Cookie policy: This site uses cookies (small files stored on your computer) to simplify and improve your experience of this website. Cookies are small text files stored on the device you are using to access this website. For more information please take a look at our terms and conditions. Some parts of the site may not work properly if you choose not to accept cookies.

Join

Subscribe or Register

Existing user? Login

Nanotechnology medicine — from gene delivery to tissue targeting

There is no question that nanotechnology will become increasingly more important in the future of medicine. Hamde Nazar describes some exciting developments

By Hamde Nazar

There is no question that nanotechnology will become increasingly more important in the future of medicine. Hamde Nazar describes some exciting developments

Nanotechnology refers to the science and engineering involved in the design, synthesis, characterisation and application of materials and devices whose smallest functional dimension is on the nanometer scale (one-billionth of a metre). For some perspective, a human hair is approximately 80,000nm and a red blood cell is 7,000nm wide. The explosive development in this field was initially driven by the electronic industry’s interest in miniaturisation of tools, for faster and more complex functionality of electronic devices on silicon chips.1

Within the realms of health, nanomedicine and pharmaceuticals can be exploited in the processes of monitoring, repairing, constructing and involvement in the control of biological systems at the nanometre level. This scientific area offers an unprecedented opportunity for the rational delivery of vaccines and drugs to the desired target in the body following oral or systemic administration.
The potential nanosystems that have been designed demonstrate the flexibility and adaptability towards different compositions and biological properties. Examples of these systems include:

Nanoparticles Nanoparticles encompass particulate matter of the nano-size that can be polymeric or lipid-based (liposomes, nanoemulsions and solid-lipid nanoparticles). It is a term that is used interchangeably with the plethora of system types that exists.
Dendrimers Dendrimers are highly branched, star-shaped molecules with nanometer-scale dimensions. They have the general structure of a central core, an interior branched layer and an outer surface with functional surface groups.
Nanocages Nanocages are nanostructures that have hollow interiors and porous walls and tend to be made from metals that are resistant to corrosion and oxidation in moist air.
Micelles Micelles are structures that form when lipid molecules arrange themselves in a spherical manner in aqueous solutions.
Molecular conjugates Molecular conjugates are nano-sized systems comprised of synthetic materials (eg, lipids, targeting agents) constructed for the delivery of nucleic acids.
Liposomes Liposomes are spherical vesicles that consist of a lipid bilayer.

The advantages of such structures, apart from their small particle size and narrow size distribution, are:2

• The potential for surface modification for target-specific localisation
• The protective insulation of drug molecules to enhance stability
• The opportunity to develop nanocarriers that respond to physiological stimuli (pH, enzymes, immune system)
• The feasibility of delivery of multiple therapeutic agents in a single formulation
• The combination of imaging and drug therapy to monitor effects in real time
• The opportunity to combine drugs with energy (heat, light and sound) delivery for synergistic therapeutic effects

The modification of the properties of the nanocarrier (eg, particle and surface charge) will determine the biodistribution and pharmacokinetic profile within the body, where specific alterations can facilitate transport across biological barriers (eg, mucosal membranes, lipophilic cell membranes, etc).

The increased knowledge and understanding of the biological systems and processes, with identification of cell-surface receptors, molecular mechanisms and depth within the pathophysiology of diseases, has led to a general shift from the generic development and synthesis of novel systems towards a design process that is rationalised and tailored.3

Drug delivery

Nanosystems have been developed via this rational process within varied Recently there have been developments to enhance DNA entrapment in nanoparticles for gene deliveryapproaches of drug delivery. Below are a few examples.

Intracellular trafficking

The systems are of a size small enough to be taken up more efficiently by cells than the larger microparticles. The released therapeutic agent may have an effect on targeted intracellular organelles, such as mitochondria, nucleus and endo-lysosomes, that play a role in the pathophysiology of the disease being treated. For example, the cytoplasm is a target site for glucocorticoids, and antibiotics are rendered more effective at targeting intracellular residing infective agents. The overarching achievement through the challenging design of nanoparticles or other systems to target intracellular compartments or receptors is to reduce the non-specific effects of the drugs and also to potentiate their therapeutic efficacy.3 Surface charge of these nanovehicles is also important for cellular entry, where cationic (positively charged) particles will promote interaction with negatively charged surfaces of cells to increase rate and extent of entry.4

Gene delivery

Plasmid DNA and siRNA have recently been developed as novel nucleic acid-based innovative medicines. Their clinical application is disadvantaged by their inherent instability under physiological conditions, as well as low cellular uptake due to their large molecular weight and anionic nature. Direct administration into the blood stream results in rapid elimination, usually driven by DNAse and RNAse.

The intracellular transporting capability of nanocarriers has been exploited to accumulate these agents in the nucleus of cells where they are required for therapeutic effect. Non-viral vectors, such as the polymers and lipids of nanocarriers, offer a superior alternative to the viral vectors (retroviruses, adenoviruses and adeno-associated vectors) in terms of cost, safety and mass production.5

It has been demonstrated that nanoparticles can protect the therapeutic agent from degradation due to lysosomal enzymes to release encapsulated DNA at a sustained rate, resulting in sustained gene expression. Most recently, there have been developments to enhance DNA entrapment in nanoparticles by condensing them before encapsulation, or synthesising novel polymers with cationic groups that would condense DNA into the matrix. This would allow smaller doses of nanoparticles to be administered for effective therapeutic benefit.4

Mucosal delivery

Another broad application of nanotechnology is in the delivery of antigens for vaccinations. Mucosal immunity has been acknowledged as extremely important in disease prevention but has been somewhat limited due to the degradation of the vaccine and its limited uptake. Encapsulation of these vaccines into either nano- or microparticles has demonstrated enhanced immune response in animal models. For example, the M-cells in the Peyer’s patches of the distal small intestine have displayed the capability to engulf both nano- and micro particles to demonstrate the potential of oral delivery of vaccines.1 The nasal mucosa, with its associated lymphoid tissue, can also be targeted by nanoparticles, which will be taken up by M-cells to result in both local and systemic immune responses.

Tissue targeting

Targeting therapeutic agents to specific tissues has become possible through the development of monoclonal antibodies, the identification of specific receptors that are either over- or selectively expressed in specific tissues, and the discovery of conjugation techniques to attach antibodies or ligands to the nano-sized drug delivery systems.6 The reduction in side effects and the higher bioavailability of the drug at the site of action is the desired result. For example, coupling high molecular weight macromolecules passively targets the nanosystem to tumour tissue due to the enhanced permeation and retention effect. This is attributed to the hyperpermeability of the newly formed blood vessels within the mass.2

Also, coating nanocarriers with hydrophilic polymers will repel plasma proteins and macrophages that potentially aggregate to form larger particles but also potentiate the risk of clearance by circulating macrophages.6 The use of a specific stimuli-sensitive delivery system that releases the encapsulated payload once exposed to the stimuli trigger can be exploited. The pH around tumours and other hypoxic tissues tends to be more acidic relative to the physiological pH of 7.4. This environment has shown to cause accumulation of pH-sensitive nanoparticles at the tumour site. Modifying nanocarriers with polyethylene glycol has rendered particles resistant to clearance by the cells of the immune system that could otherwise engulf and eliminate them before therapeutic drug release.
These protected vehicles are described as stealth vehicles and have enhanced circulation time and can achieve tissue targeting. Modifying the surface of these systems with nutrients such as folic acid, specific vitamins or sugars can achieve active targeting towards tumour cells that tend to have over-expression of receptors for such nutrients.2

Summary

Nanotechnology promises to be extremely important for the future of medicine. The ideal nanosystems for the delivery of a drug should achieve a long circulation time, low immunogenicity, good biocompatibility, selective targeting, and the efficient penetration of barriers such as the vascular endothelium and the robust blood-brain barrier. With these objectives met, we will potentially enter into an area of tailored medicines for specific effects at target sites, with reduced side effects and improved therapeutic efficacy.

However, despite the widely publicised benefits and opportunities, concerns have been raised relating to the safety of nanomaterials in a variety of products, with some analogies being made to the toxicities of asbestos fibres. Although some may say that these concerns are unsubstantiated, it remains true that significant evaluation of the toxicological profiles of some nanomaterials still does not exist. This, along with the knowledge that nanomaterials, by their very design, are able to enter the human body through a variety of ports, has drawn some caution to their unquestionable widespread use.


Hamde Nazar is senior lecturer in pharmacy practice at the University of Sunderland (email hamde.nazar@sunderland.ac.uk)

 
References

1 Sahoo SK, Parveen S, Panda JJ. The present and future of nanotechnology in human health care. Nanomedicine: Nanotechnology, Biology, and Medicine 2007;3:20–31.
2 Amiji M. Nanotechnology — improving targeted delivery. Available at www.touchbriefings.com (accessed 28 December 2012).
3 Labhasetwar V. Nanotechnology for drug and gene therapy: the importance of understanding molecular mechanisms. Current Opinion in Biotechnology 2005;16:674–80.
4 Panyam J, Labhasetwar V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Advanced Drug Delivery Reviews 2003;55:329–47.
5 Osada K, Christie RJ, Kataoka K. Polymeric micelles from poly(ethylene glycol)-poly(amino acid) block copolymer for drug and gene delivery. Journal of the Royal Society Interface 2009;6:S325–39.
6 Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles based drug delivery systems. Colliods and Surfaces B: Biointerfaces 2010;75:1–18.

Advertisement

Citation: The Pharmaceutical JournalURI: 11115976

Have your say

For commenting, please login or register as a user and agree to our Community Guidelines. You will be re-directed back to this page where you will have the ability to comment.

Recommended from Pharmaceutical Press

Search an extensive range of the world’s most trusted resources

Powered by MedicinesComplete
  • Print
  • Share
  • Comment
  • Save

Jobs you might like

See more jobs

Newsletter Sign-up

Get the latest emails sent to your inbox.