medicine, electric fields have been used in electroporation and iontophoresis to aid the drug molecules’ transport through membranes. Electric fields have been used directly as well in the treatment of tumors.[16] Thus, utilizing electric fields to trigger drug release from DDS is a tempting approach. For a DDS to be responsive to electrical stimulus, it must be conductive and allow electron transport.[17] While blending polymers with conductive fillers, for example, silver nanowires (Ag-NWs), carbon nanotubes (CNTs), and graphene can result in a conductive DDS,[18] intrinsic CPs are a collection of polymers that are already inherently conductive.[11] Conductive and electroactive are used interchangeably throughout this review to describe polymers with inherent conductive properties.

CPs have shown great potential to afford controlled and on-demand drug release. Previous reviews have discussed the early developments of CPs and this review will provide recent developments in electroactive DDS.[18] The following section details the mechanism by which CPs are controlled, which applies to the different CPs detailed herein. Thereafter, recent progress is presented for three of the most studied CPs for drug delivery which are polyethylenedioxythiophene (PEDOT), polypyrrole (PPy), and polyaniline (PANi). Compared to other CPs, PEDOT, PPy, and PANi are the most commonly used in drug delivery owing to their unique electrical and physicochemical properties.[19] They possess good biocompatibility, biodegradability, and low toxicity.[20] In addition, they have high surface area, good charge storage capacity, and high conductivity which make them suitable for the controlled release of drugs.[21] Moreover, they can be easily synthesized, and their properties can be tuned by changing the synthesis parameters. They are versatile and can be combined with other materials forming composites with tailored properties.[22] This review will highlight approaches that have been explored to overcome previously reported issues with such systems, including reduced sensitivity to stimulus, low drug loading capacity, and poor mechanical properties.[18] Furthermore, the fabrication process of such systems is also discussed. The final section will discuss the future outcomes, and how electroactive DDS can be integrated with other emerging technologies to synergistically advance developments in the field.

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Manal E. Alkahtani, Moe Elbadawi, Christopher A. R. Chapman, Rylie A. Green, Simon Gaisford, Mine Orlu, and Abdul W. Basit, Electroactive Polymers for On-Demand Drug Release

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Read also more on “Electroactive Polymers” in chapter 1 here:

• Conducting Polymers as Drug Release Systems