scholarly journals Combination Therapy with Doxorubicin-Loaded Reduced Albumin Nanoparticles and Focused Ultrasound in Mouse Breast Cancer Xenografts

2020 ◽  
Vol 13 (9) ◽  
pp. 235
Author(s):  
Daehyun Kim ◽  
Seung Soo Lee ◽  
Woo Young Yoo ◽  
Hyungwon Moon ◽  
Aesin Cho ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Half Life ◽  
Focused Ultrasound ◽  
Tumor Response ◽  
Precise Control ◽  
Albumin Nanoparticles ◽  
Enhanced Permeability And Retention ◽  
Modern Drug ◽  
Mouse Breast Cancer ◽  
Breast Cancer Xenografts

Because chemotherapeutic drugs are often associated with serious side effects, the central topic in modern drug delivery is maximizing the localization of drugs at the target while minimizing non-specific drug interactions at unwanted regions. To address this issue, biocompatible nanoparticles have been developed to enhance the drug half-life while minimizing the associated toxicity. Nevertheless, relying solely on the enhanced half-life and enhanced permeability and retention (EPR) effects has been ineffective, and designing stimulus-sensitive nanoparticles to introduce the precise control of drug release has been desired. In this paper, we introduce a pH-sensitive, reduced albumin nanoparticle in combination with focused ultrasound treatment. Not only did these nanoparticles have superior therapeutic efficacy and toxicity profiles when compared to the free drugs in xenograft mouse models, but we were also able to show that the albumin nanoparticles reported in this paper were more suitable than other types of non-reduced albumin nanoparticles as vehicles for drug delivery. As such, we believe that the albumin nanoparticles presented in this paper with desirable characteristics including the induction of strong anti-tumor response, precise control, and superior safety profiles hold strong potential for preclinical and clinical anticancer therapy.

scholarly journals Antitumor Efficacy of Focused Ultrasound-MFL Nanoparticles Combination Therapy in Mouse Breast Cancer Xenografts

Materials ◽  
2020 ◽  
Vol 13 (5) ◽  
pp. 1099
Author(s):  
Daehyun Kim ◽  
Junhee Han ◽  
So Yeon Park ◽  
Heegon Kim ◽  
Ji-Ho Park ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Focused Ultrasound ◽  
Delivery Method ◽  
Drug Delivery Vehicles ◽  
Drug Loss ◽  
Mouse Breast Cancer ◽  
Delivery Vehicles ◽  
High Doses ◽  
Chemotherapy Agents ◽  
Breast Cancer Xenografts

High doses of chemotherapy agents can cause adverse effects. To address this issue, drug-loaded vesicles with minimum drug loss, guided by an external element for precise delivery, are desired. Combinational therapy of both a focused ultrasound-induced drug delivery method and membrane fusogenic liposomes (MFLs) as drug delivery vehicles can satisfy such premises. In this study, we confirmed that the use of a small quantity of docetaxel-loaded membrane fusogenic liposomes (DTX-MFL) with focused ultrasound can induce better antitumor response in a xenograft mouse model compared to conventional docetaxel monotherapy and DTX-MFL only.

Plantago Ovata and Locust Bean Gum as a Natural Polymer in Hydrodynamically Balanced Systems: A Review

2020 ◽  
Author(s):  
Ghildiyal s
Keyword(s):  
Drug Delivery ◽  
Locust Bean Gum ◽  
Main Role ◽  
Natural Polymer ◽  
Release Formulation ◽  
Sustained Drug Delivery ◽  
Modern Drug ◽  
Buccal Drug Delivery ◽  
Locust Bean ◽  
Ceratonia Siliqua L

Hydrodynamically Balanced systems have wide development as they have achieved the parameters of modern drug delivery system, it is a type of system which owes very tremendous and curative benefits for the delivery of oral controlled release dosage forms and have wide properties in many aspects such as its main role is to maintain the effective concentration in the system for longer period of time. To reduce the gastric mucosal irritation due to the presence of synthetic polymers, being a natural polymer incorporation of Plantago ovate (Psyllium Husk) could ease out the mucosal irritation in the gastric region. Due to its properties such as a rate-controlling polymer possessing a very good quality of swelling and good gelling nature, and also incorporated as a matrix-forming agent basically in the modified release formulation. Locust bean gum can be used as sustained-release carriers and release modifiers for the delivery of drugs. It is a neutral plant galactomannan extracted from the seeds (kernels) of the carob tree Ceratonia siliqua L fabaceae. Nowadays it is focussing polymer and a lot of researchers are focussing on exploring the potential in topical drug delivery, colonic drug delivery, oral sustained drug delivery, ocular drug delivery, buccal drug delivery.

Development of Solid-Self Micron Emulsifying Drug Delivery Systems

2013 ◽  
Vol 6 (2) ◽  
pp. 2014-2021
Author(s):  
Preethi Sudheer ◽  
Koushik Y ◽  
Satish P ◽  
Uma Shankar M S ◽  
R S Thakur
Keyword(s):  
Drug Delivery ◽  
Systemic Circulation ◽  
Water Soluble ◽  
Future Research ◽  
Steady Increase ◽  
Liquid Form ◽  
Lipophilic Compounds ◽  
Modern Drug ◽  
Pharmaceutical Scientist ◽  
Pharmacologically Active

As a consequence of modern drug discovery techniques, there has been a steady increase in the number of new pharmacologically active lipophilic compounds that are poorly water soluble and solubility is one of the most important parameter to achieve desired concentration of drug in systemic circulation for therapeutic response. It is a great challenge for pharmaceutical scientist to convert those molecules into orally administered formulation with sufficient bioavailability.  Among the several approaches to improve oral bioavailability of these molecules, Self-micron emulsifying drug delivery system (SMEDDS) is one of the approaches usually used to improve the bioavailability of hydrophobic drugs. However, conventional SMEDDS are mostly prepared in a liquid form, which can have several disadvantages. Accordingly, solid SMEDDS (S-SMEDDS) prepared by solidification of liquid/semisolid self-micron emulsifying (SME) ingredients into powders have gained popularity. This article provides an overview of the recent advancements in S-SMEDDS such as methodology, techniques and future research directions.

scholarly journals Focused ultrasound in neuro-oncology: the role of the Focused Ultrasound Foundation in driving adoption and innovation

2021 ◽  
Author(s):  
Emily C. Whipple ◽  
Camille A. Favero ◽  
Neal F. Kassell
Keyword(s):  
Drug Delivery ◽  
Brain Tumors ◽  
Focused Ultrasound ◽  
Clinical Evidence ◽  
Neurological Injury ◽  
High Concentration ◽  
Potential Applications ◽  
Tumor Agent

Abstract Introduction Intra-arterial (lA) delivery of therapeutic agents across the blood-brain barrier (BBB) is an evolving strategy which enables the distribution of high concentration therapeutics through a targeted vascular territory, while potentially limiting systemic toxicity. Studies have demonstrated lA methods to be safe and efficacious for a variety of therapeutics. However, further characterization of the clinical efficacy of lA therapy for the treatment of brain tumors and refinement of its potential applications are necessary. Methods We have reviewed the preclinical and clinical evidence supporting superselective intraarterial cerebral infusion (SSJACI) with BBB disruption for the treatment of brain tumors. In addition, we review ongoing clinical trials expanding the applicability and investigating the efficacy of lA therapy for the treatment of brain tumors. Results Trends in recent studies have embraced the use of SSIACI and less neurotoxic chemotherapies. The majority of trials continue to use mannitol as the preferred method of hyperosmolar BBB disruption. Recent preclinical and preliminary human investigations into the lA delivery of Bevacizumab have demonstrated its safety and efficacy as an anti-tumor agent both alone and in combination with chemotherapy. Conclusion lA drug delivery may significantly affect the way treatment are delivered to patients with brain tumors, and in particular GBM. With refinement and standardization of the techniques of lA drug delivery, improved drug selection and formulations, and the development of methods to minimize treatment-related neurological injury, lA therapy may offer significant benefits for the treatment of brain tumors.

scholarly journals Characterization of ultrasound-mediated delivery of trastuzumab to normal and pathologic spinal cord tissue

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paige Smith ◽  
Natalia Ogrodnik ◽  
Janani Satkunarajah ◽  
Meaghan A. O’Reilly
Keyword(s):  
Drug Delivery ◽  
Spinal Cord ◽  
Focused Ultrasound ◽  
Healthy Tissue ◽  
Spinal Cord Tissue ◽  
Sprague Dawley ◽  
Intense Staining ◽  
Her2 Breast Cancer ◽  
Sprague Dawley Rats ◽  
Blood Spinal Cord Barrier

AbstractExtensive studies on focused ultrasound (FUS)-mediated drug delivery through the blood–brain barrier have been published, yet little work has been published on FUS-mediated drug delivery through the blood-spinal cord barrier (BSCB). This work aims to quantify the delivery of the monoclonal antibody trastuzumab to rat spinal cord tissue and characterize its distribution within a model of leptomeningeal metastases. 10 healthy Sprague–Dawley rats were treated with FUS + trastuzumab and sacrificed at 2-h or 24-h post-FUS. A human IgG ELISA (Abcam) was used to measure trastuzumab concentration and a 12 ± fivefold increase was seen in treated tissue over control tissue at 2 h versus no increase at 24 h. Three athymic nude rats were inoculated with MDA-MB-231-H2N HER2 + breast cancer cells between the meninges in the thoracic region of the spinal cord and treated with FUS + trastuzumab. Immunohistochemistry was performed to visualize trastuzumab delivery, and semi-quantitative analysis revealed similar or more intense staining in tumor tissue compared to healthy tissue suggesting a comparable or greater concentration of trastuzumab was achieved. FUS can increase the permeability of the BSCB, improving drug delivery to specifically targeted regions of healthy and pathologic tissue in the spinal cord. The achieved concentrations within the healthy tissue are comparable to those reported in the brain.

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.

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