Advanced Control of Drug Delivery for In Vivo Health Applications via Highly Biocompatible Self-Assembled Organic Nanoparticles

Abstract

The use of nanostructured materials for targeted and controlled delivery of bioactive molecules is an attractive alternative to conventional drug administration protocols, enabling selective targeting of diseased cells, lower administered dosages, and reduced systemic side effects. Although a variety of nanocarriers have been investigated in recent years, electroactive organic polymer nanoparticles present several exciting advantages. Here we demonstrate that thin films created from nanoparticles synthesized from violanthrone-79, an n-type semiconducting organic material, can incorporate and release dexamethasone in vitro in a highly controlled manner. By systematically altering the nanoparticle formation chemistry, we successfully tailored the size of the nanoparticles between 30 and 145 nm to control the initial amount of drug loaded into the organic particles. The biocompatibility of the different particles was tested using live/dead assays of dorsal root ganglion neurons isolated and cultured from mice, revealing that elevated levels of the sodium dodecyl sulfate surfactant used to create the smaller nanoparticles are cytotoxic; however, cell survival rates in nanoparticles larger than 45 nm exceed 86% and promote neurite growth and elongation. By manipulating the electrical stimulus applied to the electroactive nanoparticle films, we show an accelerated rate of drug release in comparison to passive release in aqueous media. Furthermore, pulsing the electrical stimulus was successfully used to selectively switch the accelerated release rate on and off. By combining the tuning of drug loading (through tailored nanoparticle synthesis) and drug release rate (through electrical stimulus protocols), we demonstrate a highly advanced control of drug delivery dosage in a biocompatible delivery vehicle. This work highlights the significant potential of electroactive organic nanoparticles for implantable devices that can deliver corticosteroids directly to the nervous system for the treatment of inflammation associated with neurological disorders, presenting a translatable pathway toward precision nanomedicine approaches for other drugs and diseases.

Design Parameters and Human Biocompatibility Assessment Protocols for Organic Semiconducting Neural Interfaces: Toward a Printed Artificial Retina with Color Vision

“…A) Previously reported absorbance spectra of human photoreceptors. [ 37 ] B) Comparison of S cone absorbance spectrum with film and solution absorbance spectra for F8T2 and PC 61 BM materials. C) Comparison of M cone absorbance spectrum with film and solution absorbance spectra for P3HT and SF‐PDI materials.…”

“…Light-induced neuromodulation can be achieved in several different manners, including direct activation via near-infrared light, optogenetics, or optoelectronic neural interfaces. [37] Of these approaches, optoelectronic interfaces have proven the most versatile, since chemically modifying the primary materials to tune the performance in specific wavelength ranges is straightforward and the device architecture can also be readily adapted to meet the needs of a wide range of applications. Previous work exploring the interfacing of organic semiconductors with neuronal cells indicates that the transfer of absorbed energy from the semiconductor to the biological cells can proceed via either photothermal, [38] photofaradaic, [39][40][41] or photocapacitive [20][21][22][23][24] mechanisms to either depolarize or hyperpolarize neurons.…”

“…Optical absorbance spectra of organic semiconductor solutions and films compared to previously reported spectra of human photoreceptors. A) Previously reported absorbance spectra of human photoreceptors [37]. B) Comparison of S cone absorbance spectrum with film and solution absorbance spectra for F8T2 and PC 61 BM materials.…”

Molecular electronics: an Australian perspective

“…Adelaide, Jingxian Yu Electrochemical impedance spectroscopy ARC [ 133] Curtin, Simone Ciampi Attoamper current, dielectric, lock-in techniques, charge measurements (down to picocoulomb), life-time semiconductor charge carriers measurements ARC [ 107,143,264,265] Curtin, Nadim Darwish, Simone Ciampi Electrochemical impedance spectroscopy ARC [ 203,266] Macquarie, Koushik Venkatesan Luminescent biosensors SNSF [ 267] Sydney, Maxwell Crossley Molecular biosensors [268][269][270][271] Sydney, Matthew Griffith Patch clamp electrophysiology, electrochemical impedance spectroscopy ARC, NHMRC [ 134,[272][273][274] synthetic chemistry of peptides, nanomaterials, metal complexes, organic functional units including switches and connectors, and light absorbers, emitters and upconverters.…”