Advances in Nanomedicine for the Delivery of Therapeutic Nucleic Acids

Advances in Nanomedicine for the Delivery of Therapeutic Nucleic Acids

1st Edition - April 4, 2017

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  • Authors: Surendra Nimesh, Ramesh Chandra, Nidhi Gupta
  • Hardcover ISBN: 9780081005576
  • eBook ISBN: 9780081005637

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Description

Advances in Nanomedicine for the Delivery of Therapeutic Nucleic Acids addresses several issues related to safe and effective delivery of nucleic acids (NAs) using nanoparticles. A further emphasis would be laid on the mechanism of delivery of NAs, the barriers encountered and the strategies adapted to combat them. An exhaustive account of the advantages as well shortcomings of all the delivery vectors being employed in delivery of various NAs will be provided. On final note the regulatory aspects of nanoparticles mediated NA would be discussed, with focus on their clinical relevance.  The design and development of nucleic acid-based therapeutics for the treatment of diseases arising from genetic abnormalities has made significant progress over the past few years. NAs have been widely explored for the treatment of cancer and infectious diseases or to block cell proliferation and thereby caused diseases. Advances in synthetic oligonucleotide chemistry resulted in synthesis of NAs that are relatively stable in in vivo environments. However, cellular targeting and intracellular delivery of NAs still remains a challenge. Further development of NA-based therapeutics depends on the progress of safe and effective carriers for systemic administration. Nanomedicine has facilitated availability of vectors with diminished cytotoxicity and enhanced efficacy which are rapidly emerging as systems of choice. These vectors protect NAs from enzymatic degradation by forming condensed complexes along with targeted tissue and cellular delivery. During the past few years, a myriad reports have appeared reporting delivery of NAs mediated by nanoparticles. This book will provide an overview of nanoparticles being employed in the in vitro and in vivo delivery of therapeutically relevant NAs like DNA, siRNA, LNA, PNA, etc.

Key Features

  • Provides a complete overview of the applicatiosn of nanomedicine in the delivery of nucleic acids, from characterization of nanoparticles, to in vitro and in vivo studies
  • Discusses delivery issues of less well explored nucleic acids, like PNAs, Ribozymes, DNAzymes, etc.
  • Summarizes the current state of research in nucleic acid delivery and underscores the future of nanomedicine in this field

Readership

Professors and graduate students in therapeutic nanomedicine; researchers in nanomedicine and nucleic acids

Table of Contents

  • 1. Nanomedicine for delivery of therapeutic molecules

    • 1.1. Introduction
    • 1.2. Properties of nanoparticles
    • 1.3. Polymeric nanoparticles
    • 1.4. Nanoparticle-based strategies for overcoming in vitro and in vivo barriers
    • 1.5. Book compilation

    2. Nanoparticles as nucleic acid delivery vectors

    • 2.1. Introduction
    • 2.2. Challenges and barriers to the nucleic acid delivery
    • 2.3. Vectors in nucleic acid delivery
    • 2.4. Nanoparticles as nonviral nucleic acid delivery vectors
    • 2.5. Conclusion and future prospects

    3. Methods for characterization of nanoparticles

    • 3.1. Introduction and challenges in nanoparticle characterization
    • 3.2. Techniques and approaches to nanoparticle characterization
    • 3.3. Stability evaluation of nanoparticles
    • 3.4. Sterility assessment of nanoparticles

    4. Nanoparticles for DNA delivery

    • 4.1. Introduction
    • 4.2. Low molecular weight linear polyethylenimine
    • 4.3. High molecular weight linear polyethylenimine
    • 4.4. Low molecular weight branched polyethylenimine
    • 4.5. High molecular weight branched polyethylenimine

    5. Nanoparticles for siRNA-mediated gene silencing

    • 5.1. Introduction
    • 5.2. Chitosan
    • 5.3. Polyethylenimine
    • 5.4. Poly-l-lysine
    • 5.5. Dendrimers
    • 5.6. Cyclodextrins
    • 5.7. Poly(lactic-co-glycolic) acid

    6. Nanoparticles for locked nucleic acid delivery

    • 6.1. Introduction
    • 6.2. Locked nucleic acids: structure
    • 6.3. Locked nucleic acids: hybridization and conformation properties
    • 6.4. Serum stability and nuclease resistance
    • 6.5. Delivery and toxicity
    • 6.6. Therapeutic applications of locked nucleic acids
    • 6.7. Nanoparticle-mediated delivery of locked nucleic acid and locked nucleic acid-modified oligonucleotides
    • 6.8. Conclusion and future prospects

    7. Nanoparticles for ribozymes delivery

    • 7.1. Introduction
    • 7.2. Types of ribozymes
    • 7.3. Ribozymes and their limitations
    • 7.4. Selection of the target gene
    • 7.5. Stability of ribozymes
    • 7.6. Delivery of ribozymes
    • 7.7. Applications of RNA nanoparticles emphasizing ribozymes
    • 7.8. Conclusion and future prospects

    8. Nanoparticles for DNAzymes delivery

    • 8.1. Introduction
    • 8.2. DNAzymes
    • 8.3. The 10–23 DNAzymes
    • 8.4. The 8–17 DNAzymes
    • 8.5. Mechanism of DNAzymes
    • 8.6. Advantages of DNAzymes
    • 8.7. Stability of DNAzymes
    • 8.8. Application of DNAzymes
    • 8.9. DNAzyme delivery via metallic and polymeric nanoparticles
    • 8.10. Conclusion and future prospects

    9. Pharmacokinetics and biodistribution of the nanoparticles

    • 9.1. Introduction
    • 9.2. Pharmacokinetics of nanoparticles
    • 9.3. Generalized pharmacokinetic profile of various nanoparticles
    • 9.4. Challenges and future prospects
    • 9.5. Conclusions

    10. Nanotoxicology: Evaluation of toxicity potential of nanoparticles

    • 10.1. Introduction
    • 10.2. Size of nanoparticles
    • 10.3. Dose-dependent toxicity
    • 10.4. Nondosage-dependent actions/route
    • 10.5. Surface area-dependent toxicity
    • 10.6. Concentration-dependent toxicity
    • 10.7. Particle chemistry and crystalline structure-dependent toxicity
    • 10.8. Aspect ratio-dependent toxicity
    • 10.9. Surface coating and functions attributed
    • 10.10. Risk management of nanotechnology-specific aspects
    • 10.11. Conclusion and future prospects

    11. Regulatory aspects of nanoparticulate mediated nucleic acid delivery systems

    • 11.1. Introduction
    • 11.2. Issues related with nanoparticle mediated nucleic acid delivery systems
    • 11.3. Current approaches for regulating pharmaceutical nanoparticles

    12. Clinical studies and future prospects

    • 12.1. Introduction
    • 12.2. Regulatory pathways in the process of clinical trials
    • 12.3. Barriers in the progress of clinical trials
    • 12.4. Ethical concerns in clinical trials
    • 12.5. Nanotherapeutics in clinical trials
    • 12.6. Conclusion

Product details

  • No. of pages: 256
  • Language: English
  • Copyright: © Woodhead Publishing 2017
  • Published: April 4, 2017
  • Imprint: Woodhead Publishing
  • Hardcover ISBN: 9780081005576
  • eBook ISBN: 9780081005637

About the Authors

Surendra Nimesh

Dr. Surendra Nimesh is the author/co-author of two Elsevier books: The Design and Development of Novel Drugs and Vaccines (2021) and Gene Therapy: Potential Applications of Nanotechnology (2013) an internationally recognized expert of nanotechnology for biological applications with specialization in drug and gene delivery. He received his M.S. in Biomedical Science from Dr. B.R. Ambedkar Center for Biomedical Science Research (ACBR), University of Delhi, Delhi, India in 2001. He completed his PhD. in Nanotechnology at ACBR and Institute of Genomics and Integrative Biology (CSIR), Delhi, India in 2007. After completing his postdoctoral studies at Ecole Polyetchnique of Montreal, Montreal in 2009, he joined Clinical Research Institute of Montreal, Montreal, Canada as Postdoctoral Fellow. He worked for a short duration at McGill University, Montreal and thereafter joined Health Canada, Canada as NSERC visiting fellow in 2012. He joined Central University of Rajasthan, India as UGC-Assistant Professor at Department of Bitechnology, School of life Sciences in 2013. He has authored more than 20 research papers, 10 review articles in international peer reviewed journal, 8 book chapters and 3 books. His research interests include nanoparticles mediated gene, siRNA and drug delivery for therapeutics.

Affiliations and Expertise

UGC Assistant Professor, Department of Biotechnology, School of Life Sciences, Central University of Rajasthan, India

Ramesh Chandra

Affiliations and Expertise

Ambedkar Center for Biomedical Research & Department of Chemistry, University of Delhi, India

Nidhi Gupta

Dr. Nidhi Gupta received her M.S. in Biomedical Science from Dr. B.R. Ambedkar Center for Biomedical Research (ACBR), University of Delhi, Delhi, India in 2004. She did her PhD. with Dr. A.C. Banerjea at National Institute of Immunology (NII), New Delhi, India in 2008. After completing her doctoral research she joined Clinical Research Institute of Montreal, Montreal, Canada as Postdoctoral Fellow in 2008 and later worked at McGill University, Montreal. She joined The IIS University, India as Research Scientist at Department of Biotechnology in 2014. Her field of interest includes catalytic nucleic acids, siRNA and antisense.

Affiliations and Expertise

The IIS University, India

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