scholarly journals Optimization and Development of Selective Histone Deacetylase Inhibitor (MPT0B291)-Loaded Albumin Nanoparticles for Anticancer Therapy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1728
Author(s):  
Athika Darumas Putri ◽  
Pai-Shan Chen ◽  
Yu-Lin Su ◽  
Jia-Pei Lin ◽  
Jing-Ping Liou ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Water Solubility ◽  
Human Cancer ◽  
Maximum Tolerated Dose ◽  
Free Drug ◽  
Pharmacokinetic Studies ◽  
Anticancer Activities ◽  
Drug Solution

Histone deacetylase (HDAC) inhibitors have emerged as a new class of antitumor agent for various types of tumors. MPT0B291, a novel selective inhibitor of HDAC6, demonstrated significant antiproliferative activity in various human cancer cell types. However, MPT0B291 has very low water solubility, which limits its clinical use for cancer therapy. In the current study, MPT0B291 was encapsulated in human serum albumin (HSA), and its anticancer activities were investigated. Nanoparticles (NPs) were prepared using two-stage emulsification resulting in 100~200-nm NPs with a fine size distribution (polydispersity index of <0.3). The in vitro drug release profiles of MPT0B291-loaded HSA NPs presented sustained-release properties. The cytotoxic effect on MIA PaCa-2 human pancreatic carcinoma cells was found to be similar to MPT0B291-loaded HSA NPs and the free-drug group. The albumin-based formulation provided a higher maximum tolerated dose than that of a drug solution with reduced toxicity toward normal cells. Furthermore, in vivo pharmacokinetic studies demonstrated an effective increase (5~8-fold) in the bioavailability of NPs containing MPT0B291 loaded in HSA compared to the free-drug solution with an extended circulation time (t1/2) leading to significantly enhanced efficacy of anticancer treatment.

scholarly journals Nose to Brain Delivery of Phenytoin Sodium Loaded Nano Lipid Carriers: Formulation, Drug Release, Permeation and In Vivo Pharmacokinetic Studies

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1640
Author(s):  
Sreeja C. Nair ◽  
Kollencheri Puthenveettil Vinayan ◽  
Sabitha Mangalathillam
Keyword(s):  
Drug Release ◽  
Olfactory Epithelium ◽  
Drug Transport ◽  
Ex Vivo ◽  
Medical Attention ◽  
Pharmacokinetic Studies ◽  
Phenytoin Sodium ◽  
Drug Solution

An acute epileptic seizure is a seizure emergency fatal condition that requires immediate medical attention. IV phenytoin sodium remains the second line therapeutic agent for the immediate treatment of status epilepticus. Phenytoin sodium formulated as nanolipid carriers (NLCs) seems to be promising as an intranasal delivery system for controlling acute seizures. Three different nanosized phenytoin sodium loaded NLCs (<50 nm, 50–100 nm and >100 nm) were prepared by melt emulsification and was further characterised. In vitro drug release studies showed immediate drug release from phenytoin sodium loaded NLCs of <50 nm size, which is highly essential for acute seizure control. The ex vivo permeation study indicated greater permeation from <50 nm sized NLC through the olfactory epithelium compared to thecontrol drug solution. Invivo pharmacokinetic studies revealed higher drug concentration in CSF/brain within 5 min upon intranasal administration of <50 nm sized phenytoin sodium NLCs than the control drug solution and marketed IV phenytoin sodium, indicating direct and rapid nose to brain drug transport through the olfactory epithelium. The study has shown that formulation strategies can enhance olfactory uptake, and phenytoin sodium NLCs of desired particle sizes (<50 nm) offer promising potential for nose to brain direct delivery of phenytoin sodium in treating acute epileptic seizures.

scholarly journals Use of Novel Polyurethane Microspheres in a Curcumin Delivery System

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Yongmei Hu ◽  
Qingshan Li ◽  
Wei Hong ◽  
Guangzhong Xing ◽  
Qilong Jiang ◽  
...  
Keyword(s):  
Water Solubility ◽  
Pharmacokinetic Studies ◽  
Pharmacological Effects ◽  
Ph Variation ◽  
Wide Range ◽  
Carboxymethyl Cellulose Sodium ◽  
The Stability ◽  
Scanning Electron

Despite having a wide range of beneficial pharmacological effects, curcumin is characterized by poor water solubility and absorption. In this study, novel polyurethane microspheres containing curcumin (Cur-PUMs) were prepared using carboxymethyl cellulose sodium to improve the bioavailability and prolong the retention time of curcumin. The prepared Cur-PUMs were characterized by Fourier transform infrared spectroscopy, scanning electron microscope, and ultraviolet spectrophotometer. The sustained-release effects of Cur-PUMs were demonstrated using stability testsin vitroandin vivopharmacokinetic studies following oral administration. We found that the stability of Cur-PUMs was strongly affected by pH variation. Further, compared with free curcumin, Cur-PUMs showed significantly improved maximum concentration and half-life.

scholarly journals Health Benefits and Pharmacological Properties of Carvone

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1803
Author(s):  
Abdelhakim Bouyahya ◽  
Hamza Mechchate ◽  
Taoufiq Benali ◽  
Rokia Ghchime ◽  
Saoulajan Charfi ◽  
...  
Keyword(s):  
Extraction Methods ◽  
Mechanisms Of Action ◽  
Ultrastructural Changes ◽  
Pharmacokinetic Studies ◽  
Pharmacological Properties ◽  
Anticancer Activities ◽  
Therapeutic Drugs ◽  
Anti Inflammatory

Carvone is a monoterpene ketone contained in the essential oils of several aromatic and medicinal plants of the Lamiaceae and Asteraceae families. From aromatic plants, this monoterpene is secreted at different concentrations depending on the species, the parts used, and the extraction methods. Currently, pharmacological investigations showed that carvone exhibits multiple pharmacological properties such as antibacterial, antifungal, antiparasitic, antineuraminidase, antioxidant, anti-inflammatory, and anticancer activities. These studies were carried out in vitro and in vivo and involved a great deal of knowledge on the mechanisms of action. Indeed, the antimicrobial effects are related to the action of carvone on the cell membrane and to ultrastructural changes, while the anti-inflammatory, antidiabetic, and anticancer effects involve the action on cellular and molecular targets such as inducing of apoptosis, autophagy, and senescence. With its multiple mechanisms, carvone can be considered as natural compounds to develop therapeutic drugs. However, other investigations regarding its precise mechanisms of action as well as its acute and chronic toxicities are needed to validate its applications. Therefore, this review discusses the principal studies investigating the pharmacological properties of carvone, and the mechanism of action underlying some of these properties. Moreover, further investigations of major pharmacodynamic and pharmacokinetic studies were also suggested.

scholarly journals In-silico investigation of curcumin drug-likeness, gene-targets and prognostic relevance of the targets in panels of human cancer cohorts

2021 ◽  
Vol 14 (1) ◽  
pp. 037-046
Author(s):  
David B Oshevire ◽  
Aishatu Mustapha ◽  
Blessing U. Alozieuwa ◽  
Hassana H. Badeggi ◽  
Abdulfatai Ismail ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Human Cancer ◽  
Treatment Modalities ◽  
Drug Candidate ◽  
Anticancer Activities ◽  
Multiple Cancer ◽  
In Vivo Models ◽  
Lipinski’S Rule

Despite advancements in diagnostic and standard treatment modalities, cancer survival rate remains disappointing globally. It has however, been recognized that exploring the therapeutic properties of secondary metabolite from natural products may alleviate the problems of drug resistance and toxicity that besiege the conventional therapies, and hence improve the overall prognosis of cancer patient. To this end curcumin, a polyphenolic natural compound has been widely studied for it anticancer activities in in vitro and in vivo models. Computational technology has significantly improved the success rate of drug discovery and development, hence, it has become a widely explore tool in drug candidate identification. In this study we used computational approached to identify 12 genes that are potential druggable candidate for curcumin. The genes identified were found to be enriched in cancer and drug resistance associated signaling pathways. Interestingly, the top 3 identified genes; Microtubule-associated protein tau (MAPT), Toll-like receptor 9 (TLR9) and Tyrosyl-DNA phosphodiesterase 1 (TDP1) were observed to be over expressed in multiple cancer cohorts and were associated with poor prognoses of the patients. Curcumin has good physicochemical, bioavailability and ADMET properties. Importantly, it met the Lipinski's Rule of 5 for drug likeness and thus worthy of further in vitro and in vivo confirmation studies.

Evaluation of the toxicity and efficacy of paclitaxel nanoencapsulated with polyethyloxazoline polymers.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13538-e13538
Author(s):  
Ray Yin ◽  
Jing Pan ◽  
Bingsen Zhou ◽  
Yubei Zhang ◽  
Jeffrey Dougherty ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cell Lines ◽  
Lung Tumor ◽  
Human Cancer ◽  
Drug Loading ◽  
Maximum Tolerated Dose ◽  
Negative Control ◽  
Branched Polymers

e13538 Background: Paclitaxel’s antineoplastic activity is limited by its solubility and toxicity. Encapsulation with polyethyloxazoline (PEOX) branched polymers can increase its solubility, decrease toxicity and enhance its antitumor efficacy. Methods: Paclitaxel was mixed with PEOX-based branched polymers at drug loading percentages of 11 - 17% to form nanoparticles (< 90 nm in diameter). The product was purified and lyophilized as a white powder, designated FID-007. Its cytotoxicity was tested on normal human fibroblast cells and cell lines for human lung (A549), triple negative breast (MDA-MB-231) and ovarian (OV-90) cancers. Commercial paclitaxel drugs, Taxol and Abraxane, were similarly tested. Maximum tolerated dose (MTD) of the three drugs were determined in CD-1 mice. FID-007’s efficacy in controlling tumor growth was compared to the other drugs in vivo using xenograft tumor models in Scid mice with the three human cancer cell lines (20 mice per cancer). Saline and polymer were used as negative control treatments. Results: FID-007, Taxol and Abraxane showed similar cytotoxicity to all cancers.FID-007 was > 10-fold less active in normal fibroblasts. The single dose MTD in CD-1 mice was < 30 mg/kg for Taxol, 175 mg/kg for FID-007 and >180 mg/kg for Abraxane. FID-007 exhibited the best efficacy in controlling tumor growth in mice compared to Taxol and Abraxane with the three human cancers. Results from the lung tumor study are presented in the Table. Conclusions: Encapsulation with PEOX-based polymers reduced the toxicity and significantly improved the efficacy of paclitaxel in controlling tumor growth in vitro and in vivo. [Table: see text]

scholarly journals Therapeutic Efficacy and Biodistribution of Paclitaxel-Bound Amphiphilic Cyclodextrin Nanoparticles: Analyses in 3D Tumor Culture and Tumor-Bearing Animals In Vivo

Nanomaterials ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 515
Author(s):  
Gamze Varan ◽  
Cem Varan ◽  
Süleyman Can Öztürk ◽  
Juan M. Benito ◽  
Güneş Esendağlı ◽  
...  
Keyword(s):  
Water Solubility ◽  
Cardiac Toxicity ◽  
Polymeric Nanoparticles ◽  
Clinical Success ◽  
Surface Charges ◽  
Cancer Treatments ◽  
Amphiphilic Cyclodextrin ◽  
Drug Solution

The uniqueness of paclitaxel’s antimitotic action mechanism has fueled research toward its application in more effective and safer cancer treatments. However, the low water solubility, recrystallization, and side effects hinder the clinical success of classic paclitaxel chemotherapy. The aim of this study was to evaluate the in vivo efficacy and biodistribution of paclitaxel encapsulated in injectable amphiphilic cyclodextrin nanoparticles of different surface charges. It was found that paclitaxel-loaded amphiphilic cyclodextrin nanoparticles showed an antitumoral effect earlier than the drug solution. Moreover, the blank nanoparticles reduced the tumor growth with a similar trend to the paclitaxel solution. At 24 h, the nanoparticles had not accumulated in the heart and lungs according to the biodistribution assessed by in vivo imaging. Therefore, our results indicated that the amphiphilic cyclodextrin nanoparticles are potentially devoid of cardiac toxicity, which limits the clinical use and commercialization of certain polymeric nanoparticles. In conclusion, the amphiphilic cyclodextrin nanoparticles with different surface charge increased the efficiency of paclitaxel in vitro and in vivo. Cyclodextrin nanoparticles could be a good candidate vehicle for intravenous paclitaxel delivery.

Pinus massoniana Bark Extract: Structure–Activity Relationship and Biomedical Potentials

2016 ◽  
Vol 44 (08) ◽  
pp. 1559-1577 ◽  
Author(s):  
Jiao Feng ◽  
Xiao-Lu Zhang ◽  
Ying-Ya Li ◽  
Ying-Yu Cui ◽  
Yi-Han Chen
Keyword(s):  
Water Solubility ◽  
Condensed Tannin ◽  
Radical Scavenging ◽  
Reaction System ◽  
Pinus Massoniana ◽  
Degree Of Polymerization ◽  
Bark Extract ◽  
Anticancer Activities

Proanthocyanidins (PAs) belong to the condensed tannin subfamily of natural flavonoids. Recent studies have shown that the main bioactive compounds of Pinus massoniana bark extract (PMBE) are PAs, especially the proanthocyanidins B series, which play important roles in cell cycle arrest, apoptosis induction and migration inhibition of cancer cells in vivo and in vitro. PA-Bs are mixtures of oligomers and polymers composed of flavan-3-ol, and the relationship between their structure and corresponding biomedical potentials is summarized in this paper. The hydroxyl at certain positions or the linkage between different carbon atoms of different rings determines or affects their anti-oxidant and free radical scavenging bioactivities. The degree of polymerization and the water solubility of the reaction system also influence their biomedical potential. Taken together, PMBE has a promising future in clinical drug development as a candidate anticancer drug and as a food additive to prevent tumorigenesis. We hope this review will encourage interested researchers to conduct further preclinical and clinical studies to evaluate the anticancer activities of PMBE, its active constituents and their derivatives.

Nanocurcumin: A Double-Edged Sword for Microcancers

2020 ◽  
Vol 26 (45) ◽  
pp. 5783-5792
Author(s):  
Kholood Abid Janjua ◽  
Adeeb Shehzad ◽  
Raheem Shahzad ◽  
Salman Ul Islam ◽  
Mazhar Ul Islam
Keyword(s):  
Intracellular Signaling ◽  
Dosage Forms ◽  
The Body ◽  
In Vivo Studies ◽  
Mrna Levels ◽  
Anticancer Activities ◽  
Road Map ◽  
Anticancer Effects

There is compelling evidence that drug molecules isolated from natural sources are hindered by low systemic bioavailability, poor absorption, and rapid elimination from the human body. Novel approaches are urgently needed that could enhance the retention time as well as the efficacy of natural products in the body. Among the various adopted approaches to meet this ever-increasing demand, nanoformulations show the most fascinating way of improving the bioavailability of dietary phytochemicals through modifying their pharmacokinetics and pharmacodynamics. Curcumin, a yellowish pigment isolated from dried ground rhizomes of turmeric, exhibits tremendous pharmacological effects, including anticancer activities. Several in vitro and in vivo studies have shown that curcumin mediates anticancer effects through the modulation (upregulation and/or downregulations) of several intracellular signaling pathways both at protein and mRNA levels. Scientists have introduced multiple modern techniques and novel dosage forms for enhancing the delivery, bioavailability, and efficacy of curcumin in the treatment of various malignancies. These novel dosage forms include nanoparticles, liposomes, micelles, phospholipids, and curcumin-encapsulated polymer nanoparticles. Nanocurcumin has shown improved anticancer effects compared to conventional curcumin formulations. This review discusses the underlying molecular mechanism of various nanoformulations of curcumin for the treatment of different cancers. We hope that this study will make a road map for preclinical and clinical investigations of cancer and recommend nano curcumin as a drug of choice for cancer therapy.

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