[PDF] Nanocarriers For The Delivery Of Combination Drugs eBook
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Nanocarriers for the Delivery of Combination Drugs focuses on the role of nanocarriers in the delivery of combination drugs for the management and treatment of various diseases. Nanocarriers belonging to the category of polymeric nanoparticles, dendrimers, lipidic nanocarriers (like nanoemulsions), liposomes, solid lipid nanoparticles, nanostructured lipid carriers are now being used in the drug delivery of combination drugs. This book helps readers assimilate all the information available surrounding the application of various nanocarrier technologies for the delivery of combination drugs of synthetic and natural origin, including small and large molecules. This is an important reference source for pharmaceutical scientists and biomaterials scientists who are looking to gain an increased understanding on how nanotechnology is improving the efficiency of combination drug delivery. Outlines how nanocarriers are used to enhance combination drug delivery systems Assesses the major challenges of delivering combination drugs successfully, and explains how nanocarriers can help meet these challenges Explores the characteristics of a variety of nanocarrier material types
Author : Alexandru Mihai Grumezescu Publisher : William Andrew Page : 580 pages File Size : 35,99 MB Release : 2019-03-14 Category : Medical ISBN : 0128166290
Nanomaterials for Drug Delivery and Therapy presents recent advances in the field of nanobiomaterials and their important applications in drug delivery, therapy and engineering. The book offers pharmaceutical perspectives, exploring the development of nanobiomaterials and their interaction with the human body. Chapters show how nanomaterials are used in treatments, including neurology, dentistry and cancer therapy. Authored by a range of contributors from global institutions, this book offers a broad, international perspective on how nanotechnology-based advances are leading to novel drug delivery and treatment solutions. It is a valuable research resource that will help both practicing medics and researchers in pharmaceutical science and nanomedicine learn more on how nanotechnology is improving treatments. Assesses the opportunities and challenges of nanotechnology-based drug delivery systems Explores how nanotechnology is being used to create more efficient drug delivery systems Discusses which nanomaterials make the best drug carriers
Combination therapy is preferred over monotherapy to treat cancer as it can show better therapeutic outcomes and also delay the onset of resistance by targeting multiple cell-survival pathways in cancer cells. Rationally developed combinations with monoclonal antibodies and small molecule drugs in the form of antibody-drug conjugates or antibody nanoparticle conjugates allow us to take advantage of the cellular targeting of the potent cytotoxic agents, thereby widening the scope for dose reduction while maintaining the required therapeutic response. This can in turn improve patient tolerability by reducing the off target toxicities. For the therapy of ErbB2 positive breast cancer, the monoclonal antibody, Trastuzumab, is the FDA approved therapy. The receptor tyrosine kinase, ErbB2 is a viable target in 20-25 % breast cancer patients due to its overexpression. Its degradation is associated with slower progression of the disease and increased survival times. While the monoclonal antibody Trastuzumab (HerceptinTM) is the first line therapy in such patients, monotherapy with Trastuzumab has shown little benefit and therefore must be given with chemotherapeutic agents. Such combinations also help in delaying the development of resistance to Trastuzumab, since multiple cellular pathways can be targeted simultaneously. ErbB2 is a client protein of heat shock protein 90 and 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) is a potent inhibitor of HSP90. Previous work in our lab has demonstrated strong synergy of action between 17-AAG and a model cytotoxic agent doxorubicin. In order to further improve the efficacy of the therapy, our goal was to replace doxorubicin with a more potent, clinically relevant agent paclitaxel (PTX), which has been shown to have strong synergistic antitumor effect with 17-AAG in ErbB2-driven breast cancers. Since synergy of such therapy is often sequence and dose ratio specific, co-delivery of the drugs via the same vehicle is desirable as well as beneficial. For this purpose, polymeric micelles prepared from a biodegradable block copolymer were chose. Polypeptides have an inherent property to assemble into supramolecular structures in solution. The formation of supramolecular structures is a controlled and organized process that depends by and large on the nature of the polypeptide and conditions of the solvent it is exposed to. Formation of amphiphilic copolymers based on such polypeptides can allow for tailoring the assembly process to a predefined nanoscale supramolecular structure, which can then be used as drug delivery vehicles. The overall process of self-assembly of such amphiphilic copolymers can then be regarded as a complex phenomenon of structural organization that is governed by the nature of constituent hydrophilic and hydrophobic blocks, their relative lengths, as well as properties of the solvent-phobic block that is the driving force for self-assembly. The inherent biocompatibility and biodegradability of polypeptides is of additional advantage for their biological applications. For the purpose of the current study, amphiphilic block copolymer with following composition was chosen: polyethylene glycol (PEG) as the hydrophilic, stealth imparting block and polyleucine (PLeu) as the hydrophobic part and the initiator of micelle formation in aqueous environment. The variables explored in the current study were altering the ratio of lengths of constituent blocks as well as chirality of PLeu block and the temperature of solvent used for preparation of micelles via the film rehydration method. The impact of all these variables on the thermodynamic stability as well as type of secondary structures formed and the influence of these attributes on the ability of the micelles to encapsulate a combination of hydrophobic drugs into their core are also described. Dual drug-loaded micelles thus prepared could load 17-AAG and PTX in a ratio 2:1 by weight. The formulation showed a high level of synergy on BT-474 cells that express a high amount of ErbB2 while the synergy was negligible in ErbB2low MCF-7 cells. The strong synergy also observed when the formulation was tested in an orthotopic breast cancer mouse model developed using ErbB2 overexpressing BT-474 cells, and an arrest in the growth of tumors in animals treated with dual drug-loaded micelles was observed, while both 17-AAG and PTX were used at sub therapeutic doses of 10 mg and 5 mg equivalents per kg body weight. The lower doses also helped avoid toxicity associated with the therapy. We also show the importance of simultaneously delivering the two drugs via a single carrier system as opposed to cocktail of individual drug-loaded micelles administered at equivalent doses, which has a better therapeutic outcome than the cocktail therapy. These combination drug-loaded micelles were developed as a platform for chemotherapy with Trast. The triple therapeutic system of Trast with combination drug-loaded micelles containing 17-AAG and PTX exhibited an even stronger anticancer effect, with complete regression of tumors at the end of treatment, which reached a palpable size again after day 45 with much slower progression than other treatment controls. Pancreatic cancer (PC) is one of the most lethal malignancies, due to aggressive tumorigenicity, early metastasis and development of drug resistance to standard care chemotherapy. Since its approval in 1997, Gemcitabine (Gem) has been the first-line treatment for advanced disease. However, there is no standard second-line therapy after Gem failure. FOLFIRINOX, a combination of four agents, folinic acid, fluorouracil, irinotecan and oxaliplatin was approved by the FDA in 2010. The rationale for this combination was based on these drugs having a different mechanism of action, and, more importantly, non-overlapping toxicities. In cases that could tolerate FOLFIRINOX, an overall improvement in the survival times as well as quality of life was noted. However, even the toxicities are non-overlapping, the cumulative toxicity profile for FOLFIRINOX can become the dose limiting factor. In the first trial itself, 50.8% of the patients needed dose adjustment. The common toxicities observed with FOLFIRINOX include Febrile neutropenia, Thrombocytopenic bleeding, ≥ grade 3 platelets, Grade 2 persistent neurotoxicity, Grade 3 persistent neurotoxicity OR Grade 4 neurotoxicity and many more non-hematological toxicities. Most of the toxicities are severe enough to require discontinuation of the treatment or switching to lower doses or alternative agents. The combination of Gem with Cisplatin (CDDP) has been explored in clinical trials for metastatic disease. As a part of FOLFIRINOX, platinum compounds showed significant efficacy. Cisplatin acts by damaging the DNA. It is known to first get converted into the aqua form within the cell, which happens by the replacement of the labile chloro groups with water molecules. This active form is then able to form covalently linked adducts with the DNA. This initial assault then goes on to activate a series of signaling pathways that ultimately lead to apoptosis and cell death. The DNA adducts thus formed can cause distortion of the DNA and subsequent recognition by various cellular proteins. This leads to problems in DNA synthesis and replication and is reported to cause a prolonged G2 cell-cycle phase arrest. However, the exact mechanism of activation of the apoptotic pathways remains unclear. On the other hand, gemcitabine is a deoxycytidine analog. Its mechanism of activation involves conversion into its triphosphate form, which can then be incorporated into the DNA as a false nucleotide. Usually, one more deoxynucleotide can be incorporated into the DNA before the synthesis stops. Another minor mechanism of action of gemcitabine is its ability to inhibit ribonucleotide reductase, which plays a key role in the repair mechanism of the DNA. Many studies report the benefit of administration of gemcitabine prior to that of cisplatin; the reason cited for this is the increase in the formation of Pt-DNA adducts when the DNA had already been damaged and exposed due to the incorporation of deoxycytidine or active gemcitabine. The gemcitabine in turn inhibits the repair of the formed Pt-DNA adducts as well as reduces the efficacy of nucleotide excision repair by its ability to inhibit the action of ribonucleotide reductase. On the other hand, when Pt compounds are administered prior to gemcitabine, the formed Pt-DNA adducts can no longer allow for the incorporation of gemcitabine and that leaves no scope for gemcitabine to act. Our preliminary in vitro studies with the free drugs on T3M4 Simple Cells (COSMC deleted cells) showed that synergy of the combination is schedule-dependent, and Gem administration followed by CDDP showed the most potent cytotoxic activity. However, this combination proved to be only marginally effective in actual practice due to combined increased toxicity of both the agents. We have shown that encapsulation of CDDP in polymeric nanogels with cross-linked ionic cores enhanced its tumor accumulation and improved its safety profile. Additionally, sustained release profile of CDDP from nanogels allows for the administration of free Gem and CDDP loaded nanogels in a single injection while still retaining schedule-dependent synergy of the combination. Pancreatic ductal adenocarcinoma cells are known to express truncated O-glycans (Tn and STn antigens) and it was shown that decorating the nanogels with an antibody directed against this antigen further enhanced their uptake by tumor cells while reducing off-target accumulation in an in vivo pancreatic cancer model.
Lipid Nanocarriers for Drug Targeting presents recent advances in the area of lipid nanocarriers. The book focuses on cationic lipid nanocarriers, solid lipid nanocarriers, liposomes, thermosensitive vesicles, and cubosomes, with applications in phototherapy, cosmetic and others. As the first book related to lipid nanocarriers and their direct implication in pharmaceutical nanotechnology, this important reference resource is ideal for biomaterials scientists and those working in the medical and pharmaceutical industries that want to learn more on how lipids can be used to create more effective drug delivery systems. Highlights the most commonly used types of lipid nanocarriers and explains how they are applied in pharmacy Shows how lipid nanocarriers are used in different types of treatment, including oral medicine, skin repair and cancer treatment Assesses the pros and cons of using different lipid nanocarriers for different therapies
This book presents the medical challenges that can be reduced or even overcome by recent advances in nanoscale drug delivery. Each chapter highlights recent progress in the design and engineering of select multifunctional nanoparticles.
Nanotechnology can treat diseases by site-specific and target-oriented delivery of precise medicines. Nanomaterials improve the efficacy of drugs and selective diagnosis. The book covers detection and treatment. It explains the use of nanocarriers for a variety of diseases such as cardiovascular and respiratory diseases, cancer, and ulcerative colitis. It includes topical, transdermal, and ocular drug delivery and combined medication delivery.
Author : Alexandru Mihai Grumezescu Publisher : William Andrew Page : 374 pages File Size : 29,12 MB Release : 2017-05-03 Category : Medical ISBN : 0323527264
Multifunctional Systems for Combined Delivery, Biosensing, and Diagnostics explores how multifunctional nanocarriers are being used in combined delivery and diagnostics in contemporary medicine. Particular attention is given to efforts to i) reduce the side effects of therapeutic agents, ii) increase the pharmacological effect, and iii) improve aqueous solubility and chemical stability of different therapeutic agents. The chapters focus on applications of nanostructured materials and nanocarriers, highlighting how these can be used effectively in both diagnosis and delivery. This applied focus makes the book an important reference source for those wanting to learn more about how specific nanomaterials and nanotechnology systems can help to solve drug delivery and diagnostics problems. This book is a valuable resource for materials scientists, bioengineers, and medical researchers who are looking for an applications-oriented guide on how nanotechnology and nanomaterials can be used effectively throughout the medical treatment process, from diagnosis to treatment. Explores the benefits of using a variety of nanomaterials as drug delivery agents Explains how nanocarriers can reduce the side effects of therapeutic agents Provides an analysis of the pros and cons of using specific nanocarriers to solve particular diagnosis and delivery problems
Introducing Smart Nanocarrier for Effective Drug Delivery—a pioneering guide that delves into the realm of nanotechnology and its revolutionary impact on drug delivery systems. This comprehensive volume offers a deep understanding of smart nanocarriers' principles, design, and applications, setting it apart as a cutting-edge resource in the field. Nanotechnology has transformed drug delivery, enhanced therapeutic outcomes, and minimized side effects. This book provides a concise yet thorough overview of this dynamic landscape, elucidating key concepts and methodologies. It covers foundational principles and explores advanced strategies for targeted drug delivery, personalized medicine, and combination therapy. KEY FEATURES In-depth exploration of various types of nanocarriers, from liposomes to polymeric nanoparticles, highlighting their unique attributes. Detailed examination of smart stimuli-responsive nanocarriers that release drugs at precise locations and times. Comprehensive analysis of the latest advancements in nanomedicine, including nanodiagnostics and theranostics. Case studies illustrating real-world applications and success stories of nanocarrier-enhanced drug delivery. Smart Nanocarrier for Effective Drug Delivery is an invaluable resource for researchers, practitioners, and students in pharmaceutical sciences, nanotechnology, and drug delivery. It offers a roadmap to harnessing the potential of nanocarriers for enhancing therapeutic efficacy while minimizing adverse effects. This book equips readers with the knowledge to navigate the rapidly evolving landscape of smart nanocarrier technology, making it an essential addition to their professional toolkit.
This book covers basic aspects of different nanoparticles, including type of materials, lipid, polymeric and inorganic structures, synthesis strategies, as well as the main physicochemical characterization techniques. Moreover, this book addresses applications for both treatment and diagnosis of diseases, highlighting in vitro and in vivo findings and clinical evaluation. The chapters highlight the main barriers for drug delivery which can benefit from nanoencapsulation: the topical and oral routes. The main innovations in the field, such as gene therapy and functionalization of nanoparticles with a variety of moieties, including monoclonal antibodies for selective delivery, are discussed and illustrated with examples. Finally, the application of nanoparticles for drug delivery to cancer is reviewed considering toxicology and regulatory aspects.
Nano-carriers for Drug Delivery: Nanoscience and Nanotechnology in Drug Delivery presents recent discoveries in research on the pharmaceutical applications of the various types of nanosystem-based drug delivery systems. As many nanosystems have reached the market over the past decade, this book proves their benefits to patients. It explores these new carriers and the advances in drug delivery they have facilitated. Reflecting the interdisciplinary nature of the subject matter, the book includes experts from different fields, and with various backgrounds and expertise. It will appeal to researchers and students from different disciplines, such as materials science, technology and various biomedical fields. Coverage includes industrial applications that bridge the gap between lab-based research and practical industrial use. The resulting work is a reference and practical source of guidance for researchers, students and scientists working in the fields of nanotechnology, materials science and technology and biomedical science.