scholarly journals Investigation of Inertial Cavitation of Sonosensitive and Biocompatible Nanoparticles in Flow - Through Tissue- Mimicking Phantoms Employing Focused Ultrasound

2021 ◽  
Vol 7 (2) ◽  
pp. 163-166
Author(s):  
Benedikt George ◽  
Ula Savšek ◽  
Dagmar Fischer ◽  
Helmut Ermert ◽  
Stefan J. Rupitsch
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Drug Release ◽  
Focused Ultrasound ◽  
Vascular System ◽  
Drug Carriers ◽  
Inertial Cavitation ◽  
Cavitation Effect ◽  
Flow Through ◽  
Delivery Approach

Abstract A promising approach to drug delivery applications for chemotherapeutics is the use of drug carriers to reduce the total amount of cytostatics, minimizing side effects. In addition, the carriers, loaded with the drug, can be guided to the tumorous tissue via the vascular system, which enables a local drug release (LDR). In our case, LDR is activated due to the sonosensitive behavior of the nanocapsules by inertial cavitation (IC) caused by focused ultrasound (FUS). Thereby, IC is excited by employing sound pressures within the recommended limit allowed for diagnostic ultrasound. In order to verify this drug delivery approach for its clinical suitability, a tissue-mimicking flow -through phantom, containing a small vessel, is used. Investigations have shown that the drug releasing cavitation effect associated with the sonosensitive and biocompatible nanocapsules also occurs in fine vessel structures, even in the case of moving particles and vessel diameters dc smaller than the wavelength λ.

scholarly journals Investigation of the Inertial Cavitation Activity of Sonosensitive and Biocompatible Nanoparticles for Drug Delivery Applications Employing High Intensity Focused Ultrasound

2019 ◽  
Vol 5 (1) ◽  
pp. 585-588
Author(s):  
Benedikt George ◽  
Michael Fink ◽  
Helmut Ermert ◽  
Stefan J. Rupitsch ◽  
Pia T. Hiltl ◽  
...  
Keyword(s):  
Drug Release ◽  
High Intensity ◽  
Focused Ultrasound ◽  
Active Drug ◽  
Drug Carriers ◽  
High Intensity Focused Ultrasound ◽  
Activity Level ◽  
Inertial Cavitation ◽  
Cavitation Effect ◽  
Cavitation Activity

AbstractAn approach to improve chemotherapy, while minimizing side effects, is a local drug release close to the tumorous tissue. For this purpose, the active drug component is often bound to nanoparticles employed as drug carriers. In the present study, we investigate sonosensitive, biocompatible poly-(L)-lactic acid (PLA) nanoparticles, which shall be used as drug carriers. For drug release, High Intensity Focused Ultrasound (HIFU) will be employed to introduce inertial cavitation, which separates the active drug component from the drug carrier. The cavitation effect generates an acoustic noise signal, which characterizes the cavitation activity and is expected to serve simultaneously as an indicator for the release of the active drug component. Depending on the ultrasound frequency, different acoustic levels of the inertial cavitation activity were measured. Investigations using a setup for passive cavitation detection (PCD) deliver quantitative results regarding the frequency dependence of the cavitation activity level of nanoparticles and reference media.

scholarly journals Determination of the Cavitation Pressure Threshold in Focused Ultrasound Wave Fields applied to Sonosensitive, Biocompatible Nanoparticles for Drug Delivery Applications

2020 ◽  
Vol 6 (3) ◽  
pp. 539-542
Author(s):  
Benedikt George ◽  
Markus Lehner ◽  
Michael Fink ◽  
Stefan J. Rupitsch ◽  
Helmut Ermert ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Focused Ultrasound ◽  
Ultrasound Wave ◽  
Pharmaceutical Ingredients ◽  
Inertial Cavitation ◽  
Biocompatible Nanoparticles ◽  
Pressure Threshold ◽  
Cavitation Pressure

AbstractEmploying sonosensitive nanoparticles as carriers of active pharmaceutical ingredients emerges in ultrasonic Drug Delivery. Drug release can be initiated by focused ultrasound via the effect of inertial cavitation in certain target areas of particle loaded tissue. For stimulating inertial cavitation, a specific peak rarefaction pressure threshold must be exceeded. This pressure threshold has to be determined in order to estimate the risk of tissue damage during the drug release procedure. Therefore, this study provides a method to reliably verify the cavitation pressure threshold of sonosensitive and biocompatible nanoparticles.

scholarly journals Blood-brain barrier opening with focused ultrasound in Parkinson’s disease dementia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carmen Gasca-Salas ◽  
Beatriz Fernández-Rodríguez ◽  
José A. Pineda-Pardo ◽  
Rafael Rodríguez-Rojas ◽  
Ignacio Obeso ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Neurodegenerative Disorders ◽  
Focused Ultrasound ◽  
Temporal Cortex ◽  
Clinical State ◽  
Cognitive Improvement ◽  
Bbb Opening

AbstractMR-guided focused ultrasound (MRgFUS), in combination with intravenous microbubble administration, has been applied for focal temporary BBB opening in patients with neurodegenerative disorders and brain tumors. MRgFUS could become a therapeutic tool for drug delivery of putative neurorestorative therapies. Treatment for Parkinson’s disease with dementia (PDD) is an important unmet need. We initiated a prospective, single-arm, non-randomized, proof-of-concept, safety and feasibility phase I clinical trial (NCT03608553), which is still in progress. The primary outcomes of the study were to demonstrate the safety, feasibility and reversibility of BBB disruption in PDD, targeting the right parieto-occipito-temporal cortex where cortical pathology is foremost in this clinical state. Changes in β-amyloid burden, brain metabolism after treatments and neuropsychological assessments, were analyzed as exploratory measurements. Five patients were recruited from October 2018 until May 2019, and received two treatment sessions separated by 2–3 weeks. The results are set out in a descriptive manner. Overall, this procedure was feasible and reversible with no serious clinical or radiological side effects. We report BBB opening in the parieto-occipito-temporal junction in 8/10 treatments in 5 patients as demonstrated by gadolinium enhancement. In all cases the procedures were uneventful and no side effects were encountered associated with BBB opening. From pre- to post-treatment, mild cognitive improvement was observed, and no major changes were detected in amyloid or fluorodeoxyglucose PET. MRgFUS-BBB opening in PDD is thus safe, reversible, and can be performed repeatedly. This study provides encouragement for the concept of BBB opening for drug delivery to treat dementia in PD and other neurodegenerative disorders.

scholarly journals Targeted Drug Delivery Systems for the Treatment of Glaucoma: Most Advanced Systems Review

Polymers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1742 ◽  
Author(s):  
Olga Cegielska ◽  
Paweł Sajkiewicz
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Targeted Delivery ◽  
Drug Targets ◽  
Drug Delivery Systems ◽  
Release Kinetics ◽  
Controlled Drug Release ◽  
Drug Carriers ◽  
Delivery Systems ◽  
Drug Bioavailability

Each year, new glaucoma drug delivery systems are developed. Due to the chronic nature of the disease, it requires the inconvenient daily administration of medications. As a result of their elution from the eye surface and penetration to the bloodstream through undesired permeation routes, the bioavailability of active compounds is low, and systemic side effects occur. Despite numerous publications on glaucoma drug carriers of controlled drug release kinetics, only part of them consider drug permeation routes and, thus, carriers’ location, as an important factor affecting drug delivery. In this paper, we try to demonstrate the importance of the delivery proximal to glaucoma drug targets. The targeted delivery can significantly improve drug bioavailability, reduce side effects, and increase patients’ compliance compared to both commercial and scientifically developed formulations that can spread over the eye surface or stay in contact with conjunctival sac. We present a selection of glaucoma drug carriers intended to be placed on cornea or injected into the aqueous humor and that have been made by advanced materials using hi-tech forming methods, allowing for effective and convenient sustained antiglaucoma drug delivery.

scholarly journals Investigation of an Active Measurement Method to Detect Inertial Cavitation and the Presence of Potential Drug Carriers

2021 ◽  
Vol 7 (2) ◽  
pp. 883-886
Author(s):  
Jan Helmerich ◽  
Benedikt George ◽  
Stefan J. Rupitsch
Keyword(s):  
Measurement Method ◽  
Closed Loop ◽  
Focused Ultrasound ◽  
Drug Carriers ◽  
Closed Loop Control ◽  
Potential Drug ◽  
Loop Control ◽  
Passive Measurement ◽  
Inertial Cavitation ◽  
Active Measurement

Abstract Drug carriers, such as nanoparticles, are capable of releasing pharmaceutically active ingredients, which can be initiated by focused ultrasound via the effect of inertial cavitation. This effect of inertial cavitation is often verified by passive measurement methods that rely on the analysis of emitted acoustic signals caused by the implosion of bubbles. However, a major issue of such methods is their inability to detect the presence of potential drugs in human vessels, complicating the implementation of a closed loop control for future medical therapies. Therefore, this contribution introduces an active measurement method to determine both inertial cavitation and the presence of potential drug carriers in a tissue mimicking phantom

Tyrosinase-responsive tumor-specific cascade amplification drug release system for melanoma therapy

2021 ◽  
Author(s):  
Dongdong Li ◽  
Xiaoxuan Zhou ◽  
Wei Zhang ◽  
Hongxia Xu ◽  
Bing Xiao ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Drug Release ◽  
Tumor Heterogeneity ◽  
Drug Delivery Systems ◽  
Drug Side Effects ◽  
Anticancer Efficacy ◽  
Cascade Amplification ◽  
Tumor Selective ◽  
Melanoma Therapy

Tumor-selective drug delivery could enhance anticancer efficacy and avoid drug side effects. However, because of tumor heterogeneity, current nanoparticle-based drug delivery systems rarely improve clinical outcomes significantly, commonly only reducing...

scholarly journals High Intensity Focused Ultrasound Technology, its Scope and Applications in Therapy and Drug Delivery

2014 ◽  
Vol 17 (1) ◽  
pp. 136 ◽  
Author(s):  
Christopher Peter Phenix ◽  
Melissa Togtema ◽  
Samuel Pichardo ◽  
Ingeborg Zehbe ◽  
Laura Curiel
Keyword(s):  
Drug Delivery ◽  
High Intensity ◽  
Focused Ultrasound ◽  
Biological Effects ◽  
Pharmaceutical Research ◽  
Drug Carriers ◽  
High Intensity Focused Ultrasound ◽  
Temperature Sensitive ◽  
Therapeutic Applications ◽  
Living Tissues

Ultrasonography is a safe, inexpensive and wide-spread diagnostic tool capable of producing real-time non-invasive images without significant biological effects. However, the propagation of higher energy, intensity and frequency ultrasound waves through living tissues can induce thermal, mechanical and chemical effects useful for a variety of therapeutic applications. With the recent development of clinically approved High Intensity Focused Ultrasound (HIFU) systems, therapeutic ultrasound is now a medical reality.  Indeed, HIFU has been used for the thermal ablation of pathological lesions; localized, minimally invasive ultrasound-mediated drug delivery through the transient formation of pores on cell membranes; the temporary disruption of skin and the blood brain barrier; the ultrasound induced break-down of blood clots; and the targeted release of drugs using ultrasound and temperature sensitive drug carriers. This review seeks to engage the pharmaceutical research community by providing an overview on the biological effects of ultrasound as well as highlighting important therapeutic applications, current deficiencies and future directions.This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Control of Cancer Growth Using Two Input Autonomous Fuzzy Nanoparticles

NANO ◽  
2015 ◽  
Vol 10 (04) ◽  
pp. 1550062 ◽  
Author(s):  
Fahimeh Razmi ◽  
Reihaneh Kardehi Moghaddam ◽  
Alireza Rowhanimanesh
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Simple Structure ◽  
Medication Use ◽  
Drug Carriers ◽  
Local Drug Delivery ◽  
Cancer Growth ◽  
Simulation Results

A major challenge in cancer therapy is destroying cancer cells with least side effects on healthy cells. In this paper, autonomous drug-encapsulated nanoparticle (ADENP) with a real feedback control is recommended to prevent from the growth of cancerous tumors and treatment of them. The proposed ADENPs, swarmly perform local drug delivery which leads to significant reduction in side effects on healthy tissues in comparison to global drug delivery. The proposed ADENPs every moment, take feedback directly from drugs and cancer cells and at any time decide how much drugs to release. Also, these ADENPs have the capability of distinguishing unhealthy from healthy tissues, and medication use of these nanoparticles is more efficient than drug carriers. Another feature of these ADENPs is their simple structure in comparison to nanorobots. Simulation results show that ADENPs successfully reduce the number of cancer cells with minimal side effects.

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