I have developed a nanoformulation for hepatic carcinoma. Now i'm going for cell line studies. I would like to know if the results of liver cancer cell line studies are enough or it is important to carry out in-vivo studies on rats.
I think that's more depends on your destination. Is it for master thesis or dissertation or business purpose maybe? And the range of impact factor of the journal you would like to publish at. And also the availability of facility and finance to complete such task.
I don't know what about in your country, but in here (Indonesia) for a master thesis, formulation and in vitro is considered sufficient. While adding more variable like in vivo testing would be enough for someone to get PhD.
As for the publication process, I think formulation of nanoparticle for cancer and in vitro test with cell lines would be enough to get you through a journal with impact factor 1-4, while adding in vivo could get you higher from 2.5. I'm not an expert, hope someone can correct me if I'm wrong.
Anyway, as from what I've seen in the field, people won't continue to in vivo test if the in vitro result is not promising. Unless they have a very good reason to do it. For example, for nanoparticle drug delivery case there is EPR (Enhanced Permeability & Retention) which help the nanoparticle to localize in cancer tissue, which might give different result compared to in vitro result (http://www.sciencedirect.com/science/article/pii/S0168365907006785). Well of course this EPR only work on nanoparticle within certain range of size, I forgot the exact number but I think it is around 100-200 nm.
Hi Brajesh I hope u must have prepared such formulation to target some pathway molecule...? in vitro methods are good to justify the mechanism of action of the formulation bz it is easy to take different controls. So far the mechanism is concern in vitro studies are ok. But in vivo system is quite complex bz lot of interactions of the formulations ...you may not get the same result....Stability of formulation, retention time, normal tissue toxicity and bioavailability are major problems....But definitely u go for in vivo bz the ultimately it has to work on in vivo system and some more modification may be needed keeping the the above problems in mind and without affecting the activity of formulation for which it is synthesized.
It is indeed important to conduct studies in a well defined system that consists of hepatocellular carcinoma cell lines in 2D.. To get a better idea of the effect of your nanoformulation, you can go for 3D cell culture drug screening, that way you are closer to knowing what really goes on in vivo .
However, in vitro studies conducted on your cell lines are not enough. Many drugs that work greatly on cancer cell lines in 2D cell culture fail to alleviate tumor burden when tested in mice models. Because of the fact that your study is centered at the nano-scale, it is crucial to conduct your studies in vivo since the naked drug or its nanoparticles might have the same effect when tested in cell lines in vitro, the real deal is to know if your nanoformulation enhances the potency of your drug in vivo by comparing it to control, and naked drug. Cancer cells undergo a process called angiogenesis by which de novo blood vessels are generated from pre-existing blood vessels. Generally, these blood vessels formed are leaky and not well structured because of the loose attachment of pericytes to them, which is why the nano-scale might be a better solution than delivering the naked drug alone because it can penetrate much easier to the tumor site. Also, nanoformulation of drugs is a great deal specifically when the drug turns out not to be much bioavailable or if it gets glucoconjugated then excreted by the urine. Hence, you might proceed with cell growth assays to determine if your nanoformulation and the naked drug inhibits proliferation of cancer cells, then you might want to characterize and elucidate the mechanisms induced by the drug, and finally, move to mice models whereby you really show how potent your nanoformulation is.
I think that's more depends on your destination. Is it for master thesis or dissertation or business purpose maybe? And the range of impact factor of the journal you would like to publish at. And also the availability of facility and finance to complete such task.
I don't know what about in your country, but in here (Indonesia) for a master thesis, formulation and in vitro is considered sufficient. While adding more variable like in vivo testing would be enough for someone to get PhD.
As for the publication process, I think formulation of nanoparticle for cancer and in vitro test with cell lines would be enough to get you through a journal with impact factor 1-4, while adding in vivo could get you higher from 2.5. I'm not an expert, hope someone can correct me if I'm wrong.
Anyway, as from what I've seen in the field, people won't continue to in vivo test if the in vitro result is not promising. Unless they have a very good reason to do it. For example, for nanoparticle drug delivery case there is EPR (Enhanced Permeability & Retention) which help the nanoparticle to localize in cancer tissue, which might give different result compared to in vitro result (http://www.sciencedirect.com/science/article/pii/S0168365907006785). Well of course this EPR only work on nanoparticle within certain range of size, I forgot the exact number but I think it is around 100-200 nm.
According to me Results from the Animal studies are more accurate, because there are many factor should take into consideration like (ADME). In vivo environment involves many enzymes, which affects the drug action. So better go for the animal studies once you find drug is active in cell lines.
it depends on your in vitro results. if you feel you have got potent activity, carry on with in vivo studies as it will give you a clear cut idea on how the drug acts and the influence of physiological conditions on the activity of drug. also go for estimation of proteins like MMP, VEGF and Topo isomerases for getting a better idea on the therapeutic efficacy of your drug. finally your paper gets enhanced if you incorporate in vivo studies.