scholarly journals Computational Modeling of Combination of Magnetic Hyperthermia and Temperature-Sensitive Liposome for Controlled Drug Release in Solid Tumor

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 35
Author(s):  
Masoud H. H. Tehrani ◽  
M. Soltani ◽  
Farshad Moradi Kashkooli ◽  
Mohammadreza Mahmoudi ◽  
Kaamran Raahemifar
Keyword(s):  
Side Effects ◽  
Combination Therapy ◽  
Pore Size ◽  
Solid Tumor ◽  
Vessel Wall ◽  
Therapeutic Potential ◽  
Controlled Drug Release ◽  
Magnetic Hyperthermia ◽  
Time Interval ◽  
Temperature Sensitive

Combination therapy, a treatment modality that combines two or more therapeutic methods, provides a novel pathway for cancer treatment, as it targets the region of interest (ROI) in a characteristically synergistic or additive manner. To date, liposomes are the only nano-drug delivery platforms that have been used in clinical trials. Here, we speculated that it could be promising to improve treatment efficacy and reduce side effects by intravenous administration of thermo-sensitive liposomes loaded with doxorubicin (TSL-Dox) during magnetic hyperthermia (MHT). A multi-scale computational model using the finite element method was developed to simulate both MHT and temperature-sensitive liposome (TSL) delivery to a solid tumor to obtain spatial drug concentration maps and temperature profiles. The results showed that the killing rate of MHT alone was about 15%, which increased to 50% using the suggested combination therapy. The results also revealed that this combination treatment increased the fraction of killed cells (FKCs) inside the tumor compared to conventional chemotherapy by 15% in addition to reducing side effects. Furthermore, the impacts of vessel wall pore size, the time interval between TSL delivery and MHT, and the initial dose of TSLs were also investigated. A considerable reduction in drug accumulation was observed in the tumor by decreasing the vessel wall pore size of the tumor. The results also revealed that the treatment procedure plays an essential role in the therapeutic potential of anti-cancer drugs. The results suggest that the administration of MHT can be beneficial in the TSL delivery system and that it can be employed as a guideline for upcoming preclinical studies.

Synthesis and Investigation of Therapeutic Potential of Isoform-Specific HDAC8 Inhibitors for the Treatment of Cutaneous T Cell Lymphoma

2019 ◽  
Vol 19 (7) ◽  
pp. 916-934 ◽  
Author(s):  
Appavoo Umamaheswari ◽  
Ayarivan Puratchikody ◽  
Natarajan Hari
Keyword(s):  
Side Effects ◽  
Inhibitory Activity ◽  
Hydroxamic Acid ◽  
Histone Deacetylase Inhibitors ◽  
Therapeutic Potential ◽  
In Vitro Assays ◽  
Normal Cells ◽  
Standard Drug ◽  
In Silico Studies ◽  
Hdac8 Inhibitors

Background:The available treatment option for any type of cancer including CTCL is chemotherapy and radiation therapy which indiscriminately persuade on the normal cells. One way out for selective destruction of CTCL cells without damaging normal cells is the use of histone deacetylase inhibitors (HDACi). Despite promising results in the treatment of CTCL, these HDACi have shown a broadband inhibition profile, moderately selective for one HDAC class but not for a particular isotype. The prevalence of drug-induced side effects leaves open a narrow window of speculation that the decreased therapeutic efficacy and observed side effects may be most likely due to non specific HDAC isoform inhibition. The aim of this paper is to synthesis and evaluates HDAC8 isoform specific inhibitors.Methods:Based on the preliminary report on the design and in silico studies of 52 hydroxamic acid derivatives bearing multi-substituent heteroaromatic rings with chiral amine linker, five compounds were shortlisted and synthesized by microwave assisted approach and high yielding synthetic protocol. A series of in vitro assays in addition to HDAC8 inhibitory activity was used to evaluate the synthesised compounds.Results:Inhibitors 1e, 2e, 3e, 4e and 5e exerted the anti-proliferative activities against CTCL cell lines at 20- 100 µM concentrations. Both the pyrimidine- and pyridine-based probes exhibited μM inhibitory activity against HDAC8. The pyrimidine-based probe 1e displayed remarkable HDAC8 selectivity superior to that of the standard drug, SAHA with an IC50 at 0.1µM.Conclusion:Our study demonstrated that simple modifications at different portions of pharmacophore in the hydroxamic acid analogues are effective for improving both HDAC8 inhibitory activity and isoform selectivity. Potent and highly isoform-selective HDAC8 inhibitors were identified. These findings would be expedient for further development of HDAC8-selective inhibitors.

scholarly journals Magnetic hyperthermia controlled drug release in the GI tract: solving the problem of detection

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Joseph C. Bear ◽  
P. Stephen Patrick ◽  
Alfred Casson ◽  
Paul Southern ◽  
Fang-Yu Lin ◽  
...  
Keyword(s):  
Drug Release ◽  
Controlled Drug Release ◽  
Magnetic Hyperthermia ◽  
Gi Tract

scholarly journals Polymeric Mesoporous Silica Nanoparticles for Enhanced Delivery of 5-Fluorouracil In Vitro

Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 288 ◽  
Author(s):  
Thashini Moodley ◽  
Moganavelli Singh
Keyword(s):  
Side Effects ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Therapeutic Potential ◽  
Mesoporous Silica Nanoparticles ◽  
Drug Loading ◽  
Hek293 Cells ◽  
Cancer Drug ◽  
Delivery Vehicles

There is a need for the improvement of conventional cancer treatment strategies by incorporation of targeted and non-invasive procedures aimed to reduce side-effects, drug resistance, and recurrent metastases. The anti-cancer drug, 5-fluorouracil (5-FU), is linked to a variety of induced-systemic toxicities due to its lack of specificity and potent administration regimens, necessitating the development of delivery vehicles that can enhance its therapeutic potential, while minimizing associated side-effects. Polymeric mesoporous silica nanoparticles (MSNs) have gained popularity as delivery vehicles due to their high loading capacities, biocompatibility, and good pharmacokinetics. MSNs produced in this study were functionalized with the biocompatible polymers, chitosan, and poly(ethylene)glycol to produce monodisperse NPs of 36–65 nm, with a large surface area of 710.36 m2/g, large pore volume, diameter spanning 9.8 nm, and a favorable zeta potential allowing for stability and enhanced uptake of 5-FU. Significant drug loading (0.15–0.18 mg5FU/mgmsn), controlled release profiles (15–65%) over 72 hours, and cell specific cytotoxicity in cancer cells (Caco-2, MCF-7, and HeLa) with reduced cell viability (≥50%) over the non-cancer (HEK293) cells were established. Overall, these 5FU-MSN formulations have been shown to be safe and effective delivery systems in vitro, with potential for in vivo applications.

scholarly journals Combination Therapy with Continuous Three-in-One Femoral Nerve Block and Periarticular Multimodal Drug Infiltration after Total Hip Arthroplasty

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Tomonori Tetsunaga ◽  
Tomoko Tetsunaga ◽  
Kazuo Fujiwara ◽  
Hirosuke Endo ◽  
Toshifumi Ozaki
Keyword(s):  
Side Effects ◽  
Pain Relief ◽  
Total Hip Arthroplasty ◽  
Combination Therapy ◽  
Hospital Stay ◽  
Nerve Block ◽  
Hip Arthroplasty ◽  
Femoral Nerve Block ◽  
Femoral Nerve ◽  
Length Of Hospital Stay

Background. Various postoperative pain relief modalities, including continuous femoral nerve block (CFNB), local infiltration analgesia (LIA), and combination therapy, have been reported for total knee arthroplasty. However, no studies have compared CFNB with LIA for total hip arthroplasty (THA). The aim of this study was to compare the efficacy of CFNB versus LIA after THA. Methods. We retrospectively reviewed the postoperative outcomes of 93 THA patients (20 men, 73 women; mean age 69.2 years). Patients were divided into three groups according to postoperative analgesic technique: CFNB, LIA, or combined CFNB+LIA. We measured the following postoperative outcome parameters: visual analog scale (VAS) for pain at rest, supplemental analgesia, side effects, mobilization, length of hospital stay, and Harris Hip Score (HHS). Results. The CFNB+LIA group had significantly lower VAS pain scores than the CFNB and LIA groups on postoperative day 1. There were no significant differences among the three groups in use of supplemental analgesia, side effects, mobilization, length of hospital stay, or HHS at 3 months after THA. Conclusions. Although there were no clinically significant differences in outcomes among the three groups, combination therapy with CFNB and LIA provided better pain relief after THA than CFNB or LIA alone, with few side effects.

Combination Therapy of Extrapyramidal Disease with Trihexyphenidyl and L-Dopa

1979 ◽  
Vol 7 (1) ◽  
pp. 19-28 ◽  
Author(s):  
H Hökendorf
Keyword(s):  
Side Effects ◽  
Combination Therapy ◽  
Motor System ◽  
Good Control ◽  
Decarboxylase Inhibitor ◽  
System Disease ◽  
Extrapyramidal Disease ◽  
Extrapyramidal Motor

An electromyographic method was used to study the effect of combination therapy with L-dopa and trihexyphenidyl on tremor in thirty patients suffering from extrapyramidal motor system disease. In this method tremor activity was measured and documented so that the course of the disease could be followed objectively. L-dopa alone was slightly more effective against tremor than was trihexyphenidyl alone. The combination of the two drugs was more effective than either drug used alone, and its side-effects were mild and definitely fewer than had been reported with L-dopa combined with a decarboxylase inhibitor. Good control of tremor with L-dopa and trihexyphenidyl was obtained clinically and verified electromyographically.

scholarly journals Molecular and Therapeutic Potential and Toxicity of Valproic Acid

2010 ◽  
Vol 2010 ◽  
pp. 1-18 ◽  
Author(s):  
Sébastien Chateauvieux ◽  
Franck Morceau ◽  
Mario Dicato ◽  
Marc Diederich
Keyword(s):  
Valproic Acid ◽  
Clinical Trials ◽  
Side Effects ◽  
Histone Deacetylase Inhibitors ◽  
Short Chain Fatty Acid ◽  
Therapeutic Potential ◽  
Mood Stabilizer ◽  
Chain Fatty Acid ◽  
Histone Deacetylation ◽  
Transcription Sites

Valproic acid (VPA), a branched short-chain fatty acid, is widely used as an antiepileptic drug and a mood stabilizer. Antiepileptic properties have been attributed to inhibition of Gamma Amino Butyrate (GABA) transaminobutyrate and of ion channels. VPA was recently classified among the Histone Deacetylase Inhibitors, acting directly at the level of gene transcription by inhibiting histone deacetylation and making transcription sites more accessible. VPA is a widely used drug, particularly for children suffering from epilepsy. Due to the increasing number of clinical trials involving VPA, and interesting results obtained, this molecule will be implicated in an increasing number of therapies. However side effects of VPA are substantially described in the literature whereas they are poorly discussed in articles focusing on its therapeutic use. This paper aims to give an overview of the different clinical-trials involving VPA and its side effects encountered during treatment as well as its molecular properties.

DNA-capped Fe3O4/SiO2 magnetic mesoporous silica nanoparticles for potential controlled drug release and hyperthermia

RSC Advances ◽  
2015 ◽  
Vol 5 (29) ◽  
pp. 22365-22372 ◽  
Author(s):  
Yufang Zhu ◽  
Cuilian Tao
Keyword(s):  
Drug Release ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Mesoporous Silica Nanoparticles ◽  
Potential Temperature ◽  
Controlled Drug Release ◽  
Magnetic Hyperthermia ◽  
Temperature Controlled ◽  
Magnetic Mesoporous Silica

DNA-capped Fe3O4/SiO2 magnetic mesoporous silica (MMS) nanoparticles were developed for potential temperature controlled drug release and magnetic hyperthermia.

scholarly journals Opening the time window

2019 ◽  
Vol 39 (12) ◽  
pp. 2539-2540 ◽  
Author(s):  
Klaus van Leyen ◽  
Xiaoying Wang ◽  
Magdy Selim ◽  
Eng H Lo
Keyword(s):  
Side Effects ◽  
Combination Therapy ◽  
Patient Selection ◽  
Endovascular Therapy ◽  
Perfusion Imaging ◽  
Paradigm Shift ◽  
Time Window ◽  
Stroke Therapy ◽  
Image Guided ◽  
Tissue Plasminogen

The recently completed EXTEND trial tested the idea that tissue plasminogen activator thrombolysis can be safely extended up to 9 h after stroke onset if automated perfusion imaging indicates the presence of a salvageable penumbra. This important trial contributes to an ongoing paradigm shift for stroke therapy. Combined with the introduction of endovascular therapy, image-guided patient selection is expanding the toolbox of the stroke practitioner. At the same time, pushing the limits of reperfusion has raised important questions about mechanisms to pursue for combination therapy as well as potential approaches to mitigate side effects and optimize treatments for patients with various co-morbidities.

scholarly journals The Effect of Systemic Methotrexate and Cyclosporine Combination Therapy inPsoriasis Vulgaris Patients in Bandung, Indonesia

2021 ◽  
Vol 33 (3) ◽  
pp. 200
Author(s):  
Oki Suwarsa ◽  
Fatima Aulia Khairani ◽  
Syawalika Ulya Isneny ◽  
Erda Avriyanti ◽  
Hartati Purbo Dharmadji ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Side Effects ◽  
Adverse Effects ◽  
Combination Therapy ◽  
Combination Treatment ◽  
Psoriasis Vulgaris ◽  
Severity Index ◽  
Dermatology Clinic ◽  
Significant Difference ◽  
Pasi Score

Background: Methotrexate (MTX) and cyclosporine have been used as effective systemic mono-therapy for psoriasis. Several factors are considered to switch monotherapy to combination therapy because monotherapy is no longer effective and has higher side effects. Hence,clinicians have avoided systemic therapy combinations due to its toxicity. However, some studies showed that this combination therapy could be usedeffectively for psoriasis patients. Purpose: This study aimed to analyze the efficacy and adverse effects of systemic MTX and cyclosporine combination therapy in Indonesian psoriasis vulgaris patients. Methods: The retrospective study assessed the effectiveness of 3 monthsmono-therapyand combination therapy of systemic MTX and cyclosporine in psoriasisvulgaris patients from 2016–2017 in Dermatology Clinic, Dr. Hasan Sadikin Hospital, Bandung, West Java, Indonesia. Result: Psoriasis area and severity index (PASI) score 90 were achieved in the group MTX (50%) and cyclosporine group (50%), while none in the combination group.However, eight patients (50%) in group MTX and cyclosporine reached the primary endpoint of PASI 50. One patient in cyclosporine group had adverse effects on kidney profiles. Nonetheless, other patients had no biochemical changes. But, there was no significant difference in the change of PASI between each group (p=0.102). Conclusion: We propose that combination therapy of MTX and cyclosporine is relatively safe and efficacious in treating Indonesian psoriasis vulgaris patients. This combination treatment isas effective as MTX or cyclosporinemono-therapy.

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