[18]
Nanoparticles can be used in combination therapy for decreasing antibiotic resistance or for their antimicrobial properties.[19][20][21] Nanoparticles might also used to circumvent multidrug resistance (MDR) mechanisms.[22]
Types of systems used
Two forms of nanomedicine that have already been tested in mice and are awaiting human trials that will be using gold nanoshells to help diagnose and treat cancer,[23] and using liposomes as vaccine adjuvants and as vehicles for drug transport.[24][25] Similarly, drug detoxification is also another application for nanomedicine which has shown promising results in rats.[26] Advances in Lipid nanotechnology was also instrumental in engineering medical nanodevices and novel drug delivery systems as well as in developing sensing applications.[27] Another example can be found in dendrimers and nanoporous materials. Another example is to use block co-polymers, which form micelles for drug encapsulation.[11]
Polymeric nano-particles are a competing technology to lipidic (based mainly on Phospholipids) nano-particles. There is an additional risk of toxicity associated with polymers not widely studied or understood. The major advantages of polymers is stability, lower cost and predictable characterisation. However, in the patient's body this very stability (slow degradation) is a negative factor. Phospholipids on the other hand are membrane lipids (already present in the body and surrounding each cell), have a GRAS (Generally Recognised As Safe) status from FDA and are derived from natural sources without any complex chemistry involved. They are not metabolised but rather absorbed by the body and the degradation products are themselves nutrients (fats or micronutrients).
Protein and peptides exert multiple biological actions in the human body and they have been identified as showing great promise for treatment of various diseases and disorders. These macromolecules are called biopharmaceuticals. Targeted and/or controlled delivery of these biopharmaceuticals using nanomaterials like nanoparticles and Dendrimers is an emerging field called nanobiopharmaceutics, and these products are called nanobiopharmaceuticals.
Another vision is based on small electromechanical systems; nanoelectromechanical systems are being investigated for the active release of drugs. Some potentially important applications include cancer treatment with iron nanoparticles or gold shells.Nanotechnology is also opening up new opportunities in implantable delivery systems, which are often preferable to the use of injectable drugs, because the latter frequently display first-order kinetics (the blood concentration goes up rapidly, but drops exponentially over time). This rapid rise may cause difficulties with toxicity, and drug efficacy can diminish as the drug concentration falls below the targeted range.
Applications
Some nanotechnology-based drugs that are commercially available or in human clinical trials include:
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Abraxane, approved by the U.S. Food and Drug Administration (FDA) to treat breast cancer,[28] non-small- cell lung cancer (NSCLC)[29] and pancreatic cancer,[30] is the nanoparticle albumin bound paclitaxel.
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Doxil was originally approved by the FDA for the use on HIV-related Kaposi's sarcoma. It is now being used to also treat ovarian cancer and multiple myeloma. The drug is encased in liposomes, which helps to extend the life of the drug that is being distributed. Liposomes are self-assembling, spherical, closed colloidal structures that are composed of lipid bilayers that surround an aqueous space. The liposomes also help to increase the functionality and it helps to decrease the damage that the drug does to the heart muscles specifically.[31]
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Onivyde, liposome encapsulated irinotecan to treat metastatic pancreatic cancer, was approved by FDA on October 2015. [32]
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C-dots (Cornell dots) are the smallest silica-based nanoparticles with the size <10 nm. The particles are infused with organic dye which will light up with fluorescence. Clinical trial is underway since 2011 to use the C-dots as diagnostic tool to assist surgeons to identify the location of tumor cells.[33]
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An early phase clinical trial using the platform of ‘Minicell’ nanoparticle for drug delivery have been tested on patients with advanced and untreatable cancer. Built from the membranes of mutant bacteria, the minicells were loaded with nanometers, the minicell is bigger than synthetic particles developed for drug delivery. The researchers indicated that this larger size gives the minicells a better profile in side-effects because the minicells will preferentially leak out of the porous blood vessels around the tumor cells and do not reach the liver, digestive system and skin. This Phase 1 clinical trial demonstrated that this treatment is well tolerated by the patients. As a platform technology, the minicell drug delivery system can be used to treat a number of different cancers with different anti-cancer drugs with the benefit of lower dose and less side-effects.[34][35]
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In 2014, a Phase 3 clinical trial for treating inflammation and pain after cataract surgery, and a Phase 2 trial for treating dry eye disease were initiated using nanoparticle loteprednol etabonate.[36] In 2015, the product, KPI-121 was found to produce statistically significant positive results for the post-surgery treatment.[37]
Cancer
A schematic illustration showing how nanoparticles or other cancer drugs might be used to treat cancer.
Existing and potential drug nanocarriers have been reviewed.[38][39][40][41]
Nanoparticles have high surface area to volume ratio. This allows for many functional groups to be attached to a nanoparticle, which can seek out and bind to certain tumor cells. Additionally, the small size of nanoparticles (10 to 100 nanometers), allows them to preferentially accumulate at tumor sites (because tumors lack an effective lymphatic drainage system).[42] Limitations to conventional cancer chemotherapy include drug resistance, lack of selectivity, and lack of solubility. Nanoparticles have the potential to overcome these problems.[43]
In [59][60] Potentially, these nanocomposites may be used as a novel, mechanically strong, light weight composite as bone implants.
For example, a flesh welder was demonstrated to fuse two pieces of chicken meat into a single piece using a suspension of gold-coated nanoshells activated by an infrared laser. This could be used to weld arteries during surgery.[61] Another example is nanonephrology, the use of nanomedicine on the kidney.
Medical devices
Neuro-electronic interfacing is a visionary goal dealing with the construction of nanodevices that will permit computers to be joined and linked to the nervous system. This idea requires the building of a molecular structure that will permit control and detection of nerve impulses by an external computer. A refuelable strategy implies energy is refilled continuously or periodically with external sonic, chemical, tethered, magnetic, or biological electrical sources, while a nonrefuelable strategy implies that all power is drawn from internal energy storage which would stop when all energy is drained. A nanoscale enzymatic biofuel cell for self-powered nanodevices have been developed that uses glucose from biofluids including human blood and watermelons.[62] One limitation to this innovation is the fact that electrical interference or leakage or overheating from power consumption is possible. The wiring of the structure is extremely difficult because they must be positioned precisely in the nervous system. The structures that will provide the interface must also be compatible with the body's immune system.[63]
Molecular nanotechnology is a speculative subfield of nanotechnology regarding the possibility of engineering molecular assemblers, machines which could re-order matter at a molecular or atomic scale. Nanomedicine would make use of these nanorobots, introduced into the body, to repair or detect damages and infections. Molecular nanotechnology is highly theoretical, seeking to anticipate what inventions nanotechnology might yield and to propose an agenda for future inquiry. The proposed elements of molecular nanotechnology, such as molecular assemblers and nanorobots are far beyond current capabilities.[1][63][64][65]
See also
References
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Further reading