Nanoscale Fabrication, Optimization, Scale-up and Biological Aspects of Pharmaceutical Nanotechnology

Alexandru Mihai Grumezescu

• Publisher: Elsevier
• Year: 2017
• Print ISBN: 9780128136294
• eBook ISBN: 9780128136300
• Topic: Physical Sciences
• Subtopic: Physics
• Index: Physics

Nanoscale Fabrication, Optimization, Scale-up and Biological Aspects of Pharmaceutical Nanotechnology focuses on the fabrication, optimization, scale-up and biological aspects of pharmaceutical nanotechnology. In particular, the following aspects of nanoparticle preparation methods are discussed: the need for less toxic reagents, simplification of the procedure to allow economic scale-up, and optimization to improve yield and entrapment efficiency. Written by a diverse range of international researchers, the chapters examine characterization and manufacturing of nanomaterials for pharmaceutical applications. Regulatory and policy aspects are also discussed.This book is a valuable reference resource for researchers in both academia and the pharmaceutical industry who want to learn more about how nanomaterials can best be utilized.- Shows how nanomanufacturing techniques can help to create more effective, cheaper pharmaceutical products- Explores how nanofabrication techniques developed in the lab have been translated to commercial applications in recent years- Explains safety and regulatory aspects of the use of nanomanufacturing processes in the pharmaceutical industry

Chapter 1

Fabrication of polymeric core-shell nanostructures

Emmanuel O. Akala and Simeon K. Adesina, Howard University, Washington, DC, United States

Abstract

This chapter gives an historical perspectives on nanomedicine: from the first generation nanoparticles—suitable for liver targeting—to the fourth generation dubbed theranostic (multifunctional nanoscale devices which allow for a combination of a diagnostic agent with a therapeutic agent, and a reporter of therapeutic efficacy in the same nanodevice package). The rationale for the development of polymeric core-shell (corona) nanostrurcture is articulated. Materials—natural and synthetic polymers—for the fabrication of polymeric core-shell nanostructures are discussed, together with methods of fabrication and examples. Emphasis was placed on in-situ dispersion polymerization at ambient temperature extensively investigated in our laboratory. Applications of quality by design approach in the fabrication of core-shell nanostructures are presented: by carefully selecting which combinations of the formulation and process variables to evaluate, the properties of core-shell nanostructures can be optimized using statistical design of experiments, followed by computer numerical and graphical optimizations.

Keywords

Core-shell nanostructures; natural-polymers; synthetic-polymers; fabrication-methods; computer-optimization

Chapter Outline

1.1 Introduction 2

1.1.1 Definition and Historical Perspectives on Nanotechnology/Nanomedicine 2

1.1.2 The Rationale for the Development of Polymeric Core-Shell Nanoparticles 3

1.2 Materials for the Fabrication of Polymeric Core-Shell Nanostructures 11

1.2.1 Natural Polymers 12

1.2.2 Synthetic Polymers 12

1.2.3 Materials for the Metallic Core of Core-Shell Nanoparticles 13

1.3 Methods for the Fabrication of Polymeric Core-Shell Nanostructures 14

1.3.1 Methods for Preparation of Nanoparticles From Preformed Polymers 15

1.3.2 In-Situ Polymerization 17

1.4 Dispersion Polymerization the Fabrication of Core-Shell Nanoparticles 21

1.4.1 Mechanism of Dispersion Polymerization 22

1.4.2 Factors Influencing Properties of Particles Produced by Free Radical Dispersion Polymerization 23

1.4.3 In-Situ Dispersion Polymerization at Ambient Temperature Involving Redox Initiator System for the Fabrication of Core-Shell Nanoparticles 27

1.4.4 Examples of Nanoparticles From Our Laboratory Fabricated by Free Radical Dispersion Polymerization at Ambient Temperature Involving Redox Initiator System 27

References 40

Further Reading 49

1.1 Introduction

1.1.1 Definition and Historical Perspectives on Nanotechnology/Nanomedicine

Nanoparticles are submicron (<1 μm) colloidal systems which can be fabricated from varied and diverse materials in a variety of compositions, including quantum dots (QDs), polymers, gold, paramagnetic iron, etc. Over the past few decades, there has been considerable interest in developing nanoparticles as effective drug delivery devices. Thus, the awareness of the usefulness of nanotechnology in novel drug delivery systems has existed before the recent upsurge of interest in nanotechnology all over the world. This is exemplified by Peter Paul Speiser, who developed the first nanoparticles which can be used for targeted drug therapy at the end of the 1960s (Kreuter, 2007; Krukemeyer et al., 2015). The advent of new and sophisticated tools, such as atomic and electron microscopes, has allowed scientists to gain in depth understanding of nanostructured substances. Recent advances in the field of nanotechnology have made nanoparticles very promising in the delivery and targeting of bioactive agents, drug discovery and diagnostics. In fact, nanotechnology is one of the key technologies of the 21st century (Krukemeyer et al., 2015).

The progress in the development of nanoparticles for biomedical applications has moved from the first generation nanoparticles—mainly suitable for liver targeting, as they are captured in the liver by the reticuloendothelial system (RES), also known as mononuclear phagocyte system (MPS); into the second generation, stealth nanoparticles: the nanoparticle surface is decorated or tagged with water soluble polymers, especially polyethylene glycol (PEG) for long systemic circulation and passive targeting (sequestration of the nanoparticles into the leaky vasculature of the tumor blood vessels, followed by their retention—enhanced permeability and retention (EPR) effect); to the third generation nanoparticles, with targeting moiety. The nanoparticle surface is decorated with a ligand specific for the antigen or receptor expressed on the surface of the tumor cells (Hillareau and Couvreur, 2006; Akala, 2010; Ogunwuyi et al., 2015). Fourth generation nanoparticles have been dubbed theranostic: multifunctional nanoparticles which allow for a combination of diagnostic agent with a therapeutic agent and a reporter of therapeutic efficacy in the same nanodevice package (Kelkar and Reineke, 2011).

The evolution of polymeric nanoparticles reflects their advantages. Polymeric nanoparticles can help to increase the stability of bioactive agents. They can be used to provide targeted (cellular/tissue) delivery of drugs, to improve oral bioavailability, to sustain drug/gene effect in target tissue, to solubilize drugs for intravascular delivery, and to improve the stability of therapeutic agents against enzymatic degradation (nucleases and proteases). Due to their sub-cellular and sub-micron size, nanoparticles can penetrate deep into tissues through fine capillaries, cross the fenestration present in the epithelial lining (e.g., liver), and are generally taken up efficiently by cells, thereby allowing the efficient delivery of therapeutic agents to target sites in the body. By also modulating polymer characteristics (e.g., via crosslinking), it is possible to control the release of a therapeutic agent from nanoparticles to achieve desired therapeutic level in the target tissue for the required duration for optimal therapeutic efficacy. Further, nanoparticles can be delivered to distant target sites either by localized delivery using a catheter-based approach with a minimal invasive procedure, or they can be conjugated to a biospecific ligand, which would direct them to the target tissue or organ. Nanoparticles with appropriate ligands attached to their surfaces are also useful for the delivery of bioactive agents after binding to target cellular receptors by a mechanism called receptor-mediated endocytosis. Another characteristic function of nanoparticles is their ability to deliver drugs across several biological barriers to the target site. Drug delivery to the brain for a wide variety of drugs, such as antineoplastics and anti-HIV drugs, is markedly hindered because they have great difficulty in crossing the blood-brain barrier (BBB). The application of nanoparticles to brain delivery is a promising way of overcoming this barrier. It was recently demonstrated that poly(butylcyanoacrylate) nanoparticles coated with polysorbate-80, are effective in transporting the hexapeptide dalargin and other agents into the brain (Hillareau and Couvreur, 2006; Bro and Hunziker, 2007).

1.1.2 The Rationale for the Development of Polymeric Core-Shell Nanoparticles

Polymeric nanoparticles can be broadly classified into two: nanocapsules, which are reservoir or vesicular systems in which a liquid or semisolid drug-loaded core is surrounded by a polymeric membrane; or nanospheres which are matrix systems in which the drug is uniformly dispersed throughout a solid polymer matrix (core). In both systems, the nanoparticle surface (corona) may be tagged with polymers, especially hydrophilic polymers (Vauthier and Bouchemal, 2009; Mishra and Patel, 2010; Rao and Geckeler, 2011).

1.1.2.1 Drug solubility enhancement

Nanoparticles may be used to enhance the solubility of poorly water soluble drugs (especially anticancer drugs) (Yanasarn et al., 2009). Paclitaxel and docetaxel are poorly water soluble. Their incorporation into poly(lactide) or polycaprolactone hydrophobic nanoparticle core circumvented this problem (Adesina et al., 2014a; Ogunwuyi et al., 2015). This was also exemplified by Abraxane for injectable suspension (palclitaxel albumin-bound nanoparticles) (Sparreboom, 2005).

1.1.2.2 Combination drug therapy and mod...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of Contributors
• Series Preface: Pharmaceutical Nanotechnology
• Preface
• Chapter 1. Fabrication of polymeric core-shell nanostructures
• Chapter 2. The emulsification-diffusion method to obtain polymeric nanoparticles: Two decades of research
• Chapter 3. Tools and techniques for the optimized synthesis, reproducibility and scale up of desired nanoparticles from plant derived material and their role in pharmaceutical properties
• Chapter 4. Scale up of biopharmaceuticals production
• Chapter 5. Physicochemical and morphological characterization of pharmaceutical nanocarriers and mathematical modeling of drug encapsulation/release mass transfer processes
• Chapter 6. Biopharmaceutics and pharmacokinetics of multifunctional nanoparticles
• Chapter 7. Technological delivery systems to improve biopharmaceutical properties
• Chapter 8. From physicochemically stable Nanocarriers to targeted delivery: In vivo pharmacokinetic, pharmacodynamic and biodistribution studies
• Chapter 9. Sterile dosage forms loaded nanosystems for parenteral, nasal, pulmonary and ocular administration
• Chapter 10. Quantitative characterization of targeted nanoparticulate formulations for prediction of clinical efficacy
• Chapter 11. Analytical tools for reliable in vitro and in vivo performance testing of drug nanocrystals
• Chapter 12. Application of affinity purification of drug target proteins with practical magnetic nanoparticles to drug development
• Chapter 13. Molecularly imprinted polymers as a tool for biomolecule separation
• Chapter 14. Detection of DNA damage induced by nanomaterials
• Chapter 15. Pharmacological usage of a selective inhibitor of 3-mercaptopyruvate sulfurtransferase to control H2S and polysulfide generation
• Chapter 16. Nanotechnology-based drug products: Science and regulatory considerations
• Index