Nanotechnology in Cancer Therapy : A Novel Drug Delivery

Thanks for your appreciation and compliment.

nice to have a good compliment from you...
Here is the reply for you...

High-resolution solution 1H NMR spectroscopy has been used to characterize the size of Pd dendrimer-encapsulated nanoparticles (DENs). The Pd nanoparticles measured by this technique contain 55, 147, 200, or 250 atoms, and they are encapsulated within sixth-generation, hydroxyl-terminated poly(amidoamine) PAMAM dendrimers (G6-OH). Detailed analysis of the NMR data shows that signals arising from the innermost protons of G6-OH(Pdn) decrease significantly as the size of the encapsulated nanoparticles increase. A mathematical correlation between this decrease in the integral value and the theoretical number of Pd atoms in the nanoparticle is extracted. It enables the elucidation of the size of Pd DENs by 1H NMR spectroscopy. NMR pulse-field gradient spin−echo experiments demonstrate that G6-OH with and without DENs have identical hydrodynamic radii, which excludes the presence of dendrimer/nanoparticle aggregates.

2.The structure of surface-immobilized peptides on gold nanoparticles has been described by solid-state 111Cd NMR .

3.The most important applications for the organic chemist are proton NMR and carbon-13 NMR spectroscopy. In principle, NMR is applicable to any nucleus possessing spin.

thankyou....
With Regards

please go through the following links as it is a deteailed information which cant be explained in short here in this column....

1.Drug delivery and targeting for pharmacists and pharmaceutical ... - Google Books Result:page 123 of this book contains the required information

http://books.google.co.in/books

2..Passive Targeting of Doxorubicin with Polymer Coated Liposomes in
Tumor: http://www.jstage.jst.go.jp/article/bpb/24/7/795/_pdf

This is for your detail information...

Thankyou....
With Regards....

when you see my presentation I mentioned about preventive measures to be taken to avoid cancer.Wright??
Now let me tell you about the use of nanotechnology in particular in prophylaxis of cancer...

1.To demonstrate the viability of the nanotechnology-based treatments, let us consider melanoma for example. Melanoma, a form of skin cancer, is caused primarily by ultraviolet radiation from the Sun .(The current method of preventive treatment against bombardment with this kind of harmful radiation involves suspending a substance that either absorbs or scatters ultraviolet radiation in a thick emulsion. We use this emulsion, called sunscreen, to coat our skin prior to prolonged exposure to sunlight.
Some of the problems with this method are that this emulsion can be easily rubbed off and can loose its effectiveness over time, thus needing to be reapplied periodically.
An even bigger problem is that we leave openings in the sunscreen coating during sunscreen application due to macro-scale and micro-scale imperfections in our skin.This allows the Ultra Violet (UV) radiation to permeate through the dead layer of skin,spreading out to a wider area due to slit diffraction and causing more widespread damage.
All of these problems take away from the overall effectiveness of this preventive method.
Some very recent works have shown that it is possible to tag specific types of cells with nanoparticles by conjugating them to targeting agents designed to recognise cell-specific surface proteins . Nanoparticles attached to desired
drugs or substances can be conjugated to short peptide chains, proteins or artificial nanobodies. If we manufacture nanoparticles attached to UV scattering substances like zinc oxide (ZnO) and titanium oxide (TiO2), or UV absorbing substances like octyl methoxycinnamate and oxybenzone , and specifically target these nanoparticles to skin cell surface proteins, we can effectively coat these cells with sunscreen on thenanoscale. With this nanotechnology-based preventive treatment method, we would effectively eliminate most of the problems mentioned above. If the cells can be coated
directly, the problem of diffraction in case where an area is sparsely coated will be eliminated.

Thankyou...
With Regards..

India has a good potential to market the nanoparticles...Yes...

"But to a much extent" is true only in the case of outsourcing market.
In India many companies carry out production of nanoparticle/ nano material formulations..in such a way we can say india has a good market in case of manufacturing them and selling them to out side countries.But when it comes to the use of such products in INDIA it is a bit less when compared to developed countries.

Thus we can say that INDIA has become a potential outsoucing market for the manufacturing & research on nanomaterials.

But it is a little bit expensive for the patient to use such products in INDIA as most of the cancer effected patients in india are below the poverty line...
The expensiveness of the product is due to the research work done..processing equipment used etc...

This can be minimised once the product is marketed world wide with easy methods of their production...

Hello Mr.Ramu....
Thankyou very much for your appreciation.

My Answer to the second question is

Yes nanometals show impact on normal cells while treating cancer...

A few examples are

1.Cytotoxicity and Genotoxicity of Silver Nanoparticles in Human Cells when the
Silver nanoparticles (Ag-np) are being used increasingly in wound dressings, catheters, and various household products due to their antimicrobial activity.

2.Cellular toxicity of various inhalable metal nanoparticles on human alveolar epithelial cells.

Nanoparticles (NPs) have a greater potential to travel through an organism via inhalation than any other larger particles, and could be more toxic due to their larger surface area and specific structural/chemical properties.

3.A number of pathological outcomes caused by the multiple pathways of injury induced by nanoparticles have been supported and limited experimental evidences are available that include inflammation, apoptosis, necrosis,fibrosis, hypertrophy, metaplasia and carcinogenesis.

4.Hazards associated with nanoparticles
a) Direct effects:
1.Cytotoxicity.
2. Pulmonary inflammation & pulmonary carcinogenicity.

b) Indirect effects
1. Alveolar inflammation.
2. Systemic hypercoagulability of blood, thereby increasing the risk of cardiovascular events
3.The disturbance of autonomic imbalance by nanoparticl having direct effect on heart & vascular function.

Instaed of all these hurdles , due a good amount of research these toxic side effects are minimised by correcting the cause for the effect.

Thankyou sir...
With Regards...

My answer to your question is......

A variety of ligands can be used in nanoparticles depending on the need...

a few examples are listed below

1.Surface modification of nanocrystalline metal oxide particles with enediol ligands increases site specific delivery in case of tumour thearapy.

2.Polydentate amino-functionalized poly(ethylene oxide)s with various block lengths are synthesized and used for ligand exchange and phase transfer of quantum dots and magnetic nanoparticles.The ligands enable the transfer of the previously water-insoluble particles into aqueous media.

3.Materials and methods are provided for making nanoparticles having a core including metal and/or semiconductor atoms,in which core is covalently linked to a plurality of ligands comprising a RNA ligand. The RNA ligands may include siRNA or miRNA.These nanoparticles are thus used in therapy and diagnosis.

4.nanoparticles further comprises ligands which include carbohydrate groups which increases lipophilicity of drug and targeted drug delivery is acheived.

5.Metallic core is an alloy selected from Au/Ag, Au/Cu, Au/Ag/Cu, Au/Pt, Au/Pd, Au/Ag/Cu/Pd, Au/Fe, Au/Cu, Au/Gd, Au/Fe/Cu, Au/Fe/Gd or Au/Fe/Cu/Gd , with the use of these a complex is formed between the surface antigen proteins and the metals. Thus the disease is treated.Usad in tumor therapy.

6. A ligand may be also a glycolipid or a glycoprotein.

7.ligands comprise DNA or RNA which are tagged to nanoparticles to achieve targeted delivery.

8.commonly used ligands are polyethylene glycol, ene diol in case of targeted drug delivery.

Thankyou very much sir...
With Regards...

It is really nice to have a good compliment from you...
My reply to your question is...

Regulatory bodies such as the United States Environmental Protection Agency and the Food and Drug Administration in the U.S. or the Health & Consumer Protection Directorate of the European Commission have started dealing with the potential risks posed by nanoparticles. So far, neither engineered nanoparticles nor the products and materials that contain them are subject to any special regulation regarding production, handling or labelling.

The European Commission believes that the benefits of nanotechnology will outweigh the potential risks, but stresses that today, there are no identified risks of nanoparticles, only identified hazards.’

The companies are using engineering control in production which protects the products from contamination as well as the workers from the products. When the workers are handling the nanoparticles they apply the personal protective equipment normal for a chemical or dusty working environment like masks and gloves. However, today nanoparticles are often treated as dust in terms of precautionary measures, but the question is whether the precautionary measures applied by the producers need to take the uncertainties into account and address nanoparticles as in a worst case-scenario.
There are limited precautionary measures taken to protect public health and the environment from exposure to nanoparticles. Precautionary measures for these purposes seem today to have a very low priority.

The European Commission has a duplex role as they are both promoting nanotechnology, but at the same time has a legal obligation to protect the citizens and the environment. The EC is not taking any precautions of today and it is likely that questions of precautionary measures will be left fully to the individual member states. However, no direct precautionary measures have been taken by the occupational health authorities, but some countries like the UK are more active than other countries and have already established working groups and contact networks covering both industry and scientists on this issue.

some of the regulatory bodies supervising this are...
1.health and safety executive(HSE)
2.Health and safety laboratory(HSL),USA
3.SCENIHR:Scientific cdommite on emerging and newly identified health risks...
4.RS-RAE:Royal society and Royal Academy of Engineers...

Source of my information:http://books.google.com/nanoparticles.

4Q.out of nanocapsules&nanospheres wich one offer zero order release?

Ans:
1.nanospheres used for sustained release ,given by I.V. infusion follow zero order release whoose rate is independent of initial concentration.

example:zero-order release of basic fibroblast growth factor from heparin- conjugated poly(L-lactide-co-glycolide) nanospheres.

2.Even nanocapsule formulations are designed in such a way that they show zero order release.

Example is Slow release testosterone-loaded nanocapsules in alginate, biodegradable hydropolymer, were prepared by in situ nanoemulsion-polymer crosslinking approach.Sustained diffusive drug release was observed in vitro, following zero order kinetics releasing the drug payload over a period of 48 hours. Embedding testosterone in alginate provided sustained release.

Thankyou sir...
With regards..

2Q.the decomposed products of biodegradable polemers employed for the production of nanoparticles or safe or not?

Ans:
Several different types of biodegradable biopolymers used are e.g. gelatin, albumin ,casein ,polysaccharides ,lecitins & synthetic polymers as polycynoacrylate , polyesters , polyanhydride ,polycaprolactone....These have been used to formulate sustain release nanoparticles...

yes the use of biodegradable nanoparticles is safe when compared to the use of non biodegradable nanoparicles....
Ex..Biodegradable polymeric nanoparticles designed for pulmonary drug delivery may not induce the same inflammatory response as non-biodegradable polystyrene particles of comparable size.
(source of my information:http://www.nanowerk.com/)

toxicity with their use is very rare except in case of repeated multiple dosages, which however can be cured & minimised.

2.chitosan is not rejected by the body and so it can improve the effective and safe delivery of drugs and vaccines with its absorptive power.

3.Biodegradable Nanoparticles Improve Oral Bioavailability of Amphotericin B[ an effective antifungal and antileishmanial agent] and Show Reduced Nephrotoxicity Compared to Intravenous Fungizone drug.

1.loading of nanoparticles??

Ans:
Preparation of Nanoparticles:
The different methods for preparing nanoparticles and for entrapping or adsorbing the drugs or antigens are:
1.reverse microemulsion polymerization process.
2.Interfacial polymerization.
3.Denaturation of natural macromolecules in an oil emulsion.
4.Desolvation of macromolecules.
5.Solvent displacement method.
6.A method of producing nanoparticles of size less than 100 nm using stirred media mill.
7.Emulsion polymerize method.
8.some other methods...

Q3.can we use vectors to improve the targeting potential of nanoparticles???

Ans:

yes sir..we can definitely use vectors to improve the potentional of nanoparticles in targetted delivery.....

some of the examples of the vectors used are..

protein conjugated liposomes have attracted a great deal of interest, principally because of their potential use as targeted drug delivery systems.

1.proteins,peptides,and small molecules as the vitamin folate ,which was used to target folate receptor overlapping tumour cells.

2.other examples include proteins such as Staphylococcus aureus protein A, plant lectins & enzymes.

However, the most commonly conjugated proteins are antibodies that lead to the denomination of immunoliposomes.

3.With respect to brain drug delivery vectors, modified proteins are used that undergo absorptive mediated transcytosis through the BBB.

Examples of brain targeting vectors include... Catioised albumin,the OX26 monoclonal antibody to the rat transferin receptor, or monoclonal antibodies to the insulin receptor.

Sir, my Answer to the question is....

A wide variety of cancers can be cured using nanotechnology....
Different novel carriers are used to deliver the medicament to the specific target site/organ.
But while treating the cancer the anatomy of the cancer effected organ is completely studied & a few modifications are to be made in the size and composition of the nanoparticles depending upon the type of the organ effected , for effective therapy.

A few examples are....

1. Nanotechnology has been used to create new and improved imaging techniques to find small tumors. Researchers have shown that incredibly small iron oxide particles (nanoparticulates) can be used with magnetic resonance imaging (MRI) to accurately detect cancers that have spread to lymph nodes, without requiring surgery.

2. Nanoscale delivery devices are being developed to deliver anticancer therapeutics specifically to tumors. Liposomes are one such "first generation" nanoscale device. Liposomal doxorubicin is used to treat specific forms of cancer, while liposomal amphotericin B treats fungal infections often associated with aggressive anticancer treatment. Recently, a nanoparticulate formulation of the well-known anticancer compound taxol was submitted as a new treatment for advanced stage breast cancer.

Thus finally what I would like to say is allmost all types of cancer can be treated by using nanotechnology because of its site specific delivery...with a few modifications to be made in the size and composition of the nanoparticles...

Thankyou very much sir....

Nanotechnology Enhances Fingerprint Detection:

Nanotechnology has enabled scientists to more reliably detect hidden fingerprints by using Nanoparticles as part of the process. The use of Nanoparticles in the field of fingerprint detection is nothing new. However, the current process is unstable and error prone. By contrast, current discoveries improve upon existing Nanotechnology research in the field of finger print detection to provide more reliable and consistent results each time the procedure is applied.

In both cases, Nanoparticles are used as the tracing mechanism for the fingerprint, but the critical difference has to do with the type of compound that is combined with the Nanoparticles to produce the outline of the final print. Prior to the current breakthrough, Nanoparticles were combined with citrate ions in a watery mixture to provide the catalyst for the fingerprint tracing. The gold Nanoparticles stuck to molecules with a positive charge in the finger print, and the final print was combined with silver ions which produced a chemical reaction that revealed the fingerprint. The problem with the current technique is that there is latent instability in the gold solution, making it difficult to reproduce the same results from one trial to the next.

The improved process uses a more stable solution with gold Nanoparticles containing extensive hydrocarbon chains dipped in an ether of petrol. This combination enables the solution to adhere to the fingerprint using hydrophobic interactions, with silver ions used to develop the prints as before. This improved process is significantly more reliable and faster than the current one, producing quality prints in as little as three minutes.

Research continues in using Nanoparticles to detect fingerprints in non-porous surfaces and in other aspects of forensic science. This makes it possible to unearth evidence that would otherwise remain invisible to the eye and to conventional methodologies used by specialists.

source of my information:http://www.nanotechnologydevelopment.com/
Thankyou...

Nanotechnology reveals fingerprints:

Hidden fingerprints can now be revealed quickly and reliably thanks to two developments in nanotechnology.
The current way of revealing hidden prints involves coating the marked surface with a watery suspension of gold nanoparticles, stabilised by citrate ions. Under acid conditions, the gold particles stick to the positively-charged molecules in the fingerprint. The print is then developed with a solution of silver ions, which undergo a chemical reaction to leave an outline of dark silver metal along the characteristic ridges of the fingerprint. But the gold solution is quite unstable, and the technique is difficult to reproduce from one test to another.

Now, Daniel Mandler, Joseph Almog and co-workers at The Hebrew University of Jerusalem, Israel, have replaced the traditional gold solution with a more stable equivalent. Their gold nanoparticles bristle with long hydrocarbon chains and are suspended in petrol ether. They stick to the fingerprint residues through hydrophobic interactions, and can be developed with silver as before, producing high quality prints after just three minutes immersion time .
The team has also developed a fingerprinting method for non-porous surfaces, using a petrol ether suspension of cadmium selenide/zinc sulphide nanoparticles stabilised by long chain amines. As with the team's gold solution, the nanoparticles adhere to the fingerprint by hydrophobic interactions. But in this case, as the nanoparticles fluoresce under UV light to reveal clear fluorescent prints, no additional developing stage is needed.
Claude Roux, director of the Centre for Forensic Science at the University of Technology, Sydney, Australia, said that the use of 'nanotechnology in the fingerprint community...can bring novel and practical solutions to develop and enhance latent fingermarks...that would otherwise remain un-detected.'
This view was confirmed by Antonio Cantu, an expert in forensic science for the United States Secret Service in Washington, who described the techniques as 'revolutionary' and said they 'are apt to greatly improve the recovery of latent prints on evidence'.

source of my information...www.nanowerk.com/news/newsid

sir I feel very glad in answering your questions sir......

5.The mechanism of medicament release from nanocapsule and nanosphere is same or different.

Answer:
yes it is different sir...

In Nano capsules the medicament is loaded in the shell of the capsule..so, once the capsule is digested the medicament is released and after dissolution it is absorbed into the body......

Where as in case of Nanosphere....

Intravenously injected into the patient, the nanospheres circulate through the bloodstream, where their surface proteins bind to the targeted toxins.They are acepted into cell by fusing with the cell surface....
The particle surfaces can be designed to provide receptor-mediated targeting of cells, sustained delivery, or magnetic targeting of organs. The nanospheres can deliver water-based or oil-based also.....

sir I feel very glad in answering your questions sir......

5.The mechanism of medicament release from nanocapsule and nanosphere is same or different.

Answer:
yes it is different sir...

In Nano capsules the medicament is loaded in the shell of the capsule..so, once the capsule is digested the medicament is released and after dissolution it is absorbed into the body......

Where as in case of Nanosphere....

Intravenously injected into the patient, the nanospheres circulate through the bloodstream, where their surface proteins bind to the targeted toxins.THey are acepted into cell by fusing with the cell surface....
The particle surfaces can be designed to provide receptor-mediated targeting of cells, sustained delivery, or magnetic targeting of organs. The nanospheres can deliver water-based or oil-based also.....

4Q:How medicament is loaded in to the nanoparticles?

Ans...medicaments are loaded into the liposomes by different methods like....
1.sonication method
2.Extrusion method
3.ion membrane gradient method....and a few more

3Q.How you justify the statement “nanotech based delivery is in expensive” as the materials employed and equipment used may be expensive and it needs highly expertized and more remunerated, skilled persons for their preparation.

Ans....Even though the production costs are more in nanotech based ....The safety and effective site specific delivery of medicament is high in case of nanoparticles with least side effects....
So, instead of wasting a lot of money and time with the conventional ..... the use of nanotech based reduces the cost and cures the disease in short duration of time...

Nanoscale devices may lead to detection of the earliest stages of cancer while simultaneously delivering anticancer agents to the tumor. nanoparticulate sensors can detect the cell that occurs when a cancer cell succumbs to the effects of an anticancer medicament. As a highly sensitive means of determining if a therapy is working, this application of nanotechnology could save a patient from months of ineffective medication and debilitating side effects, allowing a switch to a potentially more effective course of treatment.

2. Can we use same size nanoparticles having same composition to treat lung and liver cancers?

no sir....we cant use the same size And composition of nanoparticles to treat lung and liver cancers as the anatomy of both the organs is different....
One example is superparamagnetic iron oxide coated nanoparticles showed effective treatment in lung cancer butnot in liver cancer as the accumulation of ironoxide in liver is less....
so,the size of nanoparticles was a bit increased and the ironoxide composition was changed to show effective treatment in case of liver cancer

Thankyou sir...

sir I am very glad to answer your questions sir.....

Q: Can we use nanoparticles to treat cancer located outside the RES

Ans:.....In order to treat cancer located within the RES PEGylation of liposomes is necessary to protect them from phagocytosis by resident macrophages in order to increase the circulation time of the antitumour ....
But to treat cancer located outside RES chemiimmunoliposomes coated with PEG and tagged with a specific antibody against cancer antigen is used to acheive site specific delivery......

Thankyou sir

Thanx for your appreciation Ms.vishnupriya....

now let me give you the details you needed....
methods of preparing nanoparticle liposomes is by
1.sonicating method
2.ion membrane gradient method
3.extrusion method

Please go through the following link for the elaborate information you needeed...

see page 195 of the following book....
1. http://books.google.co.in/books?id=KdisZgkhjrUC&pg=PA195&dq=sonicating+m...

for the method of preparation of liposomes please go through
2. http://books.google.co.in/books?id=ClEJl4FIzrIC&pg=PA21&lpg=PA21&dq=load...

1) What the usage of cantilevers in detail ? Can any thing able to replace cantilevers ? If not why ?
2)Among metal, semicoductor, super paramagnetic nano particle which one are more effective ? why ?

Hello Mr.Dixon.....

YES....As you said I just gave an overview about the causes of cancer in my presentation as it is a huge topic to be discussed if started & also by now most of the people are aware of it...so I made it like that....

Now let me give you the details you needed....

External factors causing cancer are:
•Tobacco
•Infectious organisms
•Radiation
•Chemicals
Internal factors causing cancer are:

•Hormone
•Inherited mutations
•Immune conditions
•Mutations that occur from metabolism

please go through the following links for the information you needed...
1. http://www.healthizen.com/health-articles
2. http://en.wikipedia.org/wiki/Cancer
3. http://www.helium.com/items/89405-exploring-the-main-causes-of-cancer

Thankyou....

The use of quantum dots in cancer is to diagnose it...
the procedure of using quantum dots is clearly explained in the presentation please go through it carefully...

Thankyou...

chemi immunoliposomes means as the name suggests....chemi means chemicals loaded in liposomes.... and immuno means these liposomes by carrying specific antibodies tagged to them act as immunity providers....thus they are called chemiimmunoliposomes...

Methods of loading liposomes are....please carefully go through my ppt..I have mentioned already about it...
Thank you...

Answer for your second qestion.....
how to evaluate and minimize potential risks of nanoparticles??

Please go through http://toxsci.oxfordjournals.org/cgi/content/full/89/1/42
as it is a huge topic to be explained here....