ABSTRACT
The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s) may or may not be soluble in biological matrices, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglect able exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the Nano size also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation for the preparation of nanoparticles for drug delivery, varying from biological substances like albumin, gelatin and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles. It is obvious that the potential interaction with tissues and cells, and the potential toxicity, greatly depends on the actual composition of the nanoparticle formulation. This paper provides an overview on some of the currently used systems for drug delivery.
INTRODUCTION
Recent years have witnessed unprecedented growth of research and applications in the area of nanoscience and nanotechnology. There is increasing optimism that nanotechnology, as applied to medicine, will bring significant advances in the diagnosis and treatment of disease. Anticipated applications in medicine include drug delivery, both in vitro and in vivo diagnostics, nutraceuticals and production of improved biocompatible materials (Duncan 2003; De Jong et al 2005; ESF 2005; European Technology Platform on Nanomedicine 2005; Ferrari 2005). Engineered nanoparticles are an important tool to realize a number of these applications. It has to be recognized that not all particles used for medical purposes comply to the recently proposed and now generally accepted definition of a size ≤100 nm (The Royal Society and Royal Academy of Engineering 2004). However, this does not necessarily has an impact on their functionality in medical applications. The reason why these nanoparticles (NPs) are attractive for medical purposes is based on their important and unique features, such as their surface to mass ratio that is much larger than that of other particles, their quantum properties and their ability to adsorb and carry other compounds. NPs have a relatively large (functional) surface which is able to bind, adsorb and carry other compounds such as drugs, probes and proteins. However, many challenges must be overcome if the application of nanotechnology is to realize the anticipated improved understanding of the patho-physiological basis of disease, bring more sophisticated diagnostic opportunities, and yield improved therapies. Although the definition identifies nanoparticles as having dimensions below 0.1 μm or 100 nm, especially in the area of drug delivery relatively large (size >100 nm) nanoparticles may be needed for loading a sufficient amount of drug onto the particles. The composition of the engineered nanoparticles may vary. Source materials may be of biological origin like phospholipids, lipids, lactic acid, dextran, chitosan, or have more “chemical” characteristics like various polymers, carbon, silica, and metals. The interaction with cells for some of the biological components like phospholipids will be quite different compared to the non biological components such as metals like iron or cadmium. Especially in the area of engineered nanoparticles of polymer origin.
DEFINITION
A nanoparticle is a microscopic particle whose size is measured in nanometres (nm). It is defined as a particle with at least one dimension <200nm.or nanoparticles are solid colloidal particles ranging in size from 10nm to 1000nm. They consist of macromolecular materials in which the active principle is dissolved, entrapped or encapsulated, and/or to which the active principle is absorbed or attached.
Nanoparticle can be formulated, as injections consisting of spherical amorphous particles which do not aggregate, hence they can be safely administered by the intravenous route. Since no co-solvent is used to solubilize the drug, the overall toxicity of the formulation is decreased.
Nanoparticles represent very promising carrier system for the targeting of anti-cancer agents to tumors. Nanoparticles exhibit a significant tendency to accumulate in a number of tumors after iv injection. Nanoparticles can also be used in Brain Drug Targeting. Poly (butyl cyanoacrylate) nanoparticles represent the only nanoparticles that were so far successfully used for in vivo delivery of drugs to brain. This polymer has the advantage that it is very rapidly biodegradable. The first drug that was delivered to brain using nanoparticles was the Hex peptide Dalargin (Tyr-D-Ala-Gly-Phe-Leu-Arg), a Leu-enkephalin analouge with opioid activity. Other drugs that have successfully been transported into the brain are loperamide, tubocurarine, and doxorubicin. Nanoparticles mediated drug transport to the brain depends on the over coating of the particles with polysorbates, especially polysorbate 80.
Nanoclusters have at least one dimension between 1 and 10 nanometers and a narrow size distribution. Nano powders are agglomerates of ultrafine particles, nanoparticles, or nanoclusters. Nanometer-sized Single crystals or Single domain ultrafine particles, are often referred to as nanocrystals. Nanoparticle research is currently an area of intense scientific interest due to a wide variety of potential applications in biomedical, optical and electronic fields.
TYPES OF NANOPARTICLES
Nanoparticles can be classified into different types according to the size, morphology, physical and chemical properties. Some of them are carbon-based nanoparticles, ceramic nanoparticles, metal nanoparticles, semiconductor nanoparticles, polymeric nanoparticles and lipid-based nanoparticles.
CORBON-BASED NANOPARTICLES
Carbon-based nanoparticles include two main materials: carbon nanotubes (CNTs) and fullerenes. CNTs are nothing but graphene sheets rolled into a tube. These materials are mainly used for the structural reinforcement as they are 100 times stronger than steel.
CNTs can be classified into single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs). CNTs are unique in a way as they are thermally conductive along the length and non-conductive across the tube.
CERAMIC NANOPARTICLES
Ceramic nanoparticles are inorganic solids made up of oxides, carbides, carbonates and phosphates. These nanoparticles have high heat resistance and chemical inertness. They have applications in photocatalysis, photodegradation of dyes, drug delivery, and imaging.
METAL NANOPARTICLES
Metal nanoparticles are prepared from metal precursors. These nanoparticles can be synthesized by chemical, electrochemical, or photochemical methods. In chemical methods, the metal nanoparticles are obtained by reducing the metal-ion precursors in solution by chemical reducing agents. These have the ability to adsorb small molecules and have high surface energy.
SEMICONDUCTOR NANOPARTICLES
Semiconductor nanoparticles have properties like those of metals and non-metals. They are found in the periodic table in groups II-VI, III-V or IV-VI. These particles have wide bandgaps, which on tuning shows different properties. They are used in photocatalysis, electronics devices, photo-optics and water splitting applications.
POLYMERIC NANOPARTICLES
Polymeric nanoparticles are organic based nanoparticles. Depending upon the method of preparation, these have structures shaped like nanocapsular or nanospheres. A nanosphere particle has a matrix-like structure whereas the nanocapsular particle has core-shell morphology. In the former, the active compounds and the polymer are uniformly dispersed whereas in the latter the active compounds are confined and surrounded by a polymer shell.
LIPID-BASED NANOPARTICLES
Lipid nanoparticles are generally spherical in shape with a diameter ranging from 10 to 100nm. It consists of a solid core made of lipid and a matrix containing soluble lipophilic molecules. The external core of these nanoparticles is stabilized by surfactants and emulsifiers. These nanoparticles have application in the biomedical field as a drug carrier and delivery and RNA release in cancer therapy.