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Cytotoxic drug safety

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https://www.readbyqxmd.com/read/29042604/placenta-specific1-plac1-is-a-potential-target-for-antibody-drug-conjugate-based-prostate-cancer-immunotherapy
#1
Mohammad-Reza Nejadmoghaddam, Amir-Hassan Zarnani, Ramin Ghahremanzadeh, Roya Ghods, Jafar Mahmoudian, Maryam Yousefi, Mahboobeh Nazari, Mohammad Hossein Ghahremani, Maryam Abolhasani, Ali Anissian, Morteza Mahmoudi, Rassoul Dinarvand
Our recent findings strongly support the idea of PLAC1 being as a potential immunotherapeutic target in prostate cancer (PCa). Here, we have generated and evaluated an anti-placenta-specific1 (PLAC1)-based antibody drug conjugate (ADC) for targeted immunotherapy of PCa. Prostate cancer cells express considerable levels of PLAC1. The Anti-PLAC1 clone, 2H12C12, showed high reactivity with recombinant PLAC1 and selectivity recognized PLAC1 in prostate cancer cells but not in LS180 cells, the negative control. PLAC1 binding induced rapid internalization of the antibody within a few minutes which reached to about 50% after 15 min and almost completed within an hour...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29034213/a-promising-listeria-vectored-vaccine-induces-th1-type-immune-responses-and-confers-protection-against-tuberculosis
#2
Yuelan Yin, Kai Lian, Dan Zhao, Chengwu Tao, Xiang Chen, Weijun Tan, Xiaobo Wang, Zhengzhong Xu, Maozhi Hu, Yan Rao, Xiaohui Zhou, Zhiming Pan, Xiaoming Zhang, Xin'an Jiao
Deaths associated with tuberculosis (TB) is rising and accounted for 1.4 million deaths in 2015 many of which were due to drug-resistant bacteria. Vaccines represent an important medical intervention, but the current Bacilli Calmette-Guerin (BCG) vaccine is not ideal for the protection of teenagers and adults. Therefore, a safe and effective vaccine is urgently needed. In this study, we designed a novel vaccine using an attenuated Listeria monocytogenes strain carrying fusion antigen FbpB-ESAT-6 (rLM) and characterized its safety and protective efficacy against Mycobacterium tuberculosis (M...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29027591/clinical-toxicity-of-antibody-drug-conjugates-a-meta-analysis-of-payloads
#3
REVIEW
Joanna C Masters, Dana J Nickens, Dawei Xuan, Ronald L Shazer, Michael Amantea
Background Antibody drug conjugates (ADCs) utilize a monoclonal antibody to deliver a cytotoxic payload specifically to tumor cells, limiting exposure to healthy tissues. Major clinical toxicities of ADCs include hematologic, hepatic, neurologic, and ophthalmic events, which are often dose-limiting. These events may be off-target effects caused by premature release of payload in circulation. A meta-analysis was performed to summarize key clinical safety data for ADCs by payload, and data permitting, establish a dose-response model for toxicity incidence as a function of payload, dose/regimen, and cancer type...
October 13, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28986321/an-optimized-two-vial-formulation-lipid-nanoemulsion-of-paclitaxel-for-targeted-delivery-to-tumor
#4
Lina Chen, Bingchen Chen, Li Deng, Baoan Gao, Yuansheng Zhang, Chan Wu, Nong Yu, Qinqin Zhou, Jianzhong Yao, Jianming Chen
The discovery of new intravenous drug delivery carrier for water-insoluble drug is a challenging task. In this paper, novel two-vial formulation of paclitaxel (PTX)-loaded lipid nanoemulsions (TPLEs) with particle sizes of 110nm (TPLE-1), 220nm (TPLE-2) and 380nm (TPLE-3), which were formed by mixing a PEG400 solution of PTX and 10% (w/w) blank lipid emulsions (BLEs) with different particle size prior to use, were developed and comparatively evaluated for their pharmaceutics, pharmacokinetics, biodistribution, in vitro and in vivo anticancer efficiency...
October 3, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28981321/foreword
#5
Susanne Cruickshank, Richard Henry
There is a significant body of evidence describing the benefits of using systemic anti-cancer therapy (SACT) agents, such as chemotherapy, biological, hormone and antibiotics, to treat people diagnosed with cancer (Cancer Research UK, 2017). However, the potential improvements in survival outcomes must be regularly weighed against the risk of adverse health effects associated with exposure to them. For patients, the risks are balanced against the need to treat the cancer. For health professionals, the risks simply result from the occupational exposure that can occur when caring for patients receiving these drugs...
September 6, 2017: British Journal of Nursing: BJN
https://www.readbyqxmd.com/read/28971759/steroidal-oximes-useful-compounds-with-antitumor-activities
#6
Catarina Canário, Samuel Silvestre, Amílcar Falcão, Gilberto Alves
BACKGROUND: Steroids play an important role in life because they can regulate a variety of biological processes and have been widely used in medicine namely as anti-inflammatory, anabolic, contraceptives and anticancer drugs. In recent years, there has been an increasing interest in the introduction of the oxime group in a large variety of molecules in order to increase their biological effects. This review highlights steroidal oximes with anticancer properties and their potential mechanisms of action, as well as data on their relative potencies reported in literature in the last few years...
October 3, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28971631/intravitreal-ziv-aflibercept-clinical-effects-and-economic-impact
#7
Sumit Randhir Singh, Avantika Dogra, Michael Stewart, Taraprasad Das, Jay Chhablani
During the past decade, drugs that inhibit the actions of vascular endothelial growth factor (VEGF) have become standard-of-care treatment for a variety of chorioretinal vascular conditions. The off-label, intravitreal use of ziv-aflibercept (Zaltrap) has provided clinicians with an additional cost-effective drug. The commercial preparation of ziv-aflibercept contains the same aflibercept (VEGF-trap) molecule as Eylea but has a much higher osmolarity (1000 mOsm/kg vs 300 mOsm/kg). Initial concerns regarding cytotoxicity and long-term safety of intravitreal ziv-aflibercept have been largely negated after a series of publications failed to identify adverse ocular and systemic side effects...
October 3, 2017: Asia-Pacific Journal of Ophthalmology
https://www.readbyqxmd.com/read/28970115/improved-oral-bioavailability-and-therapeutic-efficacy-of-erlotinib-through-molecular-complexation-with-phospholipid
#8
Chander Parkash Dora, Varun Kushwah, Sameer S Katiyar, Pradeep Kumar, Viness Pillay, Sarasija Suresh, Sanyog Jain
The current study was aimed to prepare a molecular complex of erlotinib (ERL) with phospholipid (PC) for enhancement of solubility and thus bioavailability, therapeutic efficacy and reducing the toxicity of erlotinib. Phospholipid complex of drug was prepared by solvent evaporation method and characterized by differential scanning calorimetry (DSC), Fourier transform infra-red spectroscopy (FT-IR), proton and phosphorus nuclear magnetic resonance spectroscopy ((1)H NMR and (31)P NMR), powder X-ray diffraction (P-XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM), which all explained the interactions of two components, validating the complexation phenomenon...
September 29, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28965478/an-in-vitro-assessment-of-novel-chitosan-bimetallic-ptau-nanocomposites-as-delivery-vehicles-for-doxorubicin
#9
Vareessh Maney, Moganavelli Singh
AIM: To synthesize and functionalize platinum (core)-gold (shell) bimetallic nanoparticles (PtAuBNps) with chitosan and doxorubicin to display favorable pharmacokinetics, biodegradability, biological activity and safety in vitro. MATERIALS & METHODS: PtAuBNps and their drug nanocomposites were morphologically and physico-chemically characterized. Binding studies determined the efficiency and stability of the platform. In vitro release kinetics were evaluated under simulated environments, cytotoxicity profiles through MTT and Sulforodhamine B assays and apoptosis induction using the dual EtBr/AO staining...
October 2, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28964764/the-sabre-trial-sirolimus-angioplasty-balloon-for%C3%A2-coronary-in-stent-restenosis-angiographic-results-and-1-year-clinical-outcomes
#10
Stefan Verheye, Mathias Vrolix, Indulis Kumsars, Andrejs Erglis, Dace Sondore, Pierfrancesco Agostoni, Kristoff Cornelis, Luc Janssens, Michael Maeng, Ton Slagboom, Giovanni Amoroso, Lisette Okkels Jensen, Juan F Granada, Pieter Stella
OBJECTIVES: The aim of this first-in-human study was to assess the safety and effectiveness of the Virtue sirolimus-eluting balloon in a cohort of patients with in-stent restenosis (ISR). BACKGROUND: Angioplasty balloons coated with the cytotoxic drug paclitaxel have been widely used for ISR treatment. The Virtue angioplasty balloon (Caliber Therapeutics, New Hope, Pennsylvania) delivers sirolimus in a nanoencapsulated liquid formulation. This clinical trial is the first to examine a sirolimus-eluting balloon for ISR...
September 19, 2017: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/28963991/synthesis-biological-evaluation-and-quantitative-structure-active-relationships-of-1-3-thiazolidin-4-one-derivatives-a-promising-chemical-scaffold-endowed-with-high-antifungal-potency-and-low-cytotoxicity
#11
Simone Carradori, Bruna Bizzarri, Melissa D'Ascenzio, Celeste De Monte, Rossella Grande, Daniela Rivanera, Alessanda Zicari, Emanuela Mari, Manuela Sabatino, Alexandros Patsilinakos, Rino Ragno, Daniela Secci
With reference to recent studies reporting on the various biological properties of the thiazolidinone scaffold, we synthesized more than a hundred compounds characterized by a 1,3-thiazolidin-4-one nucleus derivatised at the C2 with a hydrazine bridge linked to (cyclo)aliphatic or hetero(aryl) moieties, and their N-benzylated derivatives. These molecules were assayed as potential anti-Candida agents and they were shown to possess comparable, and in some cases higher biological activity than well-established topical and systemic antimycotic drugs (i...
September 19, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28963013/development-and-optimization-of-methotrexate-loaded-lipid-polymer-hybrid-nanoparticles-for-controlled-drug-delivery-applications
#12
Nayab Tahir, Asadullah Madni, Vimalkumar Balasubramanian, Mubashar Rehman, Alexandra Correia, Prince Muhammad Kashif, Ermei Mäkilä, Jarno Salonen, Hélder A Santos
Lipid-polymer hybrid nanoparticles (LPHNPs) are emerging platforms for drug delivery applications. In the present study, methotrexate loaded LPHNPs consisted of PLGA and Lipoid S100 were fabricated by employing a single-step modified nanoprecipitation method combined with self-assembly. A three factor, three level Box Behnken design using Design-Expert(®) software was employed to access the influence of three independent variables on the particle size, drug entrapment and percent drug release. The optimized formulation was selected through numeric optimization approach...
September 27, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28961040/genkwanin-nanosuspensions-a-novel-and-potential-antitumor-drug-in-breast-carcinoma-therapy
#13
Yijing Li, Jingyi Hong, Haowen Li, Xiaoyu Qi, Yifei Guo, Meihua Han, Xiangtao Wang
Recently, genkwanin (GKA) has been shown to display in vitro antitumor activity against some cancer cells, but its poor solubility restricted the in vivo study and further investigation of its antitumor therapeutic efficacy. In this paper, genkwanin nanosuspensions (GKA-NSps) were successfully prepared using D-alpha tocopherol acid polyethylene glycol succinate (TPGS) as a stabilizer using the precipitation-homogenization method. The obtained GKA-NSps had an average particle size of 183.1 ± 4.4 nm, a PDI value of 0...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28947244/novel-ph-responsive-supramolecular-hydrogels-of-chitosan-hydrochloride-and-polyoxometalate-in-vitro-in-vivo-and-preliminary-safety-evaluation
#14
Azizullah, Nisar-Ur-Rehman, Ali Haider, Ulrich Kortz, Saifullah Afridi, Muhammad Sohail, Sachin A Joshi, Jamshed Iqbal
In the current study, electrostatically-driven pH responsive, supramolecular hydrogels of the trilacunary Wells-Dawson-type 15-tungsto-2-phosphate polyanion (P2W15) and chitosan hydrochloride (ChCl) were prepared, using methacrylic acid as pH responsive agent using benzoyl peroxide (BPO) as initiator. The prepared hydrogels were characterized by FT-IR, SEM, XRD and thermal analyses (TGA-DSC). The swelling and pH based P2W15 release profile of the hydrogels showed maximum swellability and release at pH 7.4. Different mathematical models were applied, showing that P2W15 release followed supercase transport-II mechanism and zero-order kinetics...
September 22, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28945432/using-flash-nanoprecipitation-to-produce-highly-potent-and-stable-cellax-nanoparticles-from-amphiphilic-polymers-derived-from-carboxymethyl-cellulose-polyethylene-glycol-and-cabazitaxel
#15
Joseph Bteich, Simon A McManus, Mark J Ernsting, Mohammed Z Mohammed, Robert K Prud'homme, Kenneth K Sokoll
We report the use of Flash Nanoprecipitation (FNP) as an efficient and scalable means of producing Cellax nanoparticles. Cellax polymeric conjugates consisting of carboxymethyl cellulose functionalized with PEG and hydrophobic anticancer drugs, such as cabazitaxel (coined Cellax-CBZ), have been shown to have high potency against several oncology targets, including prostate cancer. FNP, a robust method used to create nanoparticles through rapid mixing, has been used to encapsulate several hydrophobic drugs with block co-polymer stabilizers, but has never been used to form nanoparticles from random copolymers, such as Cellax-CBZ...
September 25, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28932197/antiplasmodial-activity-and-toxicological-assessment-of-curcumin-plga-encapsulated-nanoparticles
#16
Zulaikha A Busari, Kabiru A Dauda, Olajumoke A Morenikeji, Funmilayo Afolayan, Oyetunde T Oyeyemi, Jairam Meena, Debasis Sahu, Amulya K Panda
Curcumin is a polyphenolic pigment isolated from the rhizomes of Curcuma longa (turmeric), a medicinal plant widely used in the ancient Indian and Chinese medicine. The antiplasmodial activity of curcumin is often hampered by its fast metabolism and poor water solubility, thus its incorporation into a delivery system could circumvent this problem. This study aimed to evaluate the in vivo antiplasmodial activity and the toxicity assessment of curcumin incorporated into poly (lactic-co-glycolic) acid (PLGA) nanoparticles...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28929244/analyzing-polymeric-matrix-for-fabrication-of-a-biodegradable-microneedle-array-to-enhance-transdermal-delivery
#17
Kuo-Yuan Hwa, Vincent H S Chang, Yao-Yi Cheng, Yue-Da Wang, Pey-Shynan Jan, Boopathi Subramani, Min-Ju Wu, Bo-Kai Wang
Traditional drug delivery systems, using invasive, transdermal, and oral routes, are limited by various factors, such as the digestive system environment, skin protection, and sensory nerve stimulation. To improve the drug delivery system, we fabricated a polysaccharide-based, dissolvable microneedle-based array, which combines the advantages of both invasive and transdermal delivery systems, and promises to be an innovative solution for minimally invasive drug delivery. In this study, we designed a reusable aluminum mold that greatly improved the efficiency and convenience of microneedle fabrication...
September 19, 2017: Biomedical Microdevices
https://www.readbyqxmd.com/read/28924201/discovery-semisynthesis-antiparasitic-and-cytotoxic-evaluation-of-14-membered-resorcylic-acid-lactones-and-their-derivatives
#18
Xue-Qing Zhang, Carmenza Spadafora, Laura M Pineda, Michelle G Ng, Ji-Hong Sun, Wei Wang, Chang-Yun Wang, Yu-Cheng Gu, Chang-Lun Shao
Ten antifouling 14-membered resorcylic acid lactones 1-10 were isolated previously with low or trace natural abundance from the zoanthid-derived Cochliobolus lunatus fungus. Further optimization of fermentation conditions led to the isolation of two major natural compounds 7 and 8 with multi-gram quantities. By one or two steps, we semisynthesized the six trace natural compounds 1-6 and a series of derivatives 11-27 of compounds 7 and 8 with high yields (65-95%). Compounds 11-13 showed strong antiplasmodial activity against Plasmodium falciparum with IC50 values of 1...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28921642/clinical-pharmacology-tools-and-evaluations-to-facilitate-comprehensive-dose-finding-in-oncology-a-continuous-risk-benefit-approach
#19
Julie M Bullock, Tiffany Lin, Sanela Bilic
Targeted therapies are now considered an integral component in the treatment armamentarium for many malignancies, and the approach to developing these drugs needs to be refined from the previous cytotoxic paradigm of toxicity-guided dose finding and identification of maximum tolerated dose to a paradigm driven by target activity. Moving away from the toxicity-driven dose finding and justification model requires an integrated approach in order to adequately characterize the risk-benefit of a drug. This approach starts with understanding the importance of collecting samples for pharmacokinetic and pharmacodynamic assessments in all phases of clinical development to fully characterize the pharmacokinetics and identify covariates and then correlating exposure to key markers of safety and efficacy in pharmacometric analyses to perform a robust risk-benefit assessment and establish the right dose...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28920712/maximized-nanodrug-loaded-mesenchymal-stem-cells-by-a-dual-drug-loaded-mode-for-the-systemic-treatment-of-metastatic-lung-cancer
#20
Sen Yao, Xuqian Li, Jingxuan Liu, Yuqing Sun, Zhuanhe Wang, Yanyan Jiang
Mesenchymal stem cells (MSCs), exhibiting tumor-tropic and migratory potential, can serve as cellular carriers to improve the effectiveness of anticancer agents. However, several challenges, such as the safety issue, the limited drug loading, the conservation of stemness and migration of MSCs, still remain in the MSC-based delivery system. In the present study, a novel nano-engineered MSC delivery system was established by loading doxorubicin (DOX)-polymer conjugates for the systemic treatment of pulmonary metastasis of breast cancer...
November 2017: Drug Delivery
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