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 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 Development of sonosensitive Poly-(L)-lactic acid nanoparticles

2017 ◽  
Vol 3 (2) ◽  
pp. 679-682 ◽  
Author(s):  
Pia-Theresa Hiltl ◽  
Michael Fink ◽  
Stefan J. Rupitsch ◽  
Geoffrey Lee ◽  
Helmut Ermert
Keyword(s):  
Drug Delivery ◽  
Lactic Acid ◽  
Acoustic Pressure ◽  
Region Of Interest ◽  
Ultrasound Wave ◽  
Chemotherapeutic Drugs ◽  
Epr Effect ◽  
Inertial Cavitation ◽  
Treatment Techniques ◽  
Freeze Dried

AbstractDue to serious side effects of traditional chemotherapeutic treatment, novel treatment techniques like targeted drug delivery, which allows a reduction of the overall dosage of drugs, are investigated. It is worth mentioning that at the same time, precise drug delivery offers an increased dosage of chemotherapeutic drugs in the tumorous area employing the EPR effect. Therefore, vehicles smaller than 400 nm can be used to pass the poorly aligned endothelial cells of tumour vessels passively through their fenestrations. In a subsequent step, the chemotherapeutic drugs need to be released. One possibility is an ultrasound-based release via inertial cavitation. Thereby, it is desirable to restrict the drug release to a narrow range. Thus, the cavitation inducing ultrasound wave has to be focused to that region of interest. Ultrasound frequencies of more than 500 kHz enable sufficient focusing, however, inertial cavitation occurs primarily at much lower frequencies. In order to afford inertial cavitation at 500 kHz, either bigger particles in the range of micrometres are needed as cavitation nucleus, which is not possible due to the EPR effect or high acoustic pressure is needed to generate inertial cavitation. Nevertheless, this high pressure is inappropriate for clinical applications due to thermal and mechanical effects on biological tissue.We have produced Poly-(L)-lactic acid (PLLA) nanoparticles by a solvent evaporation technique that serve as nucleus for inertial cavitation at moderate acoustic pressure of 800 kPa and at high frequencies of 800 kHz after the particles have been freeze-dried. In this contribution, we characterize the designed particles and present the production process. Moreover, we show that these particles enable inertial cavitation at an acoustic pressure and at acoustic frequencies which are commonly used in clinical ultrasound units. We also show that other particles with the same size at the same acoustic parameters do not induce cavitation activity.

scholarly journals Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood–brain barrier opening

2016 ◽  
Vol 37 (4) ◽  
pp. 1236-1250 ◽  
Author(s):  
Carlos Sierra ◽  
Camilo Acosta ◽  
Cherry Chen ◽  
Shih-Ying Wu ◽  
Maria E Karakatsani ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Targeted Drug Delivery ◽  
Focused Ultrasound ◽  
Brain Barrier ◽  
Inertial Cavitation ◽  
Blood Brain ◽  
Targeted Drug ◽  
Cavitation Detection

Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood–brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood–brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo.

The Improvement of Paclitaxel Cytotoxicity using Nanocellulose based Nature Resources

2019 ◽  
Vol 1 (1) ◽  
pp. 7
Author(s):  
R Nahrowi ◽  
A Setiawan ◽  
Noviany Noviany ◽  
I Sukmana ◽  
S D Yuwono
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Natural Resources ◽  
Cell Viability ◽  
Cancer Cells ◽  
Drug Delivery System ◽  
Target Cell ◽  
Mitotic Cycle ◽  
Potential Sources ◽  
Local Accumulation

Paclitaxel is one of the cancer drugs that often used. These drug kills cancer cells byinhibiting mitotic cycle. The efficiency of paclitaxel is increased by the use ofnanomaterials as a carrier of paclitaxel. Nanomaterials can enhance encapsulationefficiency, improve the drug release to the target cell following nanomaterialdegradation, and improve local accumulation of drug in the cell through endocytosisreceptor. Nanomaterial that often used forencapsulation of paclitaxel is a polymerderived from natural resources such as cellulose. The advantages of cellulose as acarrier of paclitaxel are nontoxic, biodegradable, and very abundant from varioussources. One of the potential sources of cellulose for drug delivery system is cassavabaggase.Keywords: Paclitaxel, encapsulation, cell viability, nanocellulose

Acyclovir Loaded Solid Lipid Nanoparticle Based Cream: A Novel Drug Delivery System

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
EL- Assal I. A. ◽  
Retnowati .
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Antiviral Agent ◽  
Study Drug ◽  
Particle Size Analysis ◽  
Stability Study ◽  
Size Analysis ◽  
Solid Lipid ◽  
Dermal Delivery

Objective of the present investigation was enthused by the possibility to develop solid lipid nanoparticles (SLNs) of hydrophilic drug acyclovir. Also study vitro and vivo drug delivery. Methods: Drug loaded SLNs (ACV-SLNs) were prepared by high pressure homogenization of aqueous surfactant solutions containing the drug-loaded lipids in the melted or in the solid state with formula optimization study (Different lipid concentration, drug loaded, homogenization / stirring speed and compritol 888ATO: drug ratio). ACV - SLN incorporated in cream base. The pH was evaluated and rheological study. Drug release was evaluated and compared with simple cream- drug, ACV – SLN with compritol 888ATO and marketed cream. The potential of SLN as the carrier for dermal delivery was studied. Results: Particle size analysis of SLNs prove small, smooth, spherical shape particle ranged from 150 to 200 nm for unloaded and from 330 to 444 nm for ACV loaded particles. The EE% for optimal formula is 72% with suitable pH for skin application. Rheological behavior is shear thinning and thixotropic. Release study proved controlled drug release for SLNs especially in formula containing compritol88 ATO. Stability study emphasized an insignificant change in SLNs properties over 6 month. In-vivo study showed significantly higher accumulation of ACV in stratum corneum, dermal layer, and receptor compartment compared with blank skin. Conclusion: AVC-loaded SLNs might be beneficial in controlling drug release, stable and improving dermal delivery of antiviral agent(s).

Development and Evaluation of Floating Pulsatile Drug Delivery System Using Meloxicam

2017 ◽  
Vol 7 (04) ◽  
Author(s):  
ShirishaG. Suddala ◽  
S. K. Sahoo ◽  
M. R. Yamsani
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Delivery ◽  
Drug Release ◽  
Drug Delivery System ◽  
Delivery System ◽  
Lag Time ◽  
Oral Dosage ◽  
Lag Phase ◽  
Pulsatile Drug Delivery

Objective: The objective of this research work was to develop and evaluate the floating– pulsatile drug delivery system (FPDDS) of meloxicam intended for Chrono pharmacotherapy of rheumatoid arthritis. Methods: The system consisting of drug containing core, coated with hydrophilic erodible polymer, which is responsible for a lag phase for pulsatile release, top cover buoyant layer was prepared with HPMC K4M and sodium bicarbonate, provides buoyancy to increase retention of the oral dosage form in the stomach. Meloxicam is a COX-2 inhibitor used to treat joint diseases such as osteoarthritis and rheumatoid arthritis. For rheumatoid arthritis Chrono pharmacotherapy has been recommended to ensure that the highest blood levels of the drug coincide with peak pain and stiffness. Result and discussion: The prepared tablets were characterized and found to exhibit satisfactory physico-chemical characteristics. Hence, the main objective of present work is to formulate FPDDS of meloxicam in order to achieve drug release after pre-determined lag phase. Developed formulations were evaluated for in vitro drug release studies, water uptake and erosion studies, floating behaviour and in vivo radiology studies. Results showed that a certain lag time before drug release which was due to the erosion of the hydrophilic erodible polymer. The lag time clearly depends on the type and amount of hydrophilic polymer which was applied on the inner cores. Floating time and floating lag time was controlled by quantity and composition of buoyant layer. In vivo radiology studies point out the capability of the system of longer residence time of the tablets in the gastric region and releasing the drug after a programmed lag time. Conclusion: The optimized formulation of the developed system provided a lag phase while showing the gastroretension followed by pulsatile drug release that would be beneficial for chronotherapy of rheumatoid arthritis and osteoarthritis.

Formulation, Development and Characterization of Floating Beads of Diltiazem Hydrochloride

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Anamika Saxena Saxena ◽  
Santosh Kitawat ◽  
Kalpesh Gaur ◽  
Virendra Singh
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Drug Delivery Systems ◽  
Entrapment Efficiency ◽  
Repeated Administration ◽  
Alginate Beads ◽  
Delivery Systems ◽  
Sem Analysis ◽  
Formulation Development

The main goal of any drug delivery system is to achieve desired concentration of the drug in blood or tissue, which is therapeutically effective and nontoxic for a prolonged period. Various attempts have been made to develop gastroretentive delivery systems such as high density system, swelling, floating system. The recent developments of FDDS including the physiological and formulation variables affecting gastric retention, approaches to design single-unit and multiple-unit floating systems, and their classification and formulation aspects are covered in detail. Gastric emptying is a complex process and makes in vivo performance of the drug delivery systems uncertain. In order to avoid this variability, efforts have been made to increase the retention time of the drug-delivery systems for more than 12 hours. The floating or hydrodynamically controlled drug delivery systems are useful in such application. Background of the research: Diltiazem HCL (DTZ), has short biological half life of 3-4 h, requires rather high frequency of administration. Due to repeated administration there may be chances of patient incompliance and toxicity problems. Objective: The objective of study was to develop sustained release alginate beads of DTZ for reduction in dosing frequency, high bioavailability and better patient compliance. Methodology: Five formulations prepared by using different drug to polymer ratios, were evaluated for relevant parameters and compared. Alginate beads were prepared by ionotropic external gelation technique using CaCl2 as cross linking agent. Prepared beads were evaluated for % yield, entrapment efficiency, swelling index in 0.1N HCL, drug release study and SEM analysis. In order to improve %EE and drug release, LMP and sunflower oil were used as copolymers along with sodium alginate.

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