Cell Responses to Electrical Pulse Stimulation for Anticancer Drug Release.

Anna Puiggalí-Jou,Luis J Del Valle,Carlos Alemán

doi:10.3390/ma12162633

Anna Puiggalí-Jou, Luis J Del Valle + Show 1 more

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https://doi.org/10.3390/ma12162633

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Abstract

Electrical stimulation is an attractive approach to tune on-demand drug release in the body as it relies on simple setups and requires typically 1 V or less. Although many studies have been focused on the development of potential smart materials for electrically controlled drug release, as well as on the exploration of different delivery mechanisms, progress in the field is slow because the response of cells exposed to external electrical stimulus is frequently omitted from such investigations. In this work, we monitor the behavior of prostate and breast cancer cells (PC-3 and MCF7, respectively) exposed to electroactive platforms loaded with curcumin, a hydrophobic anticancer drug. These consist in conducting polymer nanoparticles, which release drug molecules by altering their interactions with polymer, and electrospun polyester microfibres that contain electroactive nanoparticles able to alter the porosity of the matrix through an electro-mechanical actuation mechanism. The response of the cells against different operating conditions has been examined considering their viability, metabolism, spreading and shape. Results have allowed us to differentiate the damage induced in the cell by the electrical stimulation from other effects, as for example, the anticancer activity of curcumin and/or the presence of curcumin-loaded nanoparticles or fibres, demonstrating that these kinds of platforms can be effective when the dosage of the drug occurs under restricted conditions.

Highlights

On-demand local delivery of drug molecules to target tissues provides a means for effective drug dosing, fulfilling requirements for a variety of therapeutic applications while reducing the adverse effects of systemic drug delivery [1,2,3,4]
Cells have been seeded onto the anode surface and, initially, our efforts have been devoted to identify the optimal potential difference for therapies based on the controlled release of drugs with the intention of not damaging healthy tissues
Voltage-induced cell death assays have been carried out using PC-3 cells seeded on a simple metal substrate that is a representative working electrode among those used for bioelectrical stimulation therapies

Summary

Introduction

On-demand local delivery of drug molecules to target tissues provides a means for effective drug dosing, fulfilling requirements for a variety of therapeutic applications while reducing the adverse effects of systemic drug delivery [1,2,3,4]. Pulsatile electrically stimulated drug delivery devices have drawn attention because they allow repeatable and reliable drug release flux for clinical needs and because of their simplicity and versatility. Various types of electrically modulated devices for drug release, such as hydrogel [6,7,8,9], nanoparticles [10,11,12,13], membranes [14,15] and fibres [16,17,18,19] have been reported in literature. Electrical stimulation has been employed in clinics for its potential beneficial effects to revive damaged tissues in the neuromuscular system, reduce the progression of diseases related to the bones such as osteoarthritis and osteonecrosis [20], to reduce pain [21] or to favorably treat Parkinson’s disease [22].

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