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Ya Wen, Haiqing Dong, Kun Wang, Yan Li, Yongyong Li
Despite of inherent advantages over synthetic polymer based counterparts, protein nanoparticles remain unsatisfactory in fabrication owing to low size control, usage of toxic cross-linker or organic solvents. This partially contributes the marginal benefits of Abraxane® in clinic. Herein, a green synthetic, size controlled approach was developed to generate stable albumin nanoparticles. Physically packed ovalbumin (OVA) nanoclusters were temporally formed in heat, which was then used as the template to form protein nanoparticle chemically stabilized by intermolecular disulfide network...
March 6, 2018: ACS Applied Materials & Interfaces
Shuang Ding, Jian Xiong, Dan Lei, Xiao-Li Zhu, Hai-Jun Zhang
Breast cancer greatly threatens the health of women all over the word despite of several effective drugs. Targeted therapy for breast cancer is limited to human epidermal growth factor receptor 2 (HER2). Herceptin® , monoclonal antibody against HER2, is now widely used in HER2(+) breast cancer. Abraxane® , the current gold standard for paclitaxel (PTX) delivery, has shown superiority in breast cancer based on nanoparticle albumin bound technology. Despite these advances, further novel targeted therapy with more improved anti-tumor efficacy for breast cancer is still urgently needed...
2018: Journal of Cancer
Naomi Mizuta, Tsutomu Nakagawa, Kazuhiro Yamamoto, Tatsuya Nishioka, Manabu Kume, Hiroo Makimoto, Ikuko Yano, Hironobu Minami, Midori Hirai
Albumin-bound paclitaxel (Abraxane®, nab-paclitaxel) is not recommended to be administered concurrently or sequentially with other drugs due to concern for instability. The need to administer drugs separately increases infusion time. We evaluated the compatibility and stability of solutions containing nab-paclitaxel and other drugs, including gemcitabine hydrochloride, carboplatin, dexamethasone sodium phosphate, granisetron hydrochloride, and palonosetron hydrochloride. We visually examined changes in appearance, pH, and concentration of the mixed solutions of nab-paclitaxel and other drugs for up to 24 h...
July 20, 2017: Kobe Journal of Medical Sciences
Jacob E Shabason, Jerry Chen, Smith Apisarnthanarax, Nevena Damjanov, Bruce Giantonio, Arturo Loaiza-Bonilla, Peter J O'Dwyer, Mark O'Hara, Kim A Reiss, Ursina Teitelbaum, Paul Wissel, Jeffrey A Drebin, Charles Vollmer, Michael Kochman, Rosemarie Mick, Norge Vergara, Nirag Jhala, Abigail Doucette, John N Lukens, John P Plastaras, James M Metz, Edgar Ben-Josef
PURPOSE: Patients with locally advanced pancreatic cancer typically have poor outcomes, with a median survival of approximately 16 months. Novel methods to improve outcomes are needed. Nab-paclitaxel (Abraxane) has shown efficacy in pancreatic cancer and is FDA-approved for metastatic disease in combination with gemcitabine. Nab-paclitaxel is also a promising radiosensitizer based on laboratory studies, but it has never been clinically tested with definitive radiotherapy for locally advanced pancreatic carcinoma...
January 23, 2018: Cancer Chemotherapy and Pharmacology
Jian Xiong, Shuhua Han, Shuang Ding, Jingchao He, Haijun Zhang
Gastric cancer (GC) is the most lethal malignancy in the digestive system. This study investigated an antibody-nanoparticle conjugate (ANC) constructed with trastuzumab (Herceptin®) and nanoparticle albumin-bound paclitaxel (nab-paclitaxel, Abraxane®) (trastuzumab/nab‑paclitaxel) as a novel strategy of targeted therapy for human epidermal growth factor receptor 2 (HER2) positive GC. The ANC was fabricated with trastuzumab and nab‑paclitaxel by a 'one-step' synthesis using EDC/NHS. In vitro antitumor efficacy was evaluated by cell viability, apoptosis rate and cell cycle of HER2-positive GC NCI‑N87 cells and compared with paclitaxel (Taxol®), nab‑paclitaxel and trastuzumab/nab‑paclitaxel...
January 9, 2018: Oncology Reports
Luca Gianni, Mauro Mansutti, Antonio Anton, Lourdes Calvo, Giancarlo Bisagni, Begoña Bermejo, Vladimir Semiglazov, Marc Thill, Jose Ignacio Chacon, Arlene Chan, Serafin Morales, Isabel Alvarez, Arrate Plazaola, Milvia Zambetti, Andrew D Redfern, Christian Dittrich, Rebecca Alexandra Dent, Domenico Magazzù, Raffaella De Fato, Pinuccia Valagussa, Ignacio Tusquets
Importance: Studies of neoadjuvant chemotherapy regimens using anthracyclines followed by taxanes have reported a doubling of pathological complete remission (pCR) rates compared with anthracycline-based regimens alone. A reverse sequence did not reduce activity. Nab-paclitaxel is an albumin-bound nanoparticle of paclitaxel that allows for safe infusion without premedication, and its use led to a significantly higher rate of pCR in the GeparSepto trial. Objective: To determine whether nab-paclitaxel improves the outcomes of early and locally advanced human epidermal growth factor receptor 2 (ERBB2/HER2)-negative breast cancer compared with paclitaxel when delivered in a neoadjuvant setting...
January 11, 2018: JAMA Oncology
Sneha Gurudevan, Arul Prakash Francis, A Jayakrishnan
Amphotericin B (AmB), a hydrophobic drug with negligible aqueous solubility was conjugated to bovine serum albumin (BSA) via amide bond coupling to give 6 to 8 wt% drug payload. The resulting conjugate was characterized using SDS-PAGE and UV-visible, FTIR and CD spectroscopy. The conjugate was water-soluble to the extent of 150 mg/ml, was non-toxic to HEK 293 T cells at a concentration of 500 μg/ml (equivalent to ~30 μg AmB) and showed hemolysis of <5% at 200 μg/ml (equivalent to ~12 μg AmB) against human erythrocytes in vitro...
January 8, 2018: European Journal of Pharmaceutical Sciences
Aleksandra Adamska, Omar Elaskalani, Aikaterini Emmanouilidi, Minkyoung Kim, Norbaini Binti Abdol Razak, Pat Metharom, Marco Falasca
Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most chemoresistant cancers, and current therapies targeting cancer-associated molecular pathways have not given satisfactory results, owing in part to rapid upregulation of alternative compensatory pathways. Most of the available treatments are palliative, focussing on improving the quality of life. At present, available options are surgery, embolization, radiation, chemotherapy, immunotherapy and use of other more targeted drugs. In this review, we describe the cellular and molecular effects of current chemotherapy drugs such as gemcitabine, FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, irinotecan, and leucovorin) and ABRAXANE (nab-Paclitaxel), which have shown a survival benefit, although modest, for pancreatic cancer patients...
November 22, 2017: Advances in Biological Regulation
Guizhi Zhu, Geoffrey M Lynn, Orit Jacobson, Kai Chen, Yi Liu, Huimin Zhang, Ying Ma, Fuwu Zhang, Rui Tian, Qianqian Ni, Siyuan Cheng, Zhantong Wang, Nan Lu, Bryant C Yung, Zhe Wang, Lixin Lang, Xiao Fu, Albert Jin, Ido D Weiss, Harshad Vishwasrao, Gang Niu, Hari Shroff, Dennis M Klinman, Robert A Seder, Xiaoyuan Chen
Subunit vaccines have been investigated in over 1000 clinical trials of cancer immunotherapy, but have shown limited efficacy. Nanovaccines may improve efficacy but have rarely been clinically translated. By conjugating molecular vaccines with Evans blue (EB) into albumin-binding vaccines (AlbiVax), here we develop clinically promising albumin/AlbiVax nanocomplexes that self-assemble in vivo from AlbiVax and endogenous albumin for efficient vaccine delivery and potent cancer immunotherapy. PET pharmacoimaging, super-resolution microscopies, and flow cytometry reveal almost 100-fold more efficient co-delivery of CpG and antigens (Ags) to lymph nodes (LNs) by albumin/AlbiVax than benchmark incomplete Freund's adjuvant (IFA)...
December 5, 2017: Nature Communications
Li Liu, Qing Ye, Maggie Lu, Shih-Ta Chen, Hsiang-Wen Tseng, Ya-Chin Lo, Chien Ho
We have developed a new strategy to temporarily blunt the reticuloendothelial system uptake of nanodrugs, a major challenge for nanodrug delivery and causing off-target toxicities, using an FDA approved nutrition supplement, Intralipid. We have tested our methodology in rats using an experimental platinum-containing anti-cancer nanodrug and three FDA approved nanodrugs, Abraxane, Marqibo, and Onivyde, to determine their toxicities in liver, spleen, and kidney, with and without the addition of Intralipid. Our method illustrates its potentials to deliver nanodrugs with an increase in the bioavailability and a decrease in toxicities...
November 23, 2017: Scientific Reports
Hisashi Tsukada, Plamena Entcheva-Dimitrov, Armin Ernst, Samaan Rafeq, John H Keating, Kirk P Seward, Lonny Yarmus
BACKGROUND AND OBJECTIVE: Intratumoral administration of chemotherapeutic agents is a treatment modality that has proven efficacious in reducing the recurrence of tumours and increases specificity of treatment while minimizing systemic side effects. Direct intratumoral injection of malignant airway obstruction has potential therapeutic benefits but tissue drug concentrations and side-effect profiles are poorly understood. METHODS: Bronchial wall injection of generic paclitaxel (PTX) (102 injections of 0...
November 14, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
Qizhen Cao, Xinrui Yan, Kai Chen, Qian Huang, Marites P Melancon, Gabriel Lopez, Zhen Cheng, Chun Li
As a result of therapy-induced apoptosis, peripheral blood monocytes are recruited to tumors, where they become tumor-associated macrophages (TAMs). To date, few studies have investigated noninvasive molecular imaging for assessment of macrophage infiltration in response to therapy-induced apoptosis. Here, noninvasive assessment of changes in tumor accumulation of TAMs was proposed as a new way to measure early tumor response to anticancer therapy. Three different nanoparticles, QD710-Dendron quantum dots (QD710-D), Ferumoxytol, and PG-Gd-NIR813, were used for near-infrared fluorescence imaging, T2-weighted magnetic resonance imaging, and dual optical/T1-weighted MR imaging, respectively, in the MDA-MB-435 tumor model...
January 2018: Biomaterials
Fei-Fei An, Xiao-Hong Zhang
Biosafety is the primary concern in clinical translation of nanomedicine. As an intrinsic ingredient of human blood without immunogenicity and encouraged by its successful clinical application in Abraxane, albumin has been regarded as a promising material to produce nanoparticles for bioimaging and drug delivery. The strategies for synthesizing albumin-based nanoparticles could be generally categorized into five classes: template, nanocarrier, scaffold, stabilizer and albumin-polymer conjugate. This review introduces approaches utilizing albumin in the preparation of nanoparticles and thereby provides scientists with knowledge of goal-driven design on albumin-based nanomedicine...
2017: Theranostics
John T Butterfield, Hidong Kim, Daniel J Knauer, Wendy K Nevala, Svetomir N Markovic
Antibody directed chemotherapy (ADC) takes advantage of the selectivity of the monoclonal antibody to increase the efficacy of the chemotherapeutic agent, while reducing toxicity. Previously we described three nab-paclitaxel (Abraxane) nanoparticles coated with commercial monoclonal antibodies. Identifying the binding sites responsible for these particles could allow reverse engineering of nab-paclitaxel binding antibodies, creating a modular platform for antibody directed chemotherapeutic nanoparticles. Herein, Biacore surface plasmon resonance is used to identify an antibody binding site, HSA Peptide 40, on human serum albumin with nanomolar affinity for all three monoclonal antibodies...
November 3, 2017: Scientific Reports
Benedetta Pellegrino, Daniela Boggiani, Chiara Tommasi, Dante Palli, Antonino Musolino
Taxanes, including paclitaxel and docetaxel, are one of the most active cytotoxic agents in breast cancer  treatment  including  Her-2  positive  subtype characterized  by  aggressive  clinical  and pathological features since the early stage. However, their use is sometimes limited by the occurrence of hypersensivity reactions (HSRs) characterized by erythematous rashes, bronchospasm, respiratory distress, hypotension, and pulmonary edema. Cross-reactions between paclitaxel and docetaxel are described in literature with a rate ranging from 49% to 90%...
October 23, 2017: Acta Bio-medica: Atenei Parmensis
Feifan Xie, Elien De Thaye, An Vermeulen, Jan Van Bocxlaer, Pieter Colin
After being used for decades in clinical screening, dried blood spots (DBS) have recently received considerable attention for their application in pharmacokinetic and toxicokinetic studies in rodents. The goal of this study was to develop and apply a DBS-based assay for a pharmacokinetic study of paclitaxel (PTX) and its metabolites in SCID/Beige mice. A fast and sensitive UHPLC-MS/MS method has been developed for the simultaneous determination of PTX, its three metabolites (6α-hydroxy-paclitaxel, 3'-p-hydroxy-paclitaxel, and 6α,3'-p-dihydroxy-paclitaxel) and its stereoisomer 7-epi-paclitaxel...
October 18, 2017: Journal of Pharmaceutical and Biomedical Analysis
Feihu Wang, Michael Porter, Alexandros Konstantopoulos, Pengcheng Zhang, Honggang Cui
Paclitaxel (PTX) is one of the most successful drugs ever used in cancer chemotherapy, acting against a variety of cancer types. Formulating PTX with Cremophor EL and ethanol (Taxol®) realized its clinical potential, but the formulation falls short of expectations due to side effects such as peripheral neuropathy, hypotension, and hypersensitivity. Abraxane®, the albumin bound PTX, represents a superior replacement of Taxol® that mitigates the side effects associated with Cremophor EL. While Abraxane® is now considered a gold standard in chemotherapy, its 21% response rate leaves much room for further improvement...
December 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
Stephanie L Barnes, Anna G Sorace, Jennifer G Whisenant, J Oliver McIntyre, Hakmook Kang, Thomas E Yankeelov
This work evaluates quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted MRI (DW-MRI) parameters as early biomarkers of response in a preclinical model of triple negative breast cancer (TNBC). The standard Tofts' model of DCE-MRI returns estimates of the volume transfer constant (K(trans) ) and the extravascular extracellular volume fraction (ve ). DW-MRI returns estimates of the apparent diffusion coefficient (ADC). Mice (n = 38) were injected subcutaneously with MDA-MB-231...
September 15, 2017: NMR in Biomedicine
Di Wu, Mengjie Si, Hui-Yi Xue, Ho-Lun Wong
Breast cancer is the most common malignant disease in women worldwide, but the current drug therapy is far from optimal as indicated by the high death rate of breast cancer patients. Nanomedicine is a promising alternative for breast cancer treatment. Nanomedicine products such as Doxil(®) and Abraxane(®) have already been extensively used for breast cancer adjuvant therapy with favorable clinical outcomes. However, these products were originally designed for generic anticancer purpose and not specifically for breast cancer treatment...
2017: International Journal of Nanomedicine
Gulzar Ahmad, Rana El Sadda, Galina Botchkina, Iwao Ojima, James Egan, Mansoor Amiji
The main aim of this study was to evaluate the therapeutic efficacy of an oil-in-water nanoemulsion formulation encapsulating DHA-SBT-1214, a novel omega-3 fatty acid conjugated taxoid prodrug, against prostate cancer stem cells. Nanoemulsions of DHA-SBT-1214 (NE-DHA-SBT-1214) were prepared and characterized. In vitro delivery efficiency and cytotoxicity of NE-DHA-SBT-1214 was compared with solution formulation in PPT2 cells. In vivo studies included analysis of comparative efficacy of NE-DHA-SBT-1214 with Abraxane(®) and placebo nanoemulsions as well as post-treatment alternations in clonogenic and sphere-forming capabilities of the tumor cells...
October 10, 2017: Cancer Letters
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