The particle size of drug nanocarriers dictates the fate of neurons; critical points in neurological therapeutics

Abstract

Neurological disorders and diseases are on the rise in the world, while pharmacists are being encouraged to encapsulate drugs into the nanocarriers. The critical key question is which size of nanocarrier has a promising neurotherapeutic effect. In the present study, FTY-720, an FDA approved drug, was encapsulated into O/W nanocarriers. SEM and DLS data indicated in ultrasonication and stirring methods resulted in spherical nanocarriers with a particle size of 60 and 195 nm (nF60 and nF195), respectively. Further to investigate the effect of particle size on neuronal cells, MTT assay, PI flow-cytometry, LDH release, and NO production examinations were performed. Results showed that small nanocarriers increased cell viability along with the decline of dead cells, while both nanocarriers decreased LDH release and NO production as compared to the conventional drug. Notably, qRT-PCR and western blotting data related to apoptotic markers indicated in the increase of cell mortality in cells treated by nF190 was not due to the increase of apoptosis and Bax/Bcl2 ratio. It is worth mentioning that integrin α5 as a cell surface receptor involves in neuritogenesis was over-expressed in neuronal cells treated by small nanocarriers. However, nF60 increased PTK2 over-expression along with neurite outgrowth, as well. In other words, nanocarriers at the size of 60 nm are preferred to 195 nm as a drug carrier in neurotherapy due to profound impacts on neural cells. Thanks to small nanocarrier broad positive action on neural viability and neurite outgrowth. The present study discloses a pharmaceutical strategy to design drugs based on their particle size efficiency.

Fingolimod Nanoemulsions at Different Particle Sizes Define the Fate of Spinal Cord Injury Recovery

“…Preparation of Fingolimod-Loaded Nanoemulsion. FTY720 nanocarriers at two different particle sizes with equal concentrations of FTY-720, oil, surfactant, and cosurfactant were prepared via low (stirring) and high-energy (probe ultrasound) emulsion oil in water (O/W) methods [18]. In brief, a mixture of 1 mg/ml fingolimod, 2% (w/w) mineral oil, 6% (w/w) Span 80-Tween 80 (surfactant), 1% (w/w) ethanol (cosurfactant), and distilled water was exposed to either a magnetic stirrer (800 rpm, 10 min) and/ or an ultrasound probe (400 W s −1 , 4 min) to obtain 190 nm and 65 nm oil-in-water (o/w) fingolimod nanoemulsions.…”

Particle Size of Drug Nanocarriers Defines the Fate of Spinal Cord Injury’s Recovery

“…Preparation of ngolimod-loaded nanoemulsion FTY720 nanocarriers at two different particle sizes with an equal concentration of FTY-720, oil, surfactant, and co-surfactant were prepared via a low (stirring) and high-energy (probe ultrasound) emulsion oil in water (O/W) methods 17 . In brief, the mixture of 1 mg/ml ngolimod, 2% (w/w) mineral oil, 6% (w/w) Span 80 -Tween 80 (surfactant), 1% (w/w) ethanol (co-surfactant), and distilled water were exposed to either magnetic stirrer (800 rpm, 10 min), and or ultrasound probe (400 W s −1 , 4min) to obtain 190 nm and 65nm Oil-in-water (o/w) ngolimod nanoemulsion.…”

Recent advances on drug delivery nanocarriers for cerebral disorders

“…It is worth noting that by changing the particle size and surface modification of nano preparations, not only the BBB permeability of numerous drugs can be improved, but also the therapeutic drugs will be transported into the targeted site or injured focus in the brain. The permeable efficiency of most drug delivery systems is mainly dependent on their particle size, as small nanoparticles are possessed of better fluidity, while contrarily those with large specific surface area will frequently improve intracellular uptake and biological distribution of drugs in brain tissue [31]. In addition to offering sustained release, improving the solubility of insoluble drugs and protecting drugs from being degraded by enzymes, nanotechnology and nanocarrier-based drug delivery systems should also play a specific therapeutic role on account of the characteristics of different brain diseases [32].…”