Applications of Ultrasound-Mediated Drug Delivery and Gene Therapy.
Ontology highlight
ABSTRACT:
SUBMITTER: Sitta J
PROVIDER: S-EPMC8583720 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:There is a significant clinical need for rapid and efficient delivery of drugs directly to the site of diseased tissues for the treatment of gastrointestinal (GI) pathologies, in particular, Crohn's and ulcerative colitis. However, complex therapeutic molecules cannot easily be delivered through the GI tract because of physiologic and structural barriers. We report the use of ultrasound as a modality for enhanced drug delivery to the GI tract, with an emphasis on rectal delivery. Ultrasound increased the absorption of model therapeutics inulin, hydrocortisone, and mesalamine two- to tenfold in ex vivo tissue, depending on location in the GI tract. In pigs, ultrasound induced transient cavitation with negligible heating, leading to an order of magnitude enhancement in the delivery of mesalamine, as well as successful systemic delivery of a macromolecule, insulin, with the expected hypoglycemic response. In a rodent model of chemically induced acute colitis, the addition of ultrasound to a daily mesalamine enema (compared to enema alone) resulted in superior clinical and histological scores of disease activity. In both animal models, ultrasound treatment was well tolerated and resulted in minimal tissue disruption, and in mice, there was no significant effect on histology, fecal score, or tissue inflammatory cytokine levels. The use of ultrasound to enhance GI drug delivery is safe in animals and could augment the efficacy of GI therapies and broaden the scope of agents that could be delivered locally and systemically through the GI tract for chronic conditions such as inflammatory bowel disease.
| S-EPMC4825174 | biostudies-literature
Project description:Gene therapy is a powerful tool against genetic disorders and cancer, targeting the source of the disease rather than just treating the symptoms. While much of the initial success of gene delivery relied on viral vectors, non-viral vectors are emerging as promising gene delivery systems for efficacious treatment with decreased toxicity concerns. However, the delivery of genetic material is still challenging, and there is a need for vectors with enhanced targeting, reduced toxicity, and controlled release. In this article, we highlight current work in gene therapy which utilizes the cyclic oligosaccharide molecule cyclodextrin (CD). With a number of unique abilities, such as hosting small molecule drugs, acting as a linker or modular component, reducing immunogenicity, and disrupting membranes, CD is a valuable constituent in many delivery systems. These carriers also demonstrate great promise in combination therapies, due to the ease of assembling macromolecular structures and wide variety of chemical derivatives, which allow for customizable delivery systems and co-delivery of therapeutics. The use of combination and personalized therapies can result in improved patient health-modular systems, such as those which incorporate CD, are more conducive to these therapy types. Graphical abstract.
| S-EPMC7524011 | biostudies-literature
Project description:Theranostic agents present a promising clinical approach for cancer detection and treatment. We herein introduce a microbubble and liposome complex (MB-Lipo) developed for ultrasound (US) imaging and activation. The MB-Lipo particles have a hybrid structure consisting of a MB complexed with multiple Lipos. The MB components are used to generate high echo signals in US imaging, while the Lipos serve as a versatile carrier of therapeutic materials. MB-Lipo allows high contrast US imaging of tumor sites. More importantly, the application of high acoustic pressure bursts MBs, which releases therapeutic Lipos and further enhances their intracellular delivery through sonoporation effect. Both imaging and drug release could thus be achieved by a single US modality, enabling in situ treatment guided by real-time imaging. The MB-Lipo system was applied to specifically deliver anti-cancer drug and genes to tumor cells, which showed enhanced therapeutic effect. We also demonstrate the clinical potential of MB-Lipo by imaging and treating tumor in vivo.
| S-EPMC4165777 | biostudies-literature
Project description:Genetic diseases seriously threaten human health and have always been one of the refractory conditions facing humanity. Currently, gene therapy drugs such as siRNA, shRNA, antisense oligonucleotide, CRISPR/Cas9 system, plasmid DNA and miRNA have shown great potential in biomedical applications. To avoid the degradation of gene therapy drugs in the body and effectively deliver them to target tissues, cells and organelles, the development of excellent drug delivery vehicles is of utmost importance. Viral vectors are the most widely used delivery vehicles for gene therapy in vivo and in vitro due to their high transfection efficiency and stable transgene expression. With the development of nanotechnology, novel nanocarriers are gradually replacing viral vectors, emerging superior performance. This review mainly illuminates the current widely used gene therapy drugs, summarizes the viral vectors and non-viral vectors that deliver gene therapy drugs, and sums up the application of gene therapy to treat genetic diseases. Additionally, the challenges and opportunities of the field are discussed from the perspective of developing an effective nano-delivery system.
| S-EPMC8737406 | biostudies-literature
Project description:Therapeutic ultrasound strategies that harness the mechanical activity of cavitation nuclei for beneficial tissue bio-effects are actively under development. The mechanical oscillations of circulating microbubbles, the most widely investigated cavitation nuclei, which may also encapsulate or shield a therapeutic agent in the bloodstream, trigger and promote localized uptake. Oscillating microbubbles can create stresses either on nearby tissue or in surrounding fluid to enhance drug penetration and efficacy in the brain, spinal cord, vasculature, immune system, biofilm or tumors. This review summarizes recent investigations that have elucidated interactions of ultrasound and cavitation nuclei with cells, the treatment of tumors, immunotherapy, the blood-brain and blood-spinal cord barriers, sonothrombolysis, cardiovascular drug delivery and sonobactericide. In particular, an overview of salient ultrasound features, drug delivery vehicles, therapeutic transport routes and pre-clinical and clinical studies is provided. Successful implementation of ultrasound and cavitation nuclei-mediated drug delivery has the potential to change the way drugs are administered systemically, resulting in more effective therapeutics and less-invasive treatments.
| S-EPMC7189181 | biostudies-literature
Project description:Lignin is an abundant renewable natural biopolymer. Moreover, a significant development in lignin pretreatment and processing technologies has opened a new window to explore lignin and lignin-based bionanomaterials. In the last decade, lignin has been widely explored in different applications such as drug and gene delivery, tissue engineering, food science, water purification, biofuels, environmental, pharmaceuticals, nutraceutical, catalysis, and other interesting low-value-added energy applications. The complex nature and antioxidant, antimicrobial, and biocompatibility of lignin attracted its use in various biomedical applications because of ease of functionalization, availability of diverse functional sites, tunable physicochemical and mechanical properties. In addition to it, its diverse properties such as reactivity towards oxygen radical, metal chelation, renewable nature, biodegradability, favorable interaction with cells, nature to mimic the extracellular environment, and ease of nanoparticles preparation make it a very interesting material for biomedical use. Tremendous progress has been made in drug delivery and tissue engineering in recent years. However, still, it remains challenging to identify an ideal and compatible nanomaterial for biomedical applications. In this review, recent progress of lignin towards biomedical applications especially in drug delivery and in tissue engineering along with challenges, future possibilities have been comprehensively reviewed.
| S-EPMC8009556 | biostudies-literature
Project description:One of the major obstacles to successful chemotherapy is multi-drug resistance (MDR). A multi-drug resistant cancerous cell abnormally overexpresses membrane transporters that pump anticancer drugs out of the cell, resulting in low anticancer drug delivery efficiency. To overcome the limitation, many attempts have been performed to inhibit the abilities of efflux receptors chemically or genetically or to increase the delivery efficiency of anticancer drugs. However, the results have not yet been satisfactory. In this study, we developed nanoparticle-microbubble complexes (DOX-NPs/Ce6-MBs) by conjugating doxorubicin loaded human serum albumin nanoparticles (DOX-NPs) onto the surface of Chlorin e6 encapsulated microbubbles (Ce6-MBs) in order to maximize anticancer efficiency by overcoming MDR. Under the ultrasound irradiation, DOX-NPs and Ce6 encapsulating self-assembled liposomes or micelles were effectively delivered into the cells due to the sonoporation effect caused by the microbubble cavitation. At the same time, reactive oxygen (ROS) generated from intracellularly delivered Ce6 by laser irradiation arrested the activity of ABCG2 efflux receptor overexpressed in doxorubicin-resistant breast cancer cells (MCF-7/ADR), resulting in increased the chemotherapy efficacy. In addition, the total number of side population cells that exhibit the properties of cancer stem-like cells were also reduced by the combination of photodynamic therapy and chemotherapy. In conclusion, DOX-NPs/Ce6-MBs will provide a platform for simultaneously overcoming MDR and increasing drug delivery and therefore, treatment efficiency, under ultrasound irradiation.
| S-EPMC7479087 | biostudies-literature
Project description:Chemotherapy efficacy is often reduced by insufficient drug uptake in tumor cells. The combination of ultrasound and microbubbles (USMB) has been shown to improve drug delivery and to enhance the efficacy of several drugs in vitro and in vivo, through effects collectively known as sonopermeation. However, clinical translation of USMB therapy is hampered by the large variety of (non-clinical) US set-ups and US parameters that are used in these studies, which are not easily translated to clinical practice. In order to facilitate clinical translation, the aim of this study was to prove that USMB therapy using a clinical ultrasound system (Philips iU22) in combination with clinically approved microbubbles (SonoVue) leads to efficient in vitro sonopermeation. To this end, we measured the efficacy of USMB therapy for different US probes (S5-1, C5-1 and C9-4) and US parameters in FaDu cells. The US probe with the lowest central frequency (i.e. 1.6 MHz for S5-1) showed the highest USMB-induced intracellular uptake of the fluorescent dye SYTOX™ Green (SG). These SG uptake levels were comparable to or even higher than those obtained with a custom-built US system with optimized US parameters. Moreover, USMB therapy with both the clinical and the custom-built US system increased the cytotoxicity of the hydrophilic drug bleomycin. Our results demonstrate that a clinical US system can be used to perform USMB therapy as efficiently as a single-element transducer set-up with optimized US parameters. Therefore, future trials could be based on these clinical US systems, including validated US parameters, in order to accelerate successful translation of USMB therapy.
| S-EPMC8560689 | biostudies-literature
Project description:Novel effective therapeutic strategies are needed to treat brain neurodegenerative diseases and to improve the quality of life of patients affected by Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic Lateral sclerosis (ALS) as well as other brain conditions. At present no effective treatment options are available; current therapeutics for neurodegenerative diseases (NDs) improve cognitive symptoms only transiently and in a minor number of patients. Further, most of the amyloid-based phase III clinical trials recently failed in AD, in spite of promising preclinical and phase I-II clinical trials, further pinpointing the need for a better knowledge of the early mechanisms of disease as well as of more effective routes of drug administration. In fact, beyond common pathological events and molecular substrates, each of these diseases preferentially affect defined subpopulations of neurons in specific neuronal circuits (selective neuronal vulnerability), leading to the typical age-related clinical profile. In this perspective, key to successful drug discovery is a robust and reproducible biological validation of potential new molecular targets together with a concomitant set up of protocols/tools for efficient and targeted brain delivery to a specific area of interest. Here we propose and discuss Focused UltraSound aided drug administration as a specific and novel technical approach to achieve optimal concentration of the drug at the target area of interest. We will focus on drug delivery to the brain through the nasal route coupled to FUS as a promising approach to achieve neuroprotection and rescue of cognitive decline in several NDs.
| S-EPMC9046653 | biostudies-literature
Project description:Acoustic Cluster Therapy (ACT) represents a novel concept for targeted drug delivery. Ultrasound is applied to activate intravenously administered free-flowing clusters of microbubbles and microdroplets within the target pathology, depositing 20-30 ?m large bubbles in the microvasculature for 5-10 min. Further application of ultrasound induces biomechanical effects which increase vascular permeability and enhance localized extravasation of coadministered drugs. Herein we report investigations done to assess the preclinical safety of ACT, using doses up to 1 mL/kg (3 ?L perfluoromethyl-cyclopentane/kg). In dogs, half the animals were exposed to ultrasound activation in the heart for 1 min, no ultrasound was applied in the other half. Posttreatment observation time was 24 h. Clinical signs, ophthalmoscopy, clinical pathology, macro-, and microscopy were used as endpoints. No differences between groups with and without ultrasound activation were observed. Short-lasting leukopenia and thrombocytopenia, possibly secondary to a slight and short-lasting increase in plasma histamine and complement split products, were the only effects noted. In rats ACT was activated in the liver for 5 min. Histopathology and clinical chemistry parameters remained unchanged. Lastly, rats were treated with ACT activated in the heart and thereafter placed on a rotarod for evaluation of motor coordination. No differences were observed between animals treated with ACT and controls. In conclusion, ACT appeared safe at dose-levels up to 1 mL/kg and with activation either in the heart or the liver. These results, together with positive efficacy data upon coinjection with cytotoxic compounds encourage further preclinical safety studies with the objective of entering subsequent clinical trials.
| S-EPMC5226284 | biostudies-other