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https://www.readbyqxmd.com/read/28501439/paclitaxel-what-has-been-done-and-the-challenges-remain-ahead
#1
REVIEW
Ezequiel Bernabeu, Maximiliano Cagel, Eduardo Lagomarsino, Marcela Moretton, Diego A Chiappetta
In recent years, the nanotechnology has offered researchers the opportunity to solve the problems caused by the vehicle of the standard and first formulation of paclitaxel (Taxol(®)), while maximizing the proven antineoplastic activity of the drug against many solid tumors. Hence, different types of nanocarriers have been employed to improve the efficacy, safety, physicochemical properties and pharmacokinetic/pharmacodynamic profile of this drug. To date, paclitaxel is the unique drug that is marketed in three different nanoplatforms for its parenteral delivery: polymeric nanoparticles (Abraxane(®)), liposomes (Lipusu(®)), and polymeric micelles (Genexol(®), Nanoxel(®) and Paclical(®))...
May 10, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28393881/tranilast-induced-stress-alleviation-in-solid-tumors-improves-the-efficacy-of-chemo-and-nanotherapeutics-in-a-size-independent-manner
#2
Panagiotis Papageorgis, Christiana Polydorou, Fotios Mpekris, Chrysovalantis Voutouri, Eliana Agathokleous, Constantina P Kapnissi-Christodoulou, Triantafyllos Stylianopoulos
Accumulation of mechanical stresses during cancer progression can induce blood and lymphatic vessel compression, creating hypo-perfusion, hypoxia and interstitial hypertension which decrease the efficacy of chemo- and nanotherapies. Stress alleviation treatment has been recently proposed to reduce mechanical stresses in order to decompress tumor vessels and improve perfusion and chemotherapy. However, it remains unclear if it improves the efficacy of nanomedicines, which present numerous advantages over traditional chemotherapeutic drugs...
April 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28381539/transient-tissue-priming-via-rock-inhibition-uncouples-pancreatic-cancer-progression-sensitivity-to-chemotherapy-and-metastasis
#3
Claire Vennin, Venessa T Chin, Sean C Warren, Morghan C Lucas, David Herrmann, Astrid Magenau, Pauline Melenec, Stacey N Walters, Gonzalo Del Monte-Nieto, James R W Conway, Max Nobis, Amr H Allam, Rachael A McCloy, Nicola Currey, Mark Pinese, Alice Boulghourjian, Anaiis Zaratzian, Arne A S Adam, Celine Heu, Adnan M Nagrial, Angela Chou, Angela Steinmann, Alison Drury, Danielle Froio, Marc Giry-Laterriere, Nathanial L E Harris, Tri Phan, Rohit Jain, Wolfgang Weninger, Ewan J McGhee, Renee Whan, Amber L Johns, Jaswinder S Samra, Lorraine Chantrill, Anthony J Gill, Maija Kohonen-Corish, Richard P Harvey, Andrew V Biankin, T R Jeffry Evans, Kurt I Anderson, Shane T Grey, Christopher J Ormandy, David Gallego-Ortega, Yingxiao Wang, Michael S Samuel, Owen J Sansom, Andrew Burgess, Thomas R Cox, Jennifer P Morton, Marina Pajic, Paul Timpson
The emerging standard of care for patients with inoperable pancreatic cancer is a combination of cytotoxic drugs gemcitabine and Abraxane, but patient response remains moderate. Pancreatic cancer development and metastasis occur in complex settings, with reciprocal feedback from microenvironmental cues influencing both disease progression and drug response. Little is known about how sequential dual targeting of tumor tissue tension and vasculature before chemotherapy can affect tumor response. We used intravital imaging to assess how transient manipulation of the tumor tissue, or "priming," using the pharmaceutical Rho kinase inhibitor Fasudil affects response to chemotherapy...
April 5, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28280335/nanoparticle-abraxane-possesses-impaired-proliferation-in-a549-cells-due-to-the-underexpression-of-glucosamine-6-phosphate-n-acetyltransferase-1-gnpnat1-gna1
#4
Minzhi Zhao, Haiyun Li, Yan Ma, He Gong, Shu Yang, Qiaojun Fang, Zhiyuan Hu
Abraxane (Abr), a US Food and Drug Administration-approved albumin-bound nanoparticle applied for the treatment of non-small-cell lung cancer, has been reported to be more effective than paclitaxel (PTX). To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. Only one protein, namely, glucosamine 6-phosphate N-acetyltransferase 1 (GNA1), showed significant differential expression (P<0...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28257998/the-battle-of-nano-paclitaxel
#5
REVIEW
Alexandros Marios Sofias, Michael Dunne, Gert Storm, Christine Allen
Paclitaxel (PTX) is one of the three most widely used chemotherapeutic agents, together with doxorubicin and cisplatin, and is first or second line treatment for several types of cancers. In 2000, Taxol, the conventional formulation of PTX, became the best selling cancer drug of all time with annual sales of 1.6 billion. In 2005, the introduction of the albumin-based formulation of PTX, known as Abraxane, ended Taxol's monopoly of the PTX market. Abraxane's ability to push the Taxol innovator and generic formulations aside attracted fierce competition amongst competitors worldwide to develop their own unique, new and improved formulation of PTX...
February 28, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28236692/synthesis-and-characterization-of-folate-decorated-albumin-bio-conjugate-nanoparticles-loaded-with-a-synthetic-curcumin-difluorinated-analogue
#6
Kaustubh A Gawde, Prashant Kesharwani, Samaresh Sau, Fazlul H Sarkar, Subhash Padhye, Sushil K Kashaw, Arun K Iyer
Albumin-bound paclitaxel colloidal nanoparticle (Abraxane®) is an FDA approved anticancer formulation available in the market. It is a suspension which is currently used therapeutically for treating cancers of the breast, lung, and pancreas among others. CDF is a novel new and potent synthetic curcumin analogue that is widely used for breast and ovarian cancer. The aim of this study was to use biocompatible albumin as well as folate decorated albumin to formulate colloidal nanoparticles encapsulating curcumin difluorinated (CDF)...
June 15, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28161480/multifunctionalized-iron-oxide-nanoparticles-for-selective-targeting-of-pancreatic-cancer-cells
#7
Sara Trabulo, Antonio Aires, Alexandra Aicher, Christopher Heeschen, Aitziber L Cortajarena
Nanomedicine nowadays offers novel solutions in cancer therapy by introducing multimodal treatments in one single formulation. In addition, nanoparticles act as nanocarriers changing the solubility, biodistribution and efficiency of the therapeutic molecules, thus generating more efficient treatments and reducing their side effects. To apply these novel therapeutic approaches, efforts are focused on the multi-functionalization of the nanoparticles and will open up new avenues to advanced combinational therapies...
February 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28108630/macropinocytosis-of-nab-paclitaxel-drives-macrophage-activation-in-pancreatic-cancer
#8
Jane Cullis, Despina Siolas, Antonina Avanzi, Sugata Barui, Anirban Maitra, Dafna Bar-Sagi
Pancreatic cancer is a devastating disease that is largely refractory to currently available treatment strategies. Therapeutic resistance is partially attributed to the dense stromal reaction of pancreatic ductal adenocarcinoma tumors that includes a pervasive infiltration of immunosuppressive (M2) macrophages. Nab-paclitaxel (trade name Abraxane) is a nanoparticle albumin-bound formulation of paclitaxel that, in combination with gemcitabine, is currently the first-line treatment for pancreatic cancer. Here, we show that macrophages internalized nab-paclitaxel via macropinocytosis...
January 20, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28069389/layer-by-layer-assembly-of-hierarchical-nanoarchitectures-to-enhance-the-systemic-performance-of-nanoparticle-albumin-bound-paclitaxel
#9
Hima Bindu Ruttala, Thiruganesh Ramasamy, Beom Soo Shin, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
Although protein-bound paclitaxel (PTX, Abraxane(®)) has been established as a standard PTX-based therapy against multiple cancers, its clinical success is limited by unfavorable pharmacokinetics, suboptimal biodistribution, and acute toxicities. In the present study, we aimed to apply the principles of a layer-by-layer (LbL) technique to improve the poor colloidal stability and pharmacokinetic pattern of nanoparticle albumin-bound paclitaxel (nab-PTX). LbL-based nab-PTX was successfully fabricated by the alternate deposition of polyarginine (pARG) and poly(ethylene glycol)-block-poly (L-aspartic acid) (PEG-b-PLD) onto an albumin conjugate...
March 15, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28049022/albumin-coated-nanocrystals-for-carrier-free-delivery-of-paclitaxel
#10
Joonyoung Park, Bo Sun, Yoon Yeo
Nanoparticles are used to deliver anticancer drugs to solid tumors. However, clinical development of nanoparticles is challenging because of their limitations in physicochemical properties, such as low drug loading efficiency and poor circulation stability. Low drug loading not only causes technical difficulty in administration but also increases the amount of co-delivered carrier materials, imposing biological burdens to patients. Poor circulation stability causes loss of pharmacokinetics benefits of nanoparticles...
December 31, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28042313/efficient-enhancement-of-blood-brain-barrier-permeability-using-acoustic-cluster-therapy-act
#11
Andreas K O Åslund, Sofie Snipstad, Andrew Healey, Svein Kvåle, Sverre H Torp, Per C Sontum, Catharina de Lange Davies, Annemieke van Wamel
The blood-brain barrier (BBB) is a major obstacle in drug delivery for diseases of the brain, and today there is no standardized route to surpass it. One technique to locally and transiently disrupt the BBB, is focused ultrasound in combination with gas-filled microbubbles. However, the microbubbles used are typically developed for ultrasound imaging, not BBB disruption. Here we describe efficient opening of the BBB using the promising novel Acoustic Cluster Therapy (ACT), that recently has been used in combination with Abraxane® to successfully treat subcutaneous tumors of human prostate adenocarcinoma in mice...
2017: Theranostics
https://www.readbyqxmd.com/read/27920893/antibody-drug-conjugates-and-other-nanomedicines-the-frontier-of-gynaecological-cancer-treatment
#12
REVIEW
David Howard, Jetzabel Garcia-Parra, Gareth D Healey, Cynthia Amakiri, Lavinia Margarit, Lewis W Francis, Deyarina Gonzalez, R Steven Conlan
Gynaecological cancers: malignancies of the cervix, uterus, ovaries, vagina and vulva, are responsible for over 1.1 million new cancer cases and almost half a million deaths annually. Ovarian cancer in particular is difficult to treat due to often being diagnosed at a late stage, and the incidence of uterine and vulvar malignancies are both on the rise. The field of nanomedicine is beginning to introduce drugs into the clinic for oncological applications exemplified by the liposomal drugs, Doxil and Myocet, the nanoparticle, Abraxane and antibody-drug conjugates (ADCs), Kadcyla and Adcetris...
December 6, 2016: Interface Focus
https://www.readbyqxmd.com/read/27873118/current-update-of-a-carboxymethylcellulose-peg-conjugate-platform-for-delivery-of-insoluble-cytotoxic-agents-to-tumors
#13
Yang Yang, Joseph Bteich, Shyh-Dar Li
Cytotoxic chemotherapeutic agents are used as the standard therapy for a range of significant cancers, but many of these drugs suffer from poor water solubility and low selectivity, limiting their clinical efficacy. To overcome these shortcomings, Cellax™ drug delivery platform was developed. Cellax™ is a polymer-based nanoparticle drug delivery system designed to solubilize hydrophobic drugs and target them to solid tumors, thereby enhancing the efficacy and reducing the side effects. Cellax-docetaxel (Cellax-DTX) displayed improved pharmacokinetic, safety, and efficacy profiles compared to native DTX (Taxotere®) and Nab-paclitaxel (Nab-PTX, Abraxane®) in multiple animal models...
March 2017: AAPS Journal
https://www.readbyqxmd.com/read/27748999/in-vitro-and-in-vivo-evaluation-of-pegylated-layer-by-layer-polyelectrolyte-coated-paclitaxel-nanocrystals
#14
Anna Polomska, Marc A Gauthier, Jean-Christophe Leroux
Drug nanocrystals (NCs) are colloidal dispersions composed almost entirely of drug. As such, there is substantial interest in targeting them to diseased tissues, where they can locally deliver high doses of the therapeutic. However, because of their uncontrolled dissolution characteristics in vivo and uptake by the monomolecular phagocyte system, achieving tumor accumulation is challenging. To address these issues, a layer-by-layer approach is adopted to coat paclitaxel NCs with alternating layers of oppositely charged polyelectrolytes, using a PEGylated copolymer as the top layer...
October 17, 2016: Small
https://www.readbyqxmd.com/read/27695347/clinical-comparative-investigation-of-efficacy-and-toxicity-of-cisplatin-plus-gemcitabine-or-plus-abraxane-as-first-line-chemotherapy-for-stage-iii-iv-non-small-cell-lung-cancer
#15
Dan Ai, Yan Guan, Xiu-Ju Liu, Chu-Feng Zhang, Peng Wang, Hong-Lu Liang, Qi-Sen Guo
PURPOSE: The purpose of this study was to observe the clinical efficacy and toxicity of cisplatin in combination with gemcitabine or Abraxane as first-line chemotherapy for stage III/IV non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 200 patients with advanced NSCLC, which was confirmed by pathology or cytology, were enrolled into our research by reviewing previous complete and retrievable medical records data of our hospital. A total of 100 patients were treated with gemcitabine (1,000 mg/m(2), day 1 and day 8) in combination with cisplatin (75 mg/m(2), days 1-3; GP group) and another 100 patients were treated with Abraxane (260 mg/m(2), day 1) in combination with cisplatin (75 mg/m(2), days 1-3; TP group)...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27632532/dce-mri-derived-parameters-in-evaluating-abraxane-induced-early-vascular-response-and-the-effectiveness-of-its-synergistic-interaction-with-cisplatin
#16
Xilin Sun, Lili Yang, Xuefeng Yan, Yingying Sun, Dongliang Zhao, Yang Ji, Kai Wang, Xiaoyuan Chen, Baozhong Shen
Our previous studies revealed molecular alterations of tumor vessels, varying from immature to mature alterations, resulting from Abraxane, and demonstrated that the integrin-specific PET tracer 18F-FPPRGD2 can be used to noninvasively monitor such changes. However, changes in the tumor vasculature at functional levels such as perfusion and permeability are also important for monitoring Abraxane treatment outcomes in patients with cancer. The purpose of this study is to further investigate the vascular response during Abraxane therapy and the effectiveness of its synergistic interaction with cisplatin using Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI)...
2016: PloS One
https://www.readbyqxmd.com/read/27487717/-a-case-of-a-corneal-disorder-after-breast-cancer-treatment-with-nab-paclitaxel
#17
Yuka Hosotani, Takanobu Morimatsu, Masashi Takata, Osamu Mimura
BACKGROUND: We report a case of a corneal disorder after breast cancer treatment with a microtubule inhibitor, nab-paclitaxel (Abraxane). CASE: A 55-year-old woman, who was referred to our clinic, presented with blurred vision. 2 weeks previously, she had been undergoing treatment with nab-paclitaxel, trastuzumab and pertuzumab. Visual acuity was 20/60 in right eye and 20/40 in left eye. Slit-lamp examination showed an atypical epithelium invasion of the cornea in both eyes and small epithelial defect in left eye...
June 2016: Nippon Ganka Gakkai Zasshi
https://www.readbyqxmd.com/read/27398441/paclitaxel-loaded-tpgs-b-pcl-nanoparticles-in-vitro-cytotoxicity-and-cellular-uptake-in-mcf-7-and-mda-mb-231-cells-versus-mpeg-b-pcl-nanoparticles-and-abraxane%C3%A2
#18
COMPARATIVE STUDY
Ezequiel Bernabeu, Lorena Gonzalez, Maria J Legaspi, Marcela A Moretton, Diego A Chiappetta
Nanomedicines have become an attractive platform for the development of novel drug delivery systems in cancer chemotherapy. Polymeric nanoparticles (NPs) represent one of the best well-investigated nanosized carriers for delivery of antineoplastic compounds. The "Pegylation strategy" of drug delivery systems has been used in order to improve carrier biodistribution, however, some nanosized systems with PEG on their surface have exhibited poorly-cellular drug internalization. In this context, the purpose of the present study was to compare in vitro performance of two paclitaxel (PTX)-loaded NPs systems based on two biocompatible copolymers of alpha tocopheryl polyethylene glycol 1000 succinate-block-poly(ε-caprolactone) (TPGS-b-PCL) and methoxyPEG- block-poly(ε-caprolactone) (mPEG-b-PCL) in terms of citotoxicity and PTX cellular uptake...
January 2016: Journal of Nanoscience and Nanotechnology
https://www.readbyqxmd.com/read/27359113/a-platform-for-rapid-quantitative-assessment-of-multiple-drug-combinations-simultaneously-in-solid-tumors-in-vivo
#19
Joyoti Dey, William S Kerwin, Marc O Grenley, Joseph R Casalini, Ilona Tretyak, Sally H Ditzler, Derek J Thirstrup, Jason P Frazier, Daniel W Pierce, Michael Carleton, Richard A Klinghoffer
While advances in high-throughput screening have resulted in increased ability to identify synergistic anti-cancer drug combinations, validation of drug synergy in the in vivo setting and prioritization of combinations for clinical development remain low-throughput and resource intensive. Furthermore, there is currently no viable method for prospectively assessing drug synergy directly in human patients in order to potentially tailor therapies. To address these issues we have employed the previously described CIVO platform and developed a quantitative approach for investigating multiple combination hypotheses simultaneously in single living tumors...
2016: PloS One
https://www.readbyqxmd.com/read/27297780/acoustic-cluster-therapy-act-enhances-the-therapeutic-efficacy-of-paclitaxel-and-abraxane%C3%A2-for-treatment-of-human-prostate-adenocarcinoma-in-mice
#20
Annemieke van Wamel, Per Christian Sontum, Andrew Healey, Svein Kvåle, Nigel Bush, Jeffrey Bamber, Catharina de Lange Davies
Acoustic cluster therapy (ACT) is a novel approach for ultrasound mediated, targeted drug delivery. In the current study, we have investigated ACT in combination with paclitaxel and Abraxane® for treatment of a subcutaneous human prostate adenocarcinoma (PC3) in mice. In combination with paclitaxel (12mg/kg given i.p.), ACT induced a strong increase in therapeutic efficacy; 120days after study start, 42% of the animals were in stable, complete remission vs. 0% for the paclitaxel only group and the median survival was increased by 86%...
August 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
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