Development and Characterization of Core Shell Nanoparticle for Enhanced Drug Delivery to Treat Solid Tumor: Preparation and In-Vitro Assessment

Mortalities from cancer in the world are projected to continue rising, with an estimated 9 million and 11.4 million people dying from cancer in 2015 and 2030, respectively. Rates are rising as more people live to an old age and as mass lifestyle changes occur in the developing world. With present treating regimen for cancer, dose-limited toxicity is a big reason that reduces the efficacy of cancer treatments. In search for more effective cancer treatments, nanosized drug delivery systems, those are capable of delivering their drug payload selectively to cancer cells such as nanoparticles, solid lipid nanoparticles, liposomes are among the most promising approaches. Core shell nanoparticles are one of the investigated moieties in recent years that are seeking much attention nowadays for biomedical applications including the field of oncology.The present work aims at developing a core shell nanoparticle comprising Poly (D, L –lactide –co –glycolide) (PLGA) core and polyethyleneimine (PEI) shell loaded with anticancer bioactive docetaxel (DTX) for passive targeting of the tumor tissue. It is expected that incorporation of PEI will improve the uptake and subsequent release of the drug in the cytosol due to endosomal escape phenomenon. Keywords: Solid tumor; nanotechnology; nanoparticle; PLG

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Adenosine is a neuromodulator that operates via the most abundant inhibitory adenosine A1 receptors (A1Rs) and the less abundant, but widespread, facilitatory A2ARs. It is commonly assumed that A1Rs play a key role in neuroprotection since they decrease glutamate release and hyperpolarize neurons. In fact, A1R activation at the onset of neuronal injury attenuates brain damage, whereas its blockade exacerbates damage in adult animals. However, there is a down-regulation of central A1Rs in chronic noxious situations. In contrast, A2ARs are up-regulated in noxious brain conditions and their blockade confers robust brain neuroprotection in adult animals. The brain neuroprotective effect of A2AR antagonists is maintained in chronic noxious brain conditions without observable peripheral effects, thus justifying the interest of A2AR antagonists as novel protective agents in neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, ischemic brain damage and epilepsy. The greater interest of A2AR blockade compared to A1R activation does not mean that A1R activation is irrelevant for a neuroprotective strategy. In fact, it is proposed that coupling A2AR antagonists with strategies aimed at bursting the levels of extracellular adenosine (by inhibiting adenosine kinase) to activate A1Rs might constitute the more robust brain neuroprotective strategy based on the adenosine neuromodulatory system. This strategy should be useful in adult animals and especially in the elderly (where brain pathologies are prevalent) but is not valid for fetus or newborns where the impact of adenosine receptors on brain damage is different