NOVEL DRUG DELIVERY SYSTEM
several studies on the toxicity of specific nanoparticles (fullerenes, carbon nanotubes, quantum dots …) are available.
Figure: 20 Prediction of total and regional deposits of particles in the airway according to particle size (41). Reproduced with the authorization of INRS-France
Quantitative assessment of the risk of exposure to nanoparticles
Figure: 21 Effects of nanopareticles
The international experts assembled by the European Commission are unanimous that the potential deleterious effect of nanoparticles cannot be predicted from the toxicity of bulk materials of the same chemical composition but of greater size.
The risk assessment cannot be established precisely, since the dose-response relationships are insufficiently known. For most of the particles that can become airborne and breathed in, the primary concern is the potential damage to the respiratory system, which represents the most likely absorption route in the work environment.
The solubility of the particles directly affects their toxicity and the way they must be assessed or analyzed. In the presence of soluble particles, the entire mass deposited in the pulmonary air passages will quickly become available by dissolution in the biological fluids. This mechanism is well known for particles of larger dimensions. It is the same for nanoparticles. For soluble particles, the assessment of the total mass concentration of these particles thus will become a good indicator of their toxicity.
However, insoluble or low solubility particles will retain their form and expose their surface to the host organism. It then becomes important to document the specific toxicity of these insoluble or low solubility nanoparticles. In the absence of adequate knowledge, attention should also be paid to the cutaneous system and the possibility of ingestion of nanoparticles, particularly by adopting strictly hygienic safety measures.
To assess the potential human health effects of nanoparticles, it is important to develop knowledge that can provide answers to several questions. Specifically, it is essential to document how nanoparticles are absorbed into the human body by several routes (pulmonary, cutaneous and gastrointestinal), how nanoparticles are distributed in the body (blood, lymphatic system), the organs in which nanoparticles tend to accumulate significantly (lungs, brain, kidneys, liver…), and how nanoparticles are metabolized and then eliminated.
8. Future Opportunities and Challenges
Nanoparticles and nanoformulations have already been applied as drug delivery systems with great success; and nanoparticulate drug delivery systems have still greater potential for many applications, including anti tumour therapy, gene therapy, AIDS therapy, radiotherapy, in the delivery of proteins, antibiotics, virostatics, vaccines and as vesicles to pass the blood-brain barrier.
Nanoparticles provide massive advantages regarding drug targeting, delivery and release and, with their additional potential to combine diagnosis and therapy, emerge as one of the major tools in nanomedicine. The main goals are to improve their stability in the biological environment, to mediate the bio-distribution of active compounds, improve drug loading, targeting, transport, release, and interaction with biological barriers. The cytotoxicity of nanoparticles or their degradation products remains a major problem, and improvements in biocompatibility obviously are a main concern of future research.
There are many technological challenges to be met, in developing the following techniques:
a) -Nano-drug delivery systems that deliver large but highly localized quantities of drugs to specific areas to be released in controlled ways;
b) -Controllable release profiles, especially for sensitive drugs;
c) -Materials for nanoparticles that are biocompatible and biodegradable;
d) -Architectures / structures, such as biomimetic polymers, nanotubes;
e) -Technologies for self-assembly;
f) Functions (active drug targeting, on-command delivery, intelligent drug release devices/ bioresponsive triggered systems, self-regulated delivery systems, systems interacting with the body, smart delivery);
g) -Virus-like systems for intracellular delivery;
h) -Nanoparticles to improve devices such as implantable devices/nanochips for nanoparticle release, or multi reservoir drug delivery-chips;
i) -Nanoparticles for tissue engineering; e.g. for the delivery of cytokines to control cellular growth and differentiation, and stimulate regeneration; or for coating implants with --nanoparticles in biodegradable polymer layers for sustained release;
j) -Advanced polymeric carriers for the delivery of therapeutic peptide/proteins (biopharmaceutics),
And also in the development of:
k) -Combined therapy and medical imaging, for example, nanoparticles for diagnosis and manipulation during surgery (e.g. thermotherapy with magnetic particles);
l) -Universal formulation schemes that can be used as intravenous, intramuscular or peroral drugs
m) -Cell and gene targeting systems.
n) -User-friendly lab-on-a-chip devices for point-of-care and disease prevention and control at home.
o) -Devices for detecting changes in magnetic or physical properties after specific binding of ligands on paramagnetic nanoparticles that can correlate with the amount of ligand.
-Better disease markers in terms of sensitivity and specificity.
Nanotechnologies and nanoparticles represent a promising and fast-growing field. This is principally because a nanodimensional substance can have physical and chemical properties that are different from those of the same substance with larger dimensions. Indeed, current technological developments in this field are attempting to take advantage of these unique properties.
The number and diversity of exposed workers will increase over the next few years. It is possible to introduce prevention and control measures promoting occupational health and safety at the very beginning of the conception and implementation stages of various processes.
Consequently, these measures, if taken right away, can constitute an important asset for the field of nanotechnology. However, a major challenge remains since current knowledge concerning health risks in this field is very fragmentary.
Certain nanotechnology applications will entail few new occupational health and safety risks. One such field is electronics, where miniaturization is advancing rapidly and is now being measured nanometrically. By contrast, free nanoparticles in the air are cause for concern due to their potentially negative impact on occupational health and safety, their accumulation in the environment and their enrichment via the food chain. These could have long-term risks for the health of populations. Although current knowledge on the toxicity of nanoparticles and the potential level of worker exposure is very limited, preliminary results in most of the important studies reveal significant biological activity and adverse effects.
In the short term, it will be almost impossible to acquire adequate knowledge of the risk associated with every type of nanoparticle. This is due not only to the proliferation of new nanoparticles but also to the modifications made to their surfaces; for these modifications greatly affect the surface properties of nanoparticles and possibly their biological reactivity and toxicity as well.
Given that it is currently impossible to carry out precise, quantitative risk assessment for every type of particle, it is important to develop a precautionary approach, using strategies based on prevention, sound practices and risk control that can inhibit the spread of occupational disease.
In the area of industrial hygiene, initiatives must be taken as soon as possible, using the best available measuring tools -- in spite of these tool’s limitations -- to estimate levels of occupational exposure. In view of the rapid advances in knowledge in occupational health and safety, it would seem important to update our assessment of knowledge in this field as soon as possible.
Thus nanoparticles provides many diseased as well as much more applications in world.
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