The Experts below are selected from a list of 13092 Experts worldwide ranked by ideXlab platform
Jie Kong - One of the best experts on this subject based on the ideXlab platform.
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amphiphilic polymer drug Conjugates based on acid sensitive 100 hyperbranched polyacetals for cancer therapy
Journal of Materials Science, 2017Co-Authors: Xiao Dua, Heng Che, Sha Zhang, Jie KongAbstract:A new type of acid-sensitive 100% hyperbranched polyacetals (HBPA) was synthesized, which could be completely degraded into small molecules under acidic environment and avoid the accumulative toxicity in vivo. The AB2 monomer was synthesized by 4-carboxybenzaldehyde and 2-bromoethanol. The bulk polycondensation was carried out in vacuum environment to remove water byproduct. The massive terminal aldehyde groups of HBPA were conjugated with mPEG-NH2 and doxorubicins to form amphiphilic acid-sensitive polymer–drug Conjugates (DOX-HBPA-PEG). The stability of the micelles of DOX-HBPA-PEG was evaluated by DLS at different pH value in phosphate buffer saline (PBS). The DOX release in vitro showed that the cumulative release rate was 14.51% in pH 7.4 PBS after 24 h and the cumulative release rate was 48.56% in pH 6.0 PBS after 24 h. The results of cell viability of DOX-HBPA-PEG and HBPA-PEG showed that the polymer–DOX Conjugates were effective drug delivery systems. The uptake process of DOX-HBPA-PEG by A549 cells showed that the micelle was totally swallowed in 1 h later. The controllable drug release nature, stability, biocompatibility and completely degradable structures (acid-sensitive) make them to be promising drug delivery systems.
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Amphiphilic polymer–drug Conjugates based on acid-sensitive 100% hyperbranched polyacetals for cancer therapy
Journal of Materials Science, 2017Co-Authors: Xiao Duan, Shan Zhang, Heng Chen, Jie KongAbstract:A new type of acid-sensitive 100% hyperbranched polyacetals (HBPA) was synthesized, which could be completely degraded into small molecules under acidic environment and avoid the accumulative toxicity in vivo. The AB2 monomer was synthesized by 4-carboxybenzaldehyde and 2-bromoethanol. The bulk polycondensation was carried out in vacuum environment to remove water byproduct. The massive terminal aldehyde groups of HBPA were conjugated with mPEG-NH2 and doxorubicins to form amphiphilic acid-sensitive polymer–drug Conjugates (DOX-HBPA-PEG). The stability of the micelles of DOX-HBPA-PEG was evaluated by DLS at different pH value in phosphate buffer saline (PBS). The DOX release in vitro showed that the cumulative release rate was 14.51% in pH 7.4 PBS after 24 h and the cumulative release rate was 48.56% in pH 6.0 PBS after 24 h. The results of cell viability of DOX-HBPA-PEG and HBPA-PEG showed that the polymer–DOX Conjugates were effective drug delivery systems. The uptake process of DOX-HBPA-PEG by A549 cells showed that the micelle was totally swallowed in 1 h later. The controllable drug release nature, stability, biocompatibility and completely degradable structures (acid-sensitive) make them to be promising drug delivery systems.
María J. Vicent - One of the best experts on this subject based on the ideXlab platform.
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Smart branched polymer drug Conjugates as nano-sized drug delivery systems
Biomaterials science, 2015Co-Authors: Aroa Duro-castano, Julie Movellan, María J. VicentAbstract:Polymer–drug Conjugates represent excellent nanopharmaceutical candidates, as they offer multiple advantages related to their intrinsic characteristics. Many of the said characteristics are provided by the covalent bonding between the drug and the polymer. However, their clinical development has been slow and only one polymer–drug conjugate has reached the market, thus there remains an urgent need for the development of new and smart polymeric systems. Desirable characteristics of these new systems include higher molecular weight and degree of homogeneity, predictable conformations in solution, multivalency, and increased drug loading capacity, amongst others. With these aims in mind, branched polymers are ideal candidates due to their unique rheological, mechanical, and biomedical properties derived from their structure, inaccessible for linear polymers. Within this review, the synthetic strategies developed and the main efforts towards branched polymer implementation as carriers for polymer–drug Conjugates will be addressed.
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Polymer--drug Conjugates as nano-sized medicines.
Current opinion in biotechnology, 2011Co-Authors: Fabiana Canal, Joaquin Sanchis, María J. VicentAbstract:Polymer Therapeutics have enormously evolved in the past decades. Several polymeric drugs as well as polymer–protein Conjugates have been in the market since the 90s, but although polymer–drug Conjugates are already in clinical trials they still need to reach this final goal. There are four main convergent strategies to move this platform technology further. First, exploitation of new molecular targets in cancer therapy and design of polymer–drug Conjugates as treatments for other diseases. Second, the development of combination therapy. Third, attempts to improve polymer chemistry, including the use of new well-defined architectures and the optimization of the advanced characterization techniques essential to transform a promising conjugate into a candidate for clinical evaluation. Finally, increased understanding of polymer conjugate features that govern clinical risk–benefit is leading to an appreciation of clinical biomarkers that will open new possibilities for personalized therapy.
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Polymer–drug Conjugates for novel molecular targets
Nanomedicine (London England), 2010Co-Authors: Joaquin Sanchis, Fabiana Canal, Rut Lucas, María J. VicentAbstract:Polymer therapeutics can be already considered as a promising field in the human healthcare context. The discovery of the enhanced permeability and retention effect by Maeda, together with the modular model for the Polymer-Drug conjugate proposed by Ringsdorf, directed the early steps of polymer therapeutics towards cancer therapy. Orthodox anticancer drugs were preferentially chosen in the development of the first Conjugates. The fast evolution of polymer chemistry and bioconjugation techniques, and a deeper understanding of cell biology has opened up exciting new challenges and opportunities. Four main directions have to be considered to develop this 'platform technology' further: the control of the synthetic process, the exhaustive characterization of the conjugate architectures, the conquest of combination therapy and the disclosure of new therapeutic targets. We illustrate in this article the exciting approaches offered by Polymer-Drug Conjugates beyond classical cancer therapy, focusing on new, more effective and selective targets in cancer and in their use as treatments for other major human diseases.
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combination therapy opportunities and challenges for polymer drug Conjugates as anticancer nanomedicines
Advanced Drug Delivery Reviews, 2009Co-Authors: Francesca Greco, María J. VicentAbstract:The discovery of new molecular targets and the subsequent development of novel anticancer agents are opening new possibilities for drug combination therapy as anticancer treatment. Polymer-Drug Conjugates are well established for the delivery of a single therapeutic agent, but only in very recent years their use has been extended to the delivery of multi-agent therapy. These early studies revealed the therapeutic potential of this application but raised new challenges (namely, drug loading and drugs ratio, characterisation, and development of suitable carriers) that need to be addressed for a successful optimisation of the system towards clinical applications.
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Polymer-Drug Conjugates: current status and future trends.
Frontiers in bioscience : a journal and virtual library, 2008Co-Authors: Francesca Greco, María J. VicentAbstract:Polymer Conjugates are nano-sized, multi-component constructs already in the clinic as anticancer compounds, both as single agents or as elements of combinations. They have the potential to improve pharmacological therapy of a variety of solid tumors. Polymer-Drug conjugation promotes passive tumor targeting by the enhanced permeability and retention (EPR) effect and allows for lysosomotropic drug delivery following endocytic capture. In the first part of this review, we analyze the promising results arising from clinical trials of polymer-bound chemotherapy. The experience gained on these studies provides the basis for the development of a more sophisticated second-generation of polymer Conjugates. However, many challenges still lay ahead providing scope to develop and refine this field. The ''technology platform'' of polymer therapeutics allows the development of both new and exciting polymeric materials, the incorporation of novel bioactive agents and combinations thereof to address recent advances in drug therapy. The rational design of polymer drug Conjugates is expected to realize the true potential of these "nanomedicines".
Xin Pang - One of the best experts on this subject based on the ideXlab platform.
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ph responsive polymer drug Conjugates design and progress
Journal of Controlled Release, 2016Co-Authors: Xin Pang, Yue Jiang, Qicai Xiao, Albert Wingnang Leung, Heyu HuaAbstract:Abstract Polymer–drug Conjugates are becoming established as a shining platform for drug delivery. Incorporation of pH-responsive linker between drug and polymer is expected to realize triggered release of bioactive agents from Conjugates in specific sites, either in mildly acidic extracellular matrices of tumor tissues or, after cellular internalization, in acidic endosomes and lysosomes. As an emerging drug delivery system, such pH-responsive polymer–drug Conjugates are able to selectively deliver and activate drug molecules while reducing their systemic side-effects. In this review, we present the recent advances in pH-responsive polymer–drug Conjugates with different chemical structures and architectures, and attempt to clarify their mechanism of action, synthesis and characterization technology. Furthermore, several promising approaches for the future will also be suggested.
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Polymer-Drug Conjugates: recent progress on administration routes
Expert opinion on drug delivery, 2014Co-Authors: Xin Pang, Xiaoye Yang, Guangxi ZhaiAbstract:Introduction: Polymer-Drug Conjugates are an important part of polymer therapeutics. Recently, they have been used as an appealing platform for drug delivery. As a delivery vector, the route of administration performs a serious impact on the accessibility of drug molecules to their respective target site and therapeutic index. Furthermore, the physicochemical and biological properties of Conjugates also correlate distinctly with the route of administration.Areas covered: This article reviews the recent advances of Polymer-Drug Conjugates as drug delivery systems through parenteral, enteral and topical routes. In particular, it mainly focuses on the classical and emerging routes such as injection, oral, transdermal, pulmonary and ocular routes using Polymer-Drug Conjugates as delivery systems.Expert opinion: Although polymer-conjugated drug delivery systems reported so far face severe shortcoming of being incomplete methodology and limited routes for administration (mostly concentrated in injection), some ...
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Polymer–drug Conjugates: present state of play and future perspectives
Drug Discovery Today, 2013Co-Authors: Xin Pang, Haiqun Zhang, Ying-jie Zhai, Guangxi ZhaiAbstract:Polymer conjugation is an efficient approach to improve therapeutic properties of drugs and biological agents. Since the first synthetic polymer–drug conjugate entered clinical trials in 1994, this technology has undergone notable development for the introduction and study of novel polymers and for the progress in the biological rationale for designing Conjugates. Not surprisingly, new polymers, in addition to the best known polyethylene glycol, poly[N-(2-hydroxypropyl)methacrylamide], are continuously conjugated with drugs to achieve biodegradable, stimuli-sensitive and targeted systems in an attempt to prolong blood circulation times and enhance drug concentrations at the intended site of action. This overview focuses on bioConjugates of water-soluble polymers with low molecular weight drugs. Additionally, the most recent achievements in the polymer–drug conjugate field and several promising approaches for the future are discussed.
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Polymer-Drug Conjugates: present state of play and future perspectives.
Drug discovery today, 2013Co-Authors: Xin Pang, Haiqun Zhang, Ying-jie Zhai, Guangxi ZhaiAbstract:Polymer conjugation is an efficient approach to improve therapeutic properties of drugs and biological agents. Since the first synthetic Polymer-Drug conjugate entered clinical trials in 1994, this technology has undergone notable development for the introduction and study of novel polymers and for the progress in the biological rationale for designing Conjugates. Not surprisingly, new polymers, in addition to the best known polyethylene glycol, poly[N-(2-hydroxypropyl)methacrylamide], are continuously conjugated with drugs to achieve biodegradable, stimuli-sensitive and targeted systems in an attempt to prolong blood circulation times and enhance drug concentrations at the intended site of action. This overview focuses on bioConjugates of water-soluble polymers with low molecular weight drugs. Additionally, the most recent achievements in the Polymer-Drug conjugate field and several promising approaches for the future are discussed.
Francesca Greco - One of the best experts on this subject based on the ideXlab platform.
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Feasibility of Polymer-Drug Conjugates for non-cancer applications
Current Opinion in Colloid & Interface Science, 2017Co-Authors: Az Alddien Natfji, Helen M. I. Osborn, Francesca GrecoAbstract:Abstract Polymer-Drug Conjugates have been intensely studied in the context of improving cancer chemotherapy and yet the only Polymer-Drug conjugate on the market (Movantik®) has a different therapeutic application (relieving opioid-induced constipation). In parallel, a number of studies have recently been published proposing the use of this approach for treating diseases other than cancer. In this commentary, we analyse the many and very diverse applications that have been proposed for Polymer-Drug Conjugates (ranging from inflammation to cardiovascular diseases) and the rationales underpinning them. We also highlight key design features to be considered when applying Polymer-Drug Conjugates to these new therapeutic areas.
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Impact of the Enhanced Permeability and Retention (EPR) Effect and Cathepsins Levels on the Activity of Polymer-Drug Conjugates
Polymers, 2014Co-Authors: Amit Kumar Rajora, Helen M. I. Osborn, Divyashree Ravishankar, Francesca GrecoAbstract:Polymer-Drug Conjugates have demonstrated clinical potential in the context of anticancer therapy. However, such promising results have, to date, failed to translate into a marketed product. Polymer-Drug Conjugates rely on two factors for activity: (i) the presence of a defective vasculature, for passive accumulation of this technology into the tumour tissue (enhanced permeability and retention (EPR) effect) and (ii) the presence of a specific trigger at the tumour site, for selective drug release (e.g., the enzyme cathepsin B). Here, we retrospectively analyse literature data to investigate which tumour types have proved more responsive to Polymer-Drug Conjugates and to determine correlations between the magnitude of the EPR effect and/or expression of cathepsin B. Lung, breast and ovarian cancers showed the highest response rate (30%, 47% and 41%, respectively for cathepsin-activated Conjugates and 31%, 43%, 40%, across all Conjugates). An analysis of literature data on cathepsin content in various tumour types showed that these tumour types had high cathepsin content (up to 3835 ng/mg for lung cancer), although marked heterogeneity was observed across different studies. In addition, these tumour types were also reported as having a high EPR effect. Our results suggest that a pre-screening of patient population could bring a more marked clinical benefit.
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Engineering Polymer Systems for Improved Drug Delivery - Polymer-Drug Conjugates
Fundamentals of Pharmaceutical Nanoscience, 2013Co-Authors: Cristina Fante, Francesca GrecoAbstract:Polymer-Drug Conjugates are nanosized drug delivery systems, which comprise several drug molecules covalently attached to a polymeric carrier. This chapter provides an overview of this technology in the context of drug delivery. Particular emphasis is given to different approaches and techniques used to synthesise and characterise Polymer-Drug Conjugates. In the final part of the chapter current applications of this technology are also discussed.
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combination therapy opportunities and challenges for polymer drug Conjugates as anticancer nanomedicines
Advanced Drug Delivery Reviews, 2009Co-Authors: Francesca Greco, María J. VicentAbstract:The discovery of new molecular targets and the subsequent development of novel anticancer agents are opening new possibilities for drug combination therapy as anticancer treatment. Polymer-Drug Conjugates are well established for the delivery of a single therapeutic agent, but only in very recent years their use has been extended to the delivery of multi-agent therapy. These early studies revealed the therapeutic potential of this application but raised new challenges (namely, drug loading and drugs ratio, characterisation, and development of suitable carriers) that need to be addressed for a successful optimisation of the system towards clinical applications.
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Polymer−Drug Conjugates for Combination Anticancer Therapy: Investigating the Mechanism of Action
Journal of medicinal chemistry, 2009Co-Authors: Gianfranco Pasut, Francesca Greco, Cristina Fante, Anna Mero, Raniero Mendichi, Rebecca J. Green, Francesco M. VeroneseAbstract:We developed a family of Polymer-Drug Conjugates carrying the combination of the anticancer agent epirubicin (EPI) and nitric oxide (NO). EPI-PEG-(NO)8, carrying the highest content of NO, displayed greater activity in Caco-2 cells while it decreased toxicity against endothelium cells and cardiomyocytes with respect to free EPI. FACS and confocal microscopy confirmed Conjugates internalization. Light scattering showed formation of micelle whose size correlated with internalization rate. EPI-PEG-(NO)8 showed increased bioavailability in mice compared to free EPI.
Heyu Hua - One of the best experts on this subject based on the ideXlab platform.
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ph responsive polymer drug Conjugates design and progress
Journal of Controlled Release, 2016Co-Authors: Xin Pang, Yue Jiang, Qicai Xiao, Albert Wingnang Leung, Heyu HuaAbstract:Abstract Polymer–drug Conjugates are becoming established as a shining platform for drug delivery. Incorporation of pH-responsive linker between drug and polymer is expected to realize triggered release of bioactive agents from Conjugates in specific sites, either in mildly acidic extracellular matrices of tumor tissues or, after cellular internalization, in acidic endosomes and lysosomes. As an emerging drug delivery system, such pH-responsive polymer–drug Conjugates are able to selectively deliver and activate drug molecules while reducing their systemic side-effects. In this review, we present the recent advances in pH-responsive polymer–drug Conjugates with different chemical structures and architectures, and attempt to clarify their mechanism of action, synthesis and characterization technology. Furthermore, several promising approaches for the future will also be suggested.