NANOPARTICLES IN THE DRUG DELIVERY

Abstract:
Nanomaterials are at the cutting edge of the rapidly developing area of nanotechnology. The potential for Nanoparticles in cancer drug delivery is infinite with novel new applications constantly being explored. Multifunctional Nanoparticles play a very significant role in cancer drug delivery. The promising implications of these platforms for advances in cancer diagnostics and therapeutics form the basis of this review.
The paper exhibits recent advances in cancer drug delivery. Cancer has a physiological barrier like vascular endothelial pores, heterogeneous blood supply, heterogeneous architecture etc. For a treatment to be successful, it is very important to get over these barriers. Nanoparticles have attracted the attention of scientists because of their multifunctional character. The treatment of cancer using targeted drug delivery Nanoparticles is the latest achievement in the medical field. Various Nanodevices can be used with out any side effects. They mainly include Cantilevers, Nanopores, Nanotubes, Quantum Dots (QDs), Nanoshells, Dendrimers and Biodegradable Hydrogels.

The paper mainly represents all the possible ways of treatment of cancer using various Nano devices.

Introduction to Nanoparticles:
A nanometer is one-billionth of a meter (10-9 m); a sheet of paper is about 100,000 nanometers thick. These nanoparticles give us the ability to see cells and molecules that we otherwise cannot detect through conventional imaging. The ability to pick up what happens in the cell, to monitor therapeutic intervention and to see when a cancer cell is mortally wounded or is actually activated is critical for the successful diagnosis and treatment of this disease.
For drug delivery in cancer we have “Nano scale devices”. Nanoscale devices are 102 to 104 times smaller than human cells but are similar in size to large biomolecules such as enzymes and receptors. Nanoscale devices smaller than 50 nm can easily enter most cells, and those smaller than 20 nm can move out of blood vessels as they circulate through the body. Nanodevices are suitable to serve as customized, targeted drug delivery vehicles to carry large doses of chemotherapeutic agents or therapeutic genes into malignant cells while sparing healthy cells.
Nanoscale constructs can serve as customizable, targeted drug delivery vehicles capable of ferrying large doses of chemotherapeutic agents or therapeutic genes into malignant cells while sparing healthy cells, greatly reducing or eliminating the often unpalatable side effects that accompany many current cancer therapies. Several nanotechnological approaches have been used to improve delivery of chemotherapeutic agents to cancer cells with the goal of minimizing toxic effects on healthy tissues while maintaining antitumor efficacy. Some nanoscale delivery devices, such as dendrimers, silica-coated micelles, ceramic nanoparticles, and cross linked liposomes can be targeted to cancer cells. These increase the selectivity of drugs towards cancer cells can and will reduce the toxicity to normal tissue.
Types of Nanoparticles
 Inorganic nanoparticles
 Organic nanoparticles

Liposomes, dendrimers, carbon nanotubes, emulsions, and other polymers are a large and well-established group of organic particles. Use of these organic nanoparticles has already produced exciting results. Liposomes are being used as vehicles for drug delivery in different human tumours, including breast cancer. Most inorganic nanoparticles share the same basic structure. This consists of a central core that defines the fluorescence, optical, magnetic, and electronic properties of the particle, with a protective organic coating on the surface. This outside layer protects the core from degradation in a physiologically aggressive environment and can form electrostatic or covalent bonds, or both, with positively charged agents and biomolecules that have basic functional groups such as amines and thiols. Several research groups have successfully linked fluorescent nanoparticles to peptides, proteins, and oligonucleotides.
Important characteristics
 Size
 Encapsulation Efficiency
 Zeta potential (surface charge)
 Release characteristics.
Types of Nanoparticles
 Multifunctional Nanoparticles
 Lipid/Polymer Nanoparticles
 Gold / Magnetic Nanoparticles
 Virus Based Nanoparticles
 Dry Powder Aerosol

Nanomedicine
One of the main goals of Nanomedicine is to create medically useful nanodevices that can function inside the body. Additionally, Nanomedicine will have an impact on the key challenges in cancer therapy such as localized drug delivery and specific targeting. Among the recently developed Nanomedicine and nanodevices, quantum dots, Nan wires, nanotubes, nanocantilevers, Nanopores, Nanoshells and nanoparticles are potentially the most useful for treating different types of cancer. Nanoparticles can be in the form of Nan spheres nanocapsules. Nanomedicines are a recent off-shoot of the application of nanotechnology to medical and pharmaceutical challenges, but have in fact been around for much longer in the guise of drug delivery systems. Nanomedicines that facilitate uptake and transport of therapeutically active molecules (‘delivery systems’) tend to be based on supramolecular assemblies of drug and functional carrier materials. The use of nanomedicines facilitates the creation of dose differentials between the site of the disease and the rest of the body, thus maximizing the therapeutic effect while minimizing non-specific side-effects.

Drug Delivery for Cancer Treatment
 Core features of cancer cell
 Abnormal growth control
 Improved cell survival
 Abnormal differentiation
 Unlimited replicated potential.
Transport of an anticancer drug in interestium will be governed by physiological and physiochemical properties of the interestium and by the physiochemical properties of molecules itself. Thus, to deliver therapeutic agents to tumour cells in vivo, one must overcome the following problems:
 Drug resistance at the tumour level due to physiological barriers
 Drug resistance at the cellular level
 Distribution, biotransformation and clearance of anticancer drugs in the body. Direct Introduction of anticancer drugs into tumour
 Injection Directly into the tumour
 Tumour necrosis therapy
 Injection into the arterial blood supply of cancer
 Local injection into the tumour for radiopotentiation
 Localized delivery of anticancer drugs by electroporation (Electro chemotherapy)
 Local delivery by anticancer drugs implants
Routes of Drug delivery
 Intraperitoneal
 Intrathecal
 Nasal
 Oral
 Pulmonary inhalation
 Subcutaneous injection or implant
 Transdermal drug delivery
 Vascular route: intravenous, intra-arterial
Systematic delivery targeted to tumour
 Heat-activated targeted drug delivery
 Tissue-selective drug delivery for cancer using carrier-mediated transport systems
 Tumour-activated prodrug therapy for targeted delivery of chemotherapy
 Pressure-induced filtration of drug across vessels to tumour
 Promoting selective permeation of the anticancer agent into the tumour
 Two-step targeting using biospecific antibody
 Site-specific delivery and light-activation of anticancer proteins

Drug delivery targeted to blood vessels of tumour
 Antiangiogenesis therapy
 Angiolytic therapy
 Drugs to induce clotting in blood vessels of tumour
 Vascular targeting agents
Special formulations and carriers of anticancer drugs
 Albumin based drug carriers
 Carbohydrate-enhanced chemotherapy
 Delivery of proteins and peptides for cancer therapy
 Fatty acids as targeting vectors linked to active drugs
 Microspheres
 Monoclonal antibodies
 Nanoparticles
 Paginated liposomes (enclosed in a polyethylene glycol belayed)
 Polyethylene glycol (PEG) technology
 Single-chain antigen-binding technology
Transmembrane drug delivery to intracellular targets
 Cytoporter
 Receptor-mediated endocytosis
 Transduction of proteins and Peptides
 Vitamins as carriers for anticancer agents
 Antisense therapy
 Cell therapy
 Gene therapy
 Genetically modified bacteria
 Oncolytic viruses
 RNA interference Biological Therapies
Pathways of Nanoparticles in Cancer drug delivery
Nanotechnology has tremendous potential to make an important contribution in cancer prevention, detection, diagnosis, imaging and treatment. It can target a tumor, carry imaging capability to document the presence of tumor, sense pathophysiological defects in tumor cells, deliver therapeutic genes or drugs based on tumor characteristics, respond to external triggers to release the agent and document the tumor response and identify residual tumor cells.
Nanoparticles are important because of their nanoscale structure but nanoparticles in cancer are still bigger than many anticancer drugs. Their “large” size can make it difficult for them to evade organs such as the liver, spleen, and lungs, which are constantly clearing foreign materials from the body. In addition, they must be able to take advantage of subtle differences in cells to distinguish between normal and cancerous tissues. Indeed, it is only recently that researchers have begun to successfully engineer nanoparticles that can effectively evade the immune system and actively target tumours. Active tumor targeting of nanoparticles involves attaching molecules, known collectively as ligands to the outsides of nanoparticles. These ligands are special in that they can recognize and bind to complementary molecules, or receptors, found on the surface of tumor cells. When such targeting molecules are added to a drug delivery Nanoparticles, more of the anticancer drug finds and enters the tumor cell, increasing the efficacy of the treatment and reducing toxic effects on surrounding normal tissues. Characteristic Nanoparticles Used for Drug Delivery in Cancer Treatment
Structure Size Role in drug delivery
Carbon magnetic Nanoparticles 40-50 nm For drug delivery and targeted cell destruction
Ceramics Nanoparticles 1-20 nm Holding therapeutics substances such as DNA in their cavities
Dendrimers ~ 35 nm Accumulate in the tumor tissue and allow the drug to act as sensitizer for photodynamics therapy without being released
Chitosan nanoparticles 110-180 nm
High encapsulation efficiency. In vitro release studies show a burst effect flowed by a slow and continuous release.
Liposomes 25-50 nm A new generation of liposomes that incorporate fullerenes to deliver drug that are not water soluble ,that tend to have large molecules
Low density lipoprotein 20-25 nm Drug solubilized in the lipid core or attached to the surface
Nanoemulsions 20-25 nm Drug in oil/or in liquid phases to improve absorption
Nanolipispheres 25-50 nm Carrier incorporation of lipophilic and hydrophilic drugs
Nanoparticles composites ~ 40 nm Attached to guiding molecules such as Mabs for targeted drug delivery
Nanoparticles 25-200 nm Act as continuous matrices containing dispersed or dissolved drug
Nanopill/micelle 20-45 nm Made for two polymer molecules-one water-repellent and the other hydrophobic that self assemble into a sphere called a micelle that can deliver drugs to specific structures within the cell
Nanospheres 50-500 nm Hollow ceramic Nanospheres created by ultrasound
Nanovesicles 25-3000 nm Single or multilamellar bilayer spheres containing the drugs in lipids
Polymer nanocapsules 50-200 nm Used for enclosing drugs
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The Role of Nanoparticles in Cancer Drug Delivery

Cancer disease challenging nanoparticles may be defined as being submicronic (< 1 µm) colloidal systems generally, but not necessarily, made of polymers (biodegradable or not). According to the process used for the preparation of the nanoparticles, Nanospheres or nanocapsules can be obtained. Unlike Nanospheres (matrix systems in which the drug is dispersed throughout the particles), nanocapsules are vesicular systems in which the drug is confined to an aqueous or oily cavity surrounded by a single polymeric membrane. Nanocapsules may, thus, be considered as a ‘reservoir’ system. If designed appropriately, it may act as a drug vehicle able to target tumor tissues or cells, to a certain extent, while protecting the drug from premature inactivation during its transport. Indeed, at the tumor level, the accumulation mechanism of intravenously injected nanoparticles relies on a passive diffusion or convection across the leaky, hyperpermeable tumor vasculature.
The uptake can also result from a specific recognition in the case of ligand decorated nanoparticles (‘active targeting’). Understanding and experience from other technologies such as Nanotechnology, Advanced Polymer Chemistry, and Electronic Engineering, are being brought together in developing novel methods of drug delivery. The current focus in development of cancer therapies is on targeted drug delivery to provide therapeutic concentrations of anticancer agents at the site of action and to spare the normal tissues. Cancer drug delivery is no longer simply packaging the drug in new formulations for unlike routes of delivery. Targeted drug delivery to tumours can increase the selectivity for killing cancer cells, decrease the peripheral/systemic toxicity and can permit a dose escalation. So targeted drug delivery will be more advantageous. These days drug delivery using micro/Nano particles have been shown to have great potentials for achieving controlled and targeted therapeutic effects.
The carrier particles have specific transportation and extravasation behaviours determined by their chemical structure, size, and surface properties etc. These characteristics are vital for the pharmacokinetics and pharmacodynamics of drugs being carried. To reach cancer cells in a tumor, a blood borne therapeutic molecule or cell must make its ways into the blood vessels of the tumor and across the vessel wall into interstitium, and finally migrate through the interstitium. For a molecule of given size, charge, and configuration, each of these transport processes may involve diffusion and convection. In the year 2002, there was a very fascinating article published in Science entitled “Nanoparticles Cut Tumours’ Supply Lines”.
In which, hungry tumours need new blood vessels for sustenance to deliver the goods. Cancer researchers have spent years working to starve tumours by blocking this blood vessel growth, or angiogenesis, with mixed success. The researchers packed a tiny particle with a gene that forces blood vessel cells to self-destruct, then they “mailed” the particle to blood vessels feeding tumours in mice. This is the latest achievement in the field of cancer treatment which is giving new hope for cancer patients who are suffering from angiogenesis. Targeted drug delivery is an invaluable need in pharmacology. Such an approach is particularly important in tumor therapy as the compounds are very toxic, and if they act on cells other than tumor cells, severe side effects are encountered. Any means that enables the increase of the ratio of the drug, which is delivered to the target site, will help to reduce such side effects.
Nanodevices: Detection and Cure

“Smart” dynamic nanoplatforms have the potential to change the way cancer is diagnosed, treated, and prevented. There are two basic approaches for creating nanodevices. Scientists refer to these methods as the top-down approach and the bottom-up approach. The top-down approach involves melding or etching materials into smaller components. This approach has traditionally been used in making parts for computers and electronics. The bottom-up approach involves assembling structures atom-by-atom or molecule-by-molecule, and may prove useful in manufacturing devices used in medicine. Most animal cells are 10,000 to 20,000 nanometers in diameter. This means that nanoscale devices (less than 100 nanometers) can enter cells and the organelles inside them can interact with DNA and proteins.
The nanodevices includes
 Cantilevers
 Nanopores
 Nanotubes
 Quantum Dots (QDs)
 Nanoshells
 Dendrimers
 Biodegradable Hydrogels
 Future Herbal Nanoparticles for Cancer
Tools developed through nanotechnology may be able to detect disease in a very small amount of cells or tissue. They may also be able to enter and monitor cells within a living body. In order to successfully detect cancer at its earliest stages; scientists must be able to detect molecular changes even when they occur only in a small percentage of cells. This means the necessary tools must be extremely sensitive. The potential for nanostructures to enter and analyse single cells suggests they could meet this need.

Conclusion

Nanotechnology is definitely a medical boon for diagnosis, treatment and prevention of cancer disease. It will radically change the way we diagnose, treat and prevent cancer to help meet the goal of eliminating suffering and death from cancer. Although most of the technologies described are promising and fit well with the current methods of treatment, there is still safety concerns associated with the introduction of Nanoparticles in the human body. These will require further studies before some of the products can be approved. The most promising methods of drug delivery in cancer will be those that combine diagnostics with treatment. These will enable personalized management of cancer and provide an integrated protocol for diagnosis and follow up that is so important in management of cancer patients. There are still many advances needed to improve Nanoparticles for treatment of cancers. Future efforts will focus on identifying the mechanism and location of action for the vector and determining the general applicability of the vector to treat all stages of tumours in preclinical models. Further studies are focused on expanding the selection of drugs to deliver novel Nanoparticles vectors. Hopefully, this will allow the development of innovative new strategies for cancer cures.