Nanocarrier has improved the drug action in pancreatic cancer

Hi all. As I told in my previous blog, this is the second post regarding my work that recently published. Pancreatic cancer is the most aggressive of all cancers. The five year survival rate of a patient is less than 6 %. Out of 100 persons diagnosed with pancreatic cancer 85 persons are mortal. For treating of such an aggressive disease "Gemcitabine" is recommended as the standard chemotherapy with 1000 mg/meter square. The poor bio-availability of the drug inside tumor environment and rapid efflux mechanisms of pancreatic cancer cells are the prime reasons for the pancreatic cancer resistance towards gemcitabine. To over come this drawback, a nanocarrier that is biocompatible and biodegradable with sustained drug release shall be effective in treating pancreatic cancer.

Cartoon depicting the Gemcitabine (Green) loaded PLGA (grey) nanospheres

Our work, published in Materials Science and Engineering: Chemistry, discussed about gemcitabine loaded poly(Lactide-co-glycolide) (PLGA) nanospheres as an effective treatment modality for pancreatic cancer. We have encapsulated the drug into PLGA nanospheres by water-oil-water emulsion method and achieved 15 % of encapsulation which is higher compared to existing literature, as it is tough to load a hydrophilic drug into a hydrophobic polymer. The gemcitabine was proved in the literature to be present in the polymer chain foldings and crevices formed by polymer chains inside the PLGA nanospheres. The drug loaded gemcitabine PLGA nanospheres provided a sustained drug release for 41 days. The nanospheres showed the bulk erosion degradation which enhances the release of drug in a sustained manner. The nanospheres were taken into cells by non-energy dependent mechanism. The specific targeting using an antibody will facilitate specific cancer cell attack by the nanocarrier.

Overall the biodegradable and biocompatible PLGA with gemcitabine loaded inside shall be a promising nanocarrier for pancreatic cancer treatment.

Reference

L.R.Jaidev, Uma Maheswari Krishnan, Swaminathan Sethuraman, (2015)  Gemcitabine loaded biodegradable PLGA nanospheres for in vitro pancreatic cancer therapy Material Science and Engineering:C , 47, 40–47.

http://www.sciencedirect.com/science/article/pii/S0928493114007280 

Sensitive detection of circulating tumor cells

Cirulating tumor cells are the prime things that detach from the solid tumor and reach the other parts of the body such as lungs, liver, spleen etc. Such a cancer state is called Metastasis which is an advanced state of the cancer. Some cancers like pancreatic cancer develop symptoms at this late stage. Hence the treatment is difficult and the patient survival rate is very low while the mortality rate is 85% (According to American cancer society statistics, 2013).

There is a clear need for the identification of these cells in the blood circulation so that the initiation of treatment methods to the patients will be easy for physicians. Currently we have several microfluidic based detection systems where these microfluidic chips will collect the cells and filter them. These cells will be cultured and identified. It is a very long and time consuming process. For a better detection system for identifying these circulating tumor cells, the device should be simple, sensitive and cost effective.

The recent paper published in Nature nanotechnology on 29 september 2013 developed a sensitive detection method to identify these circulating tumor cells. The authors/researchers from University of Michigan used the graphene oxide as the detection material for detecting the circulating tumor cells. The paper is very interesting and it mentioned the sensitivity of the fabricated device in detecting the circulating tumor cells such as PC-3, pancreatic cancer cells, MCF-7 and HS578T breast cancer cells.

The complete article will be obtained from  

http://www.nature.com/nnano/journal/v8/n10/abs/nnano.2013.194.html

Microparticles for brain drug delivery

The usage of nanoparticles for the therapeutic applications is in research for quite a long time. The fruits of the research are come out now. The clinical trails for various drug delivery formulations are in progress. The recent studies of the nanoformulations are well discussed in this article. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260950/


Eventhough we have many liposome formulations, the commercialization of polymer nanodrug formulations hasn't seen light yet. The recent study of pennstate university research group has showed the sustained release of the microparticles for brain drug delivery. The blood brain barrier is the primary limitation step for any drug to enter into brain. The liposomes are widely used for brain drug delivery as they are having the lipid component which can easily enter into the brain than other formulations. But the draw back of liposomes is the burst release of the drug. Most of the drug will be released within the short period of time. This causes the patient has to take more doses at regular periods of time.The pennstate research group led by Dr. Mohammad Reza Abidian, assistant professor of bioengineering, chemical engineering and materials science and engineering has mentioned that "Brain tumors are one of the world's deadliest diseases," which needs to be addressed with a potential carrier system. Their work has been recently reported in Science daily. In their words. "We are trying to develop a new method of drug delivery," said Abidian. "Not intravenous delivery, but localized directly into the tumor site."
Current treatment already includes leaving wafers infused with the anti-tumor agent BCNU in the brain after surgery, but when the drugs in these wafers run out, repeating invasive placement is not generally recommended.
"BCNU has a half life in the body of 15 minutes," said Abidian. "The drug needs protection because of the short half life. Encapsulation inside biodegradable polymers can solve that problem."

The research groups around the world are trying to have a suitable carrier system that can cure the brain cancer. The work done by pennstate university is one of the good work in a new approach. Hope new thinking in new ways provide the solution to the long suffering problem.

Courtesy: www.sciencedaily.com

Toxicological aspects of nanoparticles

Mr. Smith, stock broker for a famous firm, has interest in technology. So he always update his home electrical appliances and other gadgets regularly as there are no money constraints for him. Recently he purchased a new silver nanotechnology based washing machine. The sales person describe nanotechnology is the current highest technology which keeps the clothes away from bacteria and bad odour. A sales person knowing that much is good. He insisted on the beneficial part of nanoparticles and nanotechnology. Does he forget the other face of nanomaterials?! The toxic nature of nanoparticles, unfortunately, has become a major concern for environmentalists rather than general public. 

Do nanoparticles are toxic? Yes, nanoparticles are toxic but with high dosage concentrations. The study of nanoparticle toxicology is being carried out in many labs around the world and also publishing the results in many journals of various big publishers. The scientific community is concerned over the toxicity of the nanoparticles more than the policy makers and public. Nanoparticles are the smallest particles of metal or non metal or oxides etc., which are of the order thousand time lesser than micron size. Such small nanoparticles can reach to very end of the lungs, if inhaled, and very end of the blood vessels in the tissue if entered. Such a kind of particles are generally threat to the human body but thanks to god for giving such a strong immune system mechanism and defence processes, that the particles can be eliminated by RES system mostly, Urination etc. The problem comes when the dosage is high.

The high dosage of nanoparticles is toxic to cells which are the fundamental units of human body. The malfunction of a cell division leads to the generation of a bunch of immortal cells called as tumor and famous with the name "Cancer". Upto now we are talking about the toxicity of nanoparticles to healthy cells by dose dependent manner. Can't we use this aspect for the killling of cancer cells! A recent report in Nano Today authored by Stefan J. Soenen [1] reviewed the same aspect elaborately. The cancer cells are more prone to nanoparticle toxicity than the healthy cells which is an advantage to fight against cancer. The fluidity of the cancer cells enables the easy intake of nanoparticles which can act by two mechanisms. One way is to elicit the apoptosis pathway and the other one is the long term metal leaching. In the first mechanism, the nanoparticles are receptor mediated uptaken or by endocytosis stays for a long time inside the endosomes. The degeneration of the nanoparticles cause  pH changes in endosomes which then give signals to the nucleus to self destruct which is nothing but apoptosis. The other mechanism is the long term staying of the particle inside the cell and releasing the metal ions for a longer periods. These metal ions will be toxic to cells. It was proved that the metal ions alone given to cells are not affected than the cells given metal nanoparticles. The scientific understanding of the behaviour of nanoparticles toxicity to cells help in understanding the dose concentration and also the nanoparticle properties.

Toxicity studies of nanoparticles play a crucial role in understanding the demon of high dosage nanoparticles which can also become an angel in killing cancer cells. The two faces of nanoparticles is beneficial as per their application. The vibrant future of nanotechnology in providing the beneficial and commercial products is ahead.

[1]Stefaan J. Soenen, Jo Demeester, Stefaan C. De Smedt, Kevin Braeckmans. Turning a frown upside down: Exploiting nanoparticle toxicity for anticancer therapy.Nano Today (2013) 8, 121—125.