Nanostructures for the Engineering of Cells, Tissues and Organs

From Design to Applications

Alexandru Mihai Grumezescu

• Publisher: William Andrew
• Year: 2018
• Print ISBN: 9780128136652
• eBook ISBN: 9780128136669
• Topic: Physical Sciences
• Subtopic: Physics
• Index: Physics

Nanostructures for the Engineering of Cells: Tissues and Organs showcases recent advances in pharmaceutical nanotechnology, with particular emphasis on tissue engineering, organ and cell applications. The book provides an up-to-date overview of organ targeting and cell targeting using nanotechnology. In addition, tissue engineering applications, such as skin regeneration are also discussed. Written by a diverse range of international academics, this book is a valuable research resource for researchers working in the biomaterials, medical and pharmaceutical industries.- Explains how nanomaterials regulate different cell behavior and function as a carrier for different biomolecules- Shows how nanobiomaterials and nanobiodevices are used in a range of treatment areas, such as skin tissue, wound healing and bone regeneration- Discusses nanomaterial preparation strategies for pharmaceutical application and regenerative medicine

Chapter 1

Cell and organ drug targeting

Types of drug delivery systems and advanced targeting strategies

Imane Himri and Abdelkarim Guaadaoui, University Mohammed Premier, Oujda, Morocco

Abstract

One of the big expectations of nanomedicines is progression in optimized and targeted delivery of drugs to diseased tissue without affecting the original characteristics of the tissue. Accordingly, a smart approach to increase the therapeutic index of a drug is to specifically deliver the therapeutic molecule in its active form, not only into target tissue, nor even to target organs, but more importantly, into the targeted cells.

Drug therapy is based on the prototype that drug will selectively define its pharmacological activity to make the diseased person free from negative side effects and decrease the symptoms and/or cause of the disease. However, the real obstruction associated with systemic drug administration is the lack of target-specific affinity toward a pathological site, resulting in systemic toxicity and countless other side effects, as well as higher dosage requirement for efficacy. As a consequence, it is of major importance that a drug is delivered directly to its site of action within the target cell, while keeping the molecule intact. Drug delivery systems can specifically target tissue and organs of interest as well as different type of cells.

Keywords

Brain; cancer; dendrimer; drug; eye; liposomes; lung; nanocarrier; nanoparticle; neoplastic disease; PEGylation; targeting

Chapter Outline

• 1.1 Introduction 1
• 1.2 Drug Targeting: What, Why and How? 2
  • 1.2.1 Definition and Reasons for Drug Targeting 2
  • 1.2.2 Drug Targeting Strategies 4
  • 1.2.3 Properties Influencing Drug Targeting 20
• 1.3 Cellular Targeting: Normal Cells and Abnormal Cells 30
• 1.4 Organ Targeting 31
  • 1.4.1 Drug Delivery to Brain 31
  • 1.4.2 Drug Delivery to Lung 32
  • 1.4.3 Drug Delivery to Eye 35
  • 1.4.4 Drug Delivery to Neoplastic Disease 37
• 1.5 Conclusion 39
• Glossary 39
• Abbreviations 40
• References 41

1.1 Introduction

Nanotechnology is a multidisciplinary branch which consists of manufacturing nanometer-sized structures and materials. It combines the elements of molecular biology, engineering and chemistry. Nanotechnology is one of the most dynamically developing branches of science and technology (Niemirowicz and Car, 2012). In the past two decades, nanotechnology has been developing quickly and is widely used in medical sciences, specifically for disease diagnosis and treatment (Desai, 2012; Gao, 2016).

Delivering drugs or biocompounactives to the target site is a major problem in the treatment of many diseases (Wilczewska et al., 2012). Reducing the size of a selected material to nanometric scale makes it possible to utilize them in numerous potential applications, including drug targeting (Niemirowicz and Car, 2012).

Recent developments in nanotechnology have shown that nanostructures have great potential as drug carriers. Due to their small sizes, nanocarriers exhibit unique physicochemical and biological properties that make them a favorable material for biomedical applications (Wilczewska et al., 2012). The pharmacokinetic behavior of the drug-loaded nanocarriers depends on the nanosystems and the modes of targeting (passive or active) (Martin Schäffler et al., 2014).

1.2 Drug Targeting: What, Why and How?

1.2.1 Definition and Reasons for Drug Targeting

Drug targeting is a nano-biotechnological method of delivering a biocompounactive (bioactive compound) or an active pharmaceutical ingredient to a patient, in order to increase its concentration in the intended site of action, in a specific part of diseased tissue, and avoiding interaction with healthy tissues. This nano-pharmaceutical method requires various disciplines (biologists, chemists, engineers, etc.) and is believed to improve efficacy, while reducing side effects (maximum efficacy with minimal toxicity).

The drug discovery process has been accelerated with the development of modern technology in pharmaceutical chemistry and molecular biology (i.e., drug design, combinatorial chemistry, high throughput screening, etc.). Nevertheless, this increase in complexity does not necessarily offer more efficient drugs, even if these molecules often possess physicochemical and/or biological characteristics that make their use suboptimal in humans (Bertrand and Leroux, 2012; Chang et al., 2015).

In fact, new drug candidates often exhibit many problems and challenges such as: (1) poor solubility, (2) insufficient in vitro stability (shelf life), (3) too low bioavailability, (4) too short in vivo stability (half-life), (5) strong side effect, (6) need for targeted delivery, (7) regulatory issues/hurdles, and/or (8) lack of large-scale production (Muller and Keck, 2004; Chang et al., 2015). Consequently, the introduction of biotechnological methods for the production of drugs delivery brought a revolution to this biopharmaceutical field for advanced drug development (Muller and Keck, 2004).

In chemotherapy, for example, which remains the main form of treatment for cancer, only a small portion of drugs administered typically reach the organ to be affected (the tumor) since there is no clinically available antineoplastic drug that acts selectively on the tumor mass. For this reason, the scientific research is focused towards the development of novel cancer therapies and drug delivery strategies, such as drug targeting, that would enhance the therapeutic efficacy of drugs while reducing their side effects (Basile et al., 2012).

Moreover, to reach the site of action, the biocompounactive has to transit many biological barriers, such as organs, cells, and intracellular compartments (blood, kidney, liver, spleen, etc.), where it can be inactivated or express undesirable effects on organs and tissues that are not involved in the pathological process. As a result, to achieve a required therapeutic concentration of an active pharmaceutical ingredient in a certain body compartment or certain tissue, one has to administer the drug in large quantities (thus increasing the cost of the therapy), the great part of which, even in the best case scenario, is wasted in normal tissues; cytotoxic and/or antigenic/immunogenic agents can become the cause of many negative side effects. Drug targeting can bring a solution to all these problems (Torchilin, 2010; Bertrand and Leroux, 2012).

The main goal of drug targeting is to localize, target, prolong, and have a protected drug interaction with the diseased tissue (Fig. 1.1). Drug targeting may resolve many problems currently associated with systemic drug administration (orally or as injectables), such as: (a) pharmaceuticals biodistribution, (b) the necessary dose of a drug, (c) lacking affinity between drug-pathological site, (d) the adverse side effects, etc. (Torchilin, 2000; Mishra et al., 2013).

Figure 1.1 Reasons for drug targeting as referred by Agnihotri et al. (2011)-modified.

1.2.2 Drug Targeting Strategies

1.2.2.1 Common approaches of targeted drug delivery

Targeted drug delivery is the ability of the drug to accumulate in the target tissue or organ selectively and quantitatively, independent of the site and methods of administrations. The aim of targeted drug delivery is to obtain high local concentrations of drug in the target area without any side effects in normal tissues, together with low systemic exposure (Fallis, 2002; Hirsjärvi et al., 2011; Mishra et al., 2013).

Targeting may have spatial and temporal properties which deliver the right amount of drug to the right place (double-targeting) (Goodman et al., 2008; Shaji and Lal, 2013). Consequently, targeted drug delivery presents many advantages, the most important of which are (Fallis, 2002):

1. (1) simplification of administration protocols;
2. (2) drastic reduction in the cost of therapy and drug quantity required to achieve a therapeutic effect; and
3. (3) sharp increase in drug concentration in the required sites without negative effects on nontarget areas.

Currently, the principal strategies of drug targeting include many schemes (Torchilin, 2000). Among these various approaches, passive and active targeting seem to be most advanced, and could be relied onto achieve organ-based targeting (first order), specific cell-based targeting in an organ (second order) and cell organelle-based targeting (third order) (Torchilin, 2000, 2010; Danhier et al., 2010). Both passive and active drug targeting reduce toxic side effects, increase effi...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of Contributors
• Series Preface: Pharmaceutical Nanotechnology
• Preface
• Chapter 1. Cell and organ drug targeting: Types of drug delivery systems and advanced targeting strategies
• Chapter 2. Cell-penetrating peptides in nanodelivery of nucleic acids and drugs
• Chapter 3. The current perspectives of nanoparticles in cellular and organ-specific drug targeting in biological system
• Chapter 4. Precision medicine and drug targeting: The promise versus reality of target-specific drug delivery
• Chapter 5. Brain targeting of payload using mild magnetic field: Site specific delivery
• Chapter 6. Nanoparticles influence in skin penetration of drugs: In vitro and in vivo characterization
• Chapter 7. DNA aptamer-based molecular nanoconstructions and nanodevices for diagnostics and therapy
• Chapter 8. Nanobiodevices for electrochemical biosensing of pharmaceuticals
• Chapter 9. Imprinted polymeric nanoparticles as nanodevices, biosensors and biolabels
• Chapter 10. Poly(lactic-co-glycolic acid) (PLGA) matrix implants
• Chapter 11. Hydrogels for biomedical applications
• Chapter 12. Silk-based matrices for bone tissue engineering applications
• Chapter 13. Implantable drug delivery systems: An overview
• Chapter 14. Nanobionics and nanoengineered prosthetics
• Index