Physical approaches for drug delivery: an overview
01 Jan 2020-pp 161-190
TL;DR: This chapter mainly focuses on different physical drug-delivery techniques such as electroporation, optoporation, mechanopsoration, magnetoporation and hybrid techniques along with their working mechanisms, advantages, disadvantages, and limitations.
Abstract: Delivery of exogenous materials or cargo such as drugs, proteins, peptides, and nucleic acids into cells is a vital segment in molecular and cellular biology for potential cellular therapy and drug-discovery applications contributing toward personalization of medicine. Over the years, drug-delivery techniques have been developed in order to gain more control over the drug dosage, targeted delivery, and to minimize side effects. The major drug-delivery techniques can be classified as viral, chemical, and physical methods. Viral vectors are prominently used for gene therapy; however, they are cell-specific and have an immune response with high toxicity. Chemical methods are often limited by the low efficiency of plasmid delivery into different cell types due to plasmid degradation and toxicity. Considering these limitations, different physical methods such as photoporation, gene gun, hydrodynamic injection, electroporation, and mechanoporation, etc., are being widely developed for highly efficient cargo delivery with low toxicity. These methods are able to create transient hydrophilic membrane pores to deliver cargos into cells using different physical energies. Currently, ex vivo cargo delivery is widely studied while few in vivo applications have been developed. Concerning several obstacles to cargo delivery into cells, this chapter mainly focuses on different physical drug-delivery techniques such as electroporation, optoporation, mechanoporation, magnetoporation, and hybrid techniques along with their working mechanisms, advantages, disadvantages, and limitations. An insight into the future prospects and real-time applications of these techniques is also discussed.
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TL;DR: An in vivo method using a femtosecond laser to locally optoporate retinal ganglion cells (RGCs) targeted with functionalized gold nanoparticles (AuNPs) provides a novel, non-viral-based approach that has the potential to selectively target retinal cells in diseased regions while sparing healthy areas.
Abstract: Vision loss caused by retinal diseases affects hundreds of millions of individuals worldwide. The retina is a delicate central nervous system tissue stratified into layers of cells with distinct roles. Currently, there is a void in treatments that selectively target diseased retinal cells, and current therapeutic paradigms present complications associated with off-target effects. Herein, as a proof of concept, we introduce an in vivo method using a femtosecond laser to locally optoporate retinal ganglion cells (RGCs) targeted with functionalized gold nanoparticles (AuNPs). We provide evidence that AuNPs functionalized with an antibody toward the cell-surface voltage-gated K+ channel subunit KV1.1 can selectively deliver fluorescently tagged siRNAs or fluorescein isothiocyanate-dextran dye into retinal cells when irradiated with an 800 nm 100 fs laser. Importantly, neither AuNP administration nor irradiation resulted in RGC death. This system provides a novel, non-viral-based approach that has the potential to selectively target retinal cells in diseased regions while sparing healthy areas and may be harnessed in future cell-specific therapies for retinal degenerative diseases.
20 citations
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TL;DR: This review highlights various single-neuron models and their behaviors, followed by different analysis methods, and emphasizes in detail the role of single-NEuron mapping and electrophysiological recording.
Abstract: The brain is an intricate network with complex organizational principles facilitating a concerted communication between single-neurons, distinct neuron populations, and remote brain areas The communication, technically referred to as connectivity, between single-neurons, is the center of many investigations aimed at elucidating pathophysiology, anatomical differences, and structural and functional features In comparison with bulk analysis, single-neuron analysis can provide precise information about neurons or even sub-neuron level electrophysiology, anatomical differences, pathophysiology, structural and functional features, in addition to their communications with other neurons, and can promote essential information to understand the brain and its activity This review highlights various single-neuron models and their behaviors, followed by different analysis methods Again, to elucidate cellular dynamics in terms of electrophysiology at the single-neuron level, we emphasize in detail the role of single-neuron mapping and electrophysiological recording We also elaborate on the recent development of single-neuron isolation, manipulation, and therapeutic progress using advanced micro/nanofluidic devices, as well as microinjection, electroporation, microelectrode array, optical transfection, optogenetic techniques Further, the development in the field of artificial intelligence in relation to single-neurons is highlighted The review concludes with between limitations and future prospects of single-neuron analyses
14 citations
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TL;DR: In this article, a nanosecond pulse laser-assisted photoporation using titanium-oxide nanotubes (TNT) for highly efficient intracellular delivery has been established.
Abstract: In the present study, a newly developed nanosecond pulse laser-assisted photoporation using titanium-oxide nanotubes (TNT) for highly efficient intracellular delivery has been established. The proof of concept for the possibilities of intracellular delivery after irradiation of nanosecond pulse laser on TNT has been validated. TNT on titanium sheets using the electrochemical anodization technique at different voltage and time has been developed. The extensive X-ray photoelectron spectroscopy (XPS) study confirms the presence of different titanium oxide species such as TiO2, TixOy (TiO/Ti2O3/Ti3O5) having different concentrations in TNT formed by different anodization voltage and time along with a minor quantity of Ti metal (Ti0). Formation of sub-oxides results in oxygen defects in TNT. It has also been evidenced from XPS that the anodization voltage and time can change the concentration of oxygen defects on the nanotubes. Due to the formation of oxygen defects, nanotubes have the quasi-metallic and metallic properties. These properties of the nanotubes may facilitate the intracellular delivery by various mechanisms after irradiation of nanosecond pulse laser. Using this technique, we successfully have delivered Propidium iodide (PI) and dextran into HeLa cells (HeLa- human cervical cancer cells) with high transfection efficiency and cell viability on nanotubes formed at 15 V/2 h.
5 citations
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TL;DR: Cells are known to be the most fundamental building block of life and mitochondria are the largest substance in the cell and are thought to be a major component of DNA.
Abstract: Cells are known to be the most fundamental building block of life[...].
4 citations
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TL;DR: Using this platform, a newly developed Titanium oxide micro-flower structure (TMS) for intracellular delivery successfully delivers dyes with 93% efficiency and nearly 98% cell viability into HCT cells, and this technique is potentially applicable for cellular therapy and diagnostics.
Abstract: Introduction of foreign cargo into the targeted living cell with high transfection efficiency and high cell viability is an important mean for many biological and biomedical research purpose. Here, we have demonstrated a newly developed Titanium oxide micro-flower structure (TMS) for intracellular delivery. The TMS were formed on titanium (Ti) substrate using an electrochemical anodization process. The TMS consists of branches of titanium dioxide (TiO2) nanotubes, which play an important role in efficient cargo delivery. Due to nanosecond pulse laser exposure, Ti substrate heat-up, generating cavitation bubbles. These bubbles can rapidly grow, coalesce, and collapse to induce explosion resulting in very strong fluid flow through the TiO2 nanotubes and disrupt the cell plasma membrane promoting the delivery of biomolecules into cells. Using this platform, we successfully deliver dyes with 93% efficiency and nearly 98% cell viability into HCT cells, and this technique is potentially applicable for cellular therapy and diagnostics.
3 citations
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TL;DR: With the development of a leukaemia-like syndrome in two patients cured of a disease by gene therapy, it is timely to contemplate how far this technology has come, and how far it still has to go.
Abstract: Gene therapy has a history of controversy. Encouraging results are starting to emerge from the clinic, but questions are still being asked about the safety of this new molecular medicine. With the development of a leukaemia-like syndrome in two of the small number of patients that have been cured of a disease by gene therapy, it is timely to contemplate how far this technology has come, and how far it still has to go.
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TL;DR: It would be profitable to address a variety of issues and factors that could affect the development of improved targeted drug delivery systems, including nanocarrier, nanovehicle, nanosystem, nanostructure, and other terms used in the literature.
Abstract: The ultimate goal of drug delivery research is to help patients by developing clinically useful formulations. During the last several decades controlled drug delivery technology has advanced significantly, leading to the development of various clinical formulations improving patient compliance and convenience [1]. Current technologies allow delivery of drugs at desired release kinetics for extended periods of time ranging from days to years. Oral and transdermal drug delivery systems routinely deliver drugs for 24 h, substantially improving drug efficacy and minimizing side effects. Implantable systems can locally deliver drugs for months, even years. While significant advances have been made, there are still areas where substantial improvements need to be made to reach the next level of clinical relevance. One such area is targeted drug delivery to solid tumors. The clinically significant impact of targeted drug delivery lies in the ability to specifically target a drug or drug carrier to minimize drug-originated systemic toxic effects.
Successful translation (from bench to bedside) of potential cancer and gene therapies, particularly small interfering RNA (siRNA) delivery, will largely depend on targeted drug delivery strategies. Overcoming the many challenges of identifying a successful targeted drug delivery strategy requires an understanding of events involving transport of drug or drug carrier to a target site after intravenous (i.v.) administration as well as issues relevant for specific target diseases and the body’s response toward a drug delivery system. The current lack of clear recognition of problems facing the drug delivery field can be anticipated to result in only marginal advances in targeted drug delivery technologies in the coming years. The current unmet needs and challenges in this area were summarized by Professor Alexander T. Florence who is one of the few who raised awareness on the exaggerated claims of the nanoparticle-based drug targeting [2,3]. They need to be better appreciated and understood for achieving greater success in drug targeting to tumors. Thus, it would be profitable to address a variety of issues and factors that could affect the development of improved targeted drug delivery systems. Many terms have been used to describe nano-sized drug delivery systems, and here the term “nanoparticle” is used to represent a spectrum of systems, including nanocarrier, nanovehicle, nanosystem, nanostructure, and other terms used in the literature.
1,422 citations
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TL;DR: Further vector refinement and/or development is required before gene therapy will become standard care for any individual disorder, and some clinical successes are over the horizon.
Abstract: Considered by some to be among the simpler forms of life, viruses represent highly evolved natural vectors for the transfer of foreign genetic information into cells. This attribute has led to extensive attempts to engineer recombinant viral vectors for the delivery of therapeutic genes into diseased tissues. While substantial progress has been made, and some clinical successes are over the horizon, further vector refinement and/or development is required before gene therapy will become standard care for any individual disorder.
1,330 citations
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TL;DR: An overview of current applications of ferrofluids (magnetic liquids) in conjunction with magnetic fields as they relate to the latest advances in medical applications and in particular to anticancer treatment is given.
Abstract: Cancer patients often present with localized disease. Yet, surgical eradication or radiation treatment is not always possible or meaningful. Site-directed drug targeting is one way of local or regional antitumor treatment. Magnetically controlled drug targeting is one of the various possibilities of drug targeting. This technology is based on binding established anticancer drugs with ferrofluids that concentrate the drug in the area of interest (tumor site) by means of magnetic fields. Then, the drug desorbs from the ferrofluid and enfolds its mechanism of action. This paper gives the reader an overview of current applications of ferrofluids (magnetic liquids) in conjunction with magnetic fields as they relate to the latest advances in medical applications and in particular to anticancer treatment.
777 citations
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TL;DR: Investigation of mammalian tumor cell migration in confining microenvironments in vitro and in vivo indicates that cell migration incurs substantial physical stress on the NE and its content and requires efficient NE and DNA damage repair for cell survival.
Abstract: During cancer metastasis, tumor cells penetrate tissues through tight interstitial spaces, which requires extensive deformation of the cell and its nucleus. Here, we investigated mammalian tumor cell migration in confining microenvironments in vitro and in vivo. Nuclear deformation caused localized loss of nuclear envelope (NE) integrity, which led to the uncontrolled exchange of nucleo-cytoplasmic content, herniation of chromatin across the NE, and DNA damage. The incidence of NE rupture increased with cell confinement and with depletion of nuclear lamins, NE proteins that structurally support the nucleus. Cells restored NE integrity using components of the endosomal sorting complexes required for transport III (ESCRT III) machinery. Our findings indicate that cell migration incurs substantial physical stress on the NE and its content and requires efficient NE and DNA damage repair for cell survival.
735 citations