Advances in Targeted Drug Delivery Approaches for the Central Nervous System Tumors: The Inspiration of Nanobiotechnology

Abstract

At present, brain tumor is among the most challenging diseases to treat and the therapy is limited by the lack of effective methods to deliver anticancer agents across the blood-brain barrier (BBB). BBB is a selective barrier that separates the circulating blood from the brain extracellular fluid. In its neuroprotective function, BBB prevents the entry of toxins, as well as most of anticancer agents and is the main impediment for brain targeted drug delivery approaches. Nanotechnology-based delivery systems provide an attractive strategy to cross the BBB and reach the central nervous system (CNS). The incorporation of anticancer agents in various nanovehicles facilitates their delivery across the BBB. Moreover, a more powerful tool in brain tumor therapy has relied surface modifications of nanovehicles with specific ligands that can promote their passage through the BBB and favor the accumulation of the drug in CNS tumors. This review describes the physiological and anatomical features of the brain tumor and the BBB, and summarizes the recent advanced approaches to deliver anticancer drugs into brain tumor using nanobiotechnology-based drug carrier systems. The role of specific ligands in the design of functionalized nanovehicles for targeted delivery to brain tumor is reviewed. The current trends and future approaches in the CNS delivery of therapeutic molecules to tumors are also discussed.

Targeting Epigenetics Signaling with Curcumin: A Transformative Drug Lead in Treatment of Schizophrenia?

“…As an atypical antipsychotic, amisulpride treatment results in larger effect size than first and second generation of antipsychotics with efficacy equal to olanzapine and risperidone in large scale RCT in schizophrenia [63]. A recent meta-analysis of randomized controlled trials to compare 15 antipsychotic drugs versus placebo in acute treatment of schizophrenia showed that amilosulpride ranked second to clozapine in the efficacy measure of standardized mean differences with 95% credible intervals clozapine 0.88, 0.73-1.03; amilosulpride 0.66, 0.53-0.78.…”

“…On the other hand, amisulpride behaves as a selective antagonist at the serotonin-receptor subtype 7: (5HT-7) mediating its likely procognitive action [62]. The pharmacological profile of amisulpride raises the intriguing hypothesis whether complex interactions at the D2/D3 and 5-HT-7 receptors reflect altered expression of D2/ D3 and 5HT (7) genes because of potent HDAC inhibition.As an atypical antipsychotic, amisulpride treatment results in larger effect size than first and second generation of antipsychotics with efficacy equal to olanzapine and risperidone in large scale RCT in schizophrenia [63]. A recent meta-analysis of randomized controlled trials to compare 15 antipsychotic drugs versus placebo in acute treatment of schizophrenia showed that amilosulpride ranked second to clozapine in the efficacy measure of standardized mean differences with 95% credible intervals clozapine 0.88, 0.73-1.03; amilosulpride 0.66, 0.53-0.78.…”

Next generation drug delivery: circulatory cells-mediated nanotherapeutic approaches

“…Nanocarriers (NCs), such as liposomes, hydrogels, nanoparticles, micelles, fibers, and dendrimers, provide several advantages in delivery applications and have been extensively applied to enhance the therapeutic efficacy of drugs [1][2][3][4]. However, the major challenges in NC applications are to transport the therapeutics to the target site without significant degradation, avoid rapid phagocytic clearance, prolonging the circulation time, insufficient targeting, and limited ability to cross biological barriers such as the blood-brain barrier [1][2][3][4].…”

“…However, the major challenges in NC applications are to transport the therapeutics to the target site without significant degradation, avoid rapid phagocytic clearance, prolonging the circulation time, insufficient targeting, and limited ability to cross biological barriers such as the blood-brain barrier [1][2][3][4]. Thus, alternative drug delivery approaches are desirable.…”

The Significance of Nanomedicine in Brain-Targeted Drug Delivery: Crossing Blood-Brain Barriers

“…The failure of vast majority of novel and current experiential therapeutics to reach/target the brain at a reasonable effective dose remains a major challenge. Despite great stride in understanding of the brain biology, from cellular to behavioral levels, the advances in basic science have not yet been fully developed in an interdisciplinary way, and a definitive translation from bench to bedside is still uncertain [6]. The scope of current communication focuses current challenges in brain-drug delivery, and significance of nanomedicine in crossing BBB, their downside and future prospects are also discussed.…”