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nanomedicine clinically relevant

Larissa Kotelevets, Eric Chastre, Didier Desmaële, Patrick Couvreur
Colorectal cancer is a wide-reaching health problem due to its incidence and to the high mortality rates. Adjuvant chemotherapies have considerably improved the prognosis and/or the overall survival of patients with locally advanced and metastatic cancers. Nevertheless, their efficiency remains limited due to intrinsic and emerging multidrug resistance (MDR) of cancer cells, and to major adverse effects and dose limiting toxicities. The present review discusses the knowledge of clinically relevant mechanisms of resistance to cytotoxic and targeted therapies for the treatment of colorectal cancer, and focuses on the benefit of nanomedicine approach to circumvent these processes...
November 30, 2016: International Journal of Pharmaceutics
Christopher F Adams, Andrew W Dickson, Jan-Herman Kuiper, Divya M Chari
Tissue engineering studies are witnessing a major paradigm shift to cell culture on biomimetic materials that replicate native tissue features from which the cells are derived. Few studies have been performed in this regard for neural cells, particularly in nanomedicine. For example, platforms such as magnetic nanoparticles (MNPs) have proven efficient as multifunctional tools for cell tracking and genetic engineering of neural transplant populations. However, as far as we are aware, all current studies have been conducted using neural cells propagated on non-neuromimetic substrates that fail to represent the mechano-elastic properties of brain and spinal cord microenvironments...
October 6, 2016: Nanoscale
Harivardhan Reddy Lakkireddy, Didier Bazile
The design of the first polymeric nanoparticles could be traced back to the 1970s, and has thereafter received considerable attention, as evidenced by the significant increase of articles and patents. This review article is an attempt to take advantage of the existing literature on the clinically tested and commercialized biodegradable PLA(G)A-PEG nanotechnology as a model to propose quality building and outline translation and development principles (quality by design) for polymeric nano-medicines. We built such an approach from various building blocks including material design, nano-assembly - i...
September 1, 2016: Advanced Drug Delivery Reviews
Christina von Roemeling, Wen Jiang, Charles K Chan, Irving L Weissman, Betty Y S Kim
Nanomedicine offers unique advantages in treating human cancers. However, physiological and pathological barriers within normal and disease tissues, which are highly variable among individuals, often hinder its effectiveness. The body possesses specific innate responses to nanoparticles (NPs), which when combined with unique pathophysiological signatures in the tumor microenvironment, can severely limit the utility of nanomedicine in the oncological setting. Furthermore, with the successes of cancer immunotherapies, understanding nanoimmune interactions and developing immune-smart cancer nanomedicine that can take advantage of the body's immune functions will increasingly become clinically relevant...
August 1, 2016: Trends in Biotechnology
Si-Ming Yu, Laura Gonzalez-Moragas, Maria Milla, Androniki Kolovou, Rachel Santarella-Mellwig, Yannick Schwab, Anna Laromaine, Anna Roig
UNLABELLED: Nanoparticles which surface adsorb proteins in an uncontrolled and non-reproducible manner will have limited uses as nanomedicinal products. A promising approach to avoid nanoparticle non-specific interactions with proteins is to design bio-hybrids by purposely pre-forming a protein corona around the inorganic cores. Here, we investigate, in vitro and in vivo, the newly acquired bio-identity of superparamagnetic iron oxide nanoparticles (SPIONs) upon their functionalization with a pre-formed and well-defined bovine serum albumin (BSA) corona...
October 1, 2016: Acta Biomaterialia
Yao Lu, Yuhua Wang, Lei Miao, Matthew Haynes, Guangya Xiang, Leaf Huang
Therapeutic anticancer vaccine development must address a number of barriers to achieve successful tumor specific killing, including effective antigen presentation and antigen-specific T-cell activation to mediate cytotoxic cellular effects, inhibition of an immune-suppressive tumor microenvironment in order to facilitate and enhance CTL activity, and induction of memory T-cells to prolong tumor rejection. While traditional as well as modern vaccines rely upon delivery of both antigen and adjuvant, a variety of clinically relevant cancers lack ideal immunogenic antigens...
August 28, 2016: Cancer Letters
Jennifer I Hare, Twan Lammers, Marianne B Ashford, Sanyogitta Puri, Gert Storm, Simon T Barry
Successfully translating anti-cancer nanomedicines from pre-clinical proof of concept to demonstration of therapeutic value in the clinic is challenging. Having made significant advances with drug delivery technologies, we must learn from other areas of oncology drug development, where patient stratification and target-driven design have improved patient outcomes. We should evolve our nanomedicine development strategies to build the patient and disease into the line of sight from the outset. The success of small molecule targeted therapies has been significantly improved by employing a specific decision-making framework, such as AstraZeneca's 5R principle: right target/efficacy, right tissue/exposure, right safety, right patient, and right commercial potential...
April 29, 2016: Advanced Drug Delivery Reviews
Mikhail O Durymanov, Alexey V Yarutkin, Dmitry V Bagrov, Dmitry V Klinov, Alexander V Kedrov, Nikolay K Chemeris, Andrey A Rosenkranz, Alexander S Sobolev
Low efficacy of cationic polymer-based formulations (polyplexes) for systemic gene delivery to tumors remains the crucial concern for their clinical translation. Here we show that modulating the physiological state of a tumor using clinically approved pharmaceuticals can improve delivery of intravenously injected polyplexes to murine melanoma tumors with different characteristics. Direct comparison of drugs with different mechanisms of action has shown that application of nitroglycerin or losartan improved extravasation and tumor uptake of polyplex nanoparticles, whereas angiotensin II had almost no effect on polyplex accumulation and microdistribution in the tumor tissue...
June 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Govind Soni, Khushwant S Yadav
Nanogels are being explored as drug delivery agents for targeting cancer due to their easy tailoring properties and ability to efficiently encapsulate therapeutics of diverse nature through simple mechanisms. Nanogels are proficiently internalized by the target cells, avoid accumulating in nontarget tissues thereby lower the therapeutic dosage and minimize harmful side effects. However, there is an urgent need for relevant clinical data from nanogels so as to allow translation of the nanogel concept into a viable therapeutic application for the treatment of cancer...
March 2016: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
Rumiana Koynova, Boris Tenchov
From their discovery half a century ago and the subsequent appreciation of their clinical utility, liposomes currently hold a recognized position in the mainstream of drug delivery systems. Conventional techniques for liposome preparation and size reduction are simple to implement and do not require sophisticated equipment. However, most of them are not easy to scale-up for industrial liposome production. With several liposomal formulations already on the market, and more in final clinical trials, the industrial scale production of liposomes has become reality, and so the range of liposome preparation methods has been extended by a number of techniques which are increasingly attractive, such as microfluidic hydrodynamic focusing, supercritical fluid processing, freeze-drying and spray-drying...
2015: Recent Patents on Nanotechnology
José das Neves, Rute Nunes, Francisca Rodrigues, Bruno Sarmento
Prevention plays an invaluable role in the fight against HIV/AIDS. The use of microbicides is considered an interesting potential approach for topical pre-exposure prophylaxis of HIV sexual transmission. The prospects of having an effective product available are expected to be fulfilled in the near future as driven by recent and forthcoming results of clinical trials. Different dosage forms and delivery strategies have been proposed and tested for multiple microbicide drug candidates presently at different stages of the development pipeline...
August 1, 2016: Advanced Drug Delivery Reviews
Daniela Arosio, Cesare Casagrande
The research of integrin-targeted anticancer agents has recorded important advancements in ingenious design of delivery systems, based either on the prodrug approach, or on nanoparticle carriers, but for now, none of these has reached a clinical stage of development. Past work in this area has been extensively reviewed by us and others. Thus, the purpose and scope of the present review is to survey the advancement reported in the last 3years, with focus on innovative delivery systems that appear to afford openings for future developments...
February 1, 2016: Advanced Drug Delivery Reviews
Amaya Nino-Pariente, Vicent J Nebot, Maria J Vicent
Herein, we present an overview on the current status of the characterization techniques and methodologies used to study the physicochemical descriptors that influence the final clinical performance of a given nanomedicine. The described techniques were selected based on their suitability to operate under relevant "native" conditions that mimic the physiological environment. Special emphasis is placed on those techniques that hold a greater potential to unravel dynamic, structural, and compositional features of soft organic nanomedicines relevant to the ability to bypass biological barriers, and hence allow for the rational design of drug delivery platforms with improved biological output...
2016: Current Pharmaceutical Design
Miles A Miller, Suresh Gadde, Christina Pfirschke, Camilla Engblom, Melissa M Sprachman, Rainer H Kohler, Katherine S Yang, Ashley M Laughney, Gregory Wojtkiewicz, Nazila Kamaly, Sushma Bhonagiri, Mikael J Pittet, Omid C Farokhzad, Ralph Weissleder
Therapeutic nanoparticles (TNPs) have shown heterogeneous responses in human clinical trials, raising questions of whether imaging should be used to identify patients with a higher likelihood of NP accumulation and thus therapeutic response. Despite extensive debate about the enhanced permeability and retention (EPR) effect in tumors, it is increasingly clear that EPR is extremely variable; yet, little experimental data exist to predict the clinical utility of EPR and its influence on TNP efficacy. We hypothesized that a 30-nm magnetic NP (MNP) in clinical use could predict colocalization of TNPs by magnetic resonance imaging (MRI)...
November 18, 2015: Science Translational Medicine
Nafiseh Nafissi, Marianna Foldvari
Neurotrophic factor genome engineering could have many potential applications not only in the deeper understanding of neurodegenerative disorders but also in improved therapeutics. The fields of nanomedicine, regenerative medicine, and gene/cell-based therapy have been revolutionized by the development of safer and efficient non-viral technologies for gene delivery and genome editing with modern techniques for insertion of the neurotrophic factors into clinically relevant cells for a more sustained pharmaceutical effect...
2015: Frontiers in Neuroscience
Rebekah Watkins, Ling Wu, Chenming Zhang, Richey M Davis, Bin Xu
Natural products have been used in medicine for many years. Many top-selling pharmaceuticals are natural compounds or their derivatives. These plant- or microorganism-derived compounds have shown potential as therapeutic agents against cancer, microbial infection, inflammation, and other disease conditions. However, their success in clinical trials has been less impressive, partly due to the compounds' low bioavailability. The incorporation of nanoparticles into a delivery system for natural products would be a major advance in the efforts to increase their therapeutic effects...
2015: International Journal of Nanomedicine
Andrew Owen, Steve Rannard
No abstract text is available yet for this article.
2015: Nanomedicine
Zhi-Qi Wang, Kai Liu, Zhi-Jun Huo, Xiao-Chen Li, Min Wang, Ping Liu, Bo Pang, Shi-Jiang Wang
BACKGROUND: Oral squamous cell carcinoma (OSCC) or cancers of oral cavity is one of the most common cancers worldwide with high rate of mortality and morbidity. At present, chemotherapy is one of the most effective treatments; however it often fails to meet the requirements in the clinical therapy. In the present study, we have successfully formulated ligand-decorated cancer-targeted CDDP-loaded PLGA-PEG/NR7 nanoparticles and demonstrated the feasibility of using NR7 peptide for targeted delivery, rapid intracellular uptake, and enhanced cytotoxic effect in receptor-overexpressed OSCC cancer cells...
2015: Journal of Nanobiotechnology
Jonas R Henriksen, Anncatrine L Petersen, Anders E Hansen, Christian G Frankær, Pernille Harris, Dennis R Elema, Annemarie T Kristensen, Andreas Kjær, Thomas L Andresen
Due to low ion permeability of lipid bilayers, it has been and still is common practice to use transporter molecules such as ionophores or lipophilic chelators to increase transmembrane diffusion rates and loading efficiencies of radionuclides into liposomes. Here, we report a novel and very simple method for loading the positron emitter (64)Cu(2+) into liposomes, which is important for in vivo positron emission tomography (PET) imaging. By this approach, copper is added to liposomes entrapping a chelator, which causes spontaneous diffusion of copper across the lipid bilayer where it is trapped...
October 21, 2015: ACS Applied Materials & Interfaces
Dab A Brill, J Andrew MacKay
Clinical pharmacokinetics (PK) primarily measures the concentration of drugs in the blood. For nanomedicines it may be more relevant to determine concentration within a target tissue. The emerging field of image-driven PK, which utilizes clinically accepted molecular imaging technology, empirically and noninvasively, measures concentration in multiple tissues. Image-driven PK represents the intersection of PK and biodistribution, combining to provide models of concentration across space and time. Image-driven PK can be used both as a research tool and in the clinic...
2015: Nanomedicine
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