I am using a drug to reduce a neurodegenerative condition, a drug which is 40% lipid soluble and 60% water soluble so I want to synthesize biodegradable nanoparticles to attach the drug across the blood brain barrier and to increase the bioavailability in the brain.
Next to this, I have a plan to administrate this intranasally due the advantage of bypassing the blood brain barrier and to direct drug delivery to brain.
I have gone through some papers that say to use particle size below 5 microns because it is inhaled and directly sent to the lungs.
i) Should I administer nanoparticles intranasally?
ii) What should the size of the particles be?
How should particle size be administered intravenously?
Which is the best method for increasing the bioavailability of drug into the brain whether particle size 100-200 nm intravenously, or particle size more than 5 microns intranasally to rats?
Thanks in advance for your valuable suggestions and spending your valuable time.
Nanotechnology is being used to target brain. But toxicity studies are to be made very extinsively before any trial.
But in Ayurveda use of nano particles has been in use since ages, Gold & Silver Bhasm etc are the example.
Dear Sakthivel,
Although there are many publications (and even books; for example by Jorg Kreuter) that claim good results with drug delivery to the brain by means of nanoparticles, I think that this is a subject that needs more investigations. I think that currently there are some problems to be addressed regarding this issue:
1) most scientists, I think, are more likely to publish positive and successful results that support their thesis and usually miss to comment on existing problems. In this case, as prof. Sharma says, problems are usually related to toxicity, which indeed must be very extensively studied before ant further trials.
2) Smaller particles, 100-200 nm in size, administered i.v. is probably the better choice. Larger particles are usually very rapidly recognized by phagocytic cells in the blood (neutrophils) and macrophages in the tissues. Even the smaller particles are recognized by phagocytes quite easily if not suitably coated with hydrophilic shell.
3) the material that you choose must be biodegradable and the products of its degradation must be also non-toxic.
4) usually, NPs intended for drug delivery to the brain should be modified by apolipoproteins in order to be endocytosed by endothelial cells in brain capillaries (and transported via transcytosis through these cells). Since many types of nanoparticles cause oxidative stress in cells after endocytosis, one must keep attention on possible toxicity toward the endothelial cells in brain capillaries.
5) toxicity against neurons, which are quite sensitive cells, should be tested. The blood-brain barrier actually exists to protect neurons from numerous compounds that would otherwise damage neurons.
6) you should take into account that in the brain there is the so-called microglia, glial cells that are the resident macrophages of the brain and these cells can endocytose your NPs. Of course, this could diminish the effect of your drug targeting strategy, but also could lead to microglial toxicity, again by means of oxidative stress.
Probably, there are also other limitations and sources of possible problems, so it is better to get deeper in the matter before performing any time- and money-consuming experiments.
Kind regards,
GY
Thank you so much Georgi for your great suggestions. I am going to use Liposome Nanoparticle to target the brain. although i am not targeting any particular region in brain my purpose cross the blood brain barrier, liposome is biodegradable it won't accumulate in the brain and non toxic to the brain.
my another clarification is 100-200nm nanoparticle size will able to administrate through intranasally? some studies shows that when you administrate below 5 microns intranasally it will go to lungs.
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