The design of a drug that successfully overcomes the constraints imposed by the blood−brain barrier (BBB, which acts as a gatekeeper to the entry of substances into the brain) requires an understanding of the biological firewall. It is also of utmost importance to understand the physicochemical properties of the said drug and how it engages the BBB to avoid undesired side effects. Since fewer than 5% of the tested molecules can pass through the BBB, drug development pertaining to brain-related disorders takes inordinately long to develop. Furthermore, in most cases it is also unsuccessful for allied reasons. Several drug delivery systems (DDSs) have shown excellent potential in drug delivery across the BBB while demonstrating minimal side effects. This mini-review summarizes key features of the BBB, recapitulates recent advances in our understanding of the BBB, and highlights existing strategies for the delivery of drug to the brain parenchyma.
While pharmaceutical drugs have revolutionized human life, there are several features that limit their full potential. This review draws attention to some of the obstacles currently facing the use of chemotherapeutic drugs including low solubility, poor bioavailability and high drug dose. Overcoming these issues will further enhance the applicability and potential of current drugs. An emerging technology that is geared towards improving overall therapeutic efficiency resides in drug delivery systems including the use of polymeric nanoparticles which have found widespread use in cancer therapeutics. These polymeric nanoparticles can provide targeted drug delivery, increase the circulation time in the body, reduce the therapeutic indices with minimal side-effects, and accumulate in cells without activating the mononuclear phagocyte system (MPS). Given the inroads made in the field of nanodelivery systems for pharmaceutical applications, it is of interest to review and emphasize the importance of Polymeric nanocarrier system for drug delivery in chemotherapy.
The recent advances in applications of nanotechnology including the use of inorganic, polymeric, magnetic and carbon nanomaterials in drug delivery for treatment of neurodegenerative diseases are reported.
Prion-like amyloids self-template and form toxic oligomers, protofibrils, and fibrils from their soluble monomers; a phenomenon that has been implicated in the onset and progress of neurodegenerative disorders such as Alzheimer's (AD), Parkinson's (PD), Huntington's, and systemic lysozyme amyloidosis. Carbon quantum dots (CQDs), sourced from Na−citrate as a carbon precursor were synthesized and characterized before being tested for their ability to intervene in amyloidogenic (fibrilforming) trajectories. Hen-egg white lysozyme (HEWL) served as a model amyloidogenic protein. A pulse-chase lysozyme fibrilforming assay developed to examine the impact of CQDs on the HEWL amyloid-fibril-forming trajectory used ThT fluorescence as a reporter of mature fibril presence. The results revealed that the Na−citrate-derived CQDs were able to intervene at multiple points along the fibril-forming trajectory by preventing the conversion of both monomeric and oligomeric HEWL intermediates into mature fibrils. In addition, and importantly, the carbon nano material (CNM) was able to dissolve oligomeric HEWL into monomeric HEWL and provoke the disaggregation of mature HEWL fibrils. These results suggest that Na−citrate CQD's intervene in amyloidogenesis by multiple mechanisms. The gathered data, coupled with cell-line results demonstrating the relatively low cytotoxicity of Na−citrate CQDs, suggest that this emerging CNM has the potential to intervene both prophylactically and therapeutically in protein misfolding diseases. The aforementioned findings are likely to enable Na−citrate CQDs to eventually transition to both cell-line and preclinical models of protein-misfolding-related disorders. Importantly, the study outcomes positions Na−citrate CQDs as an important class of chemical, nanotechnological, and biobased interventional tools in neuroscience.
Antioxidants derived
from nature, such as ellagic acid (EA), demonstrated
high potency to mitigate neuronal oxidative stress and related pathologies,
including Parkinson’s disease. However, the application of
EA is limited due to its toxicity at moderate doses and poor solubility,
cellular permeability, and bioavailability. Here, we introduce a sustainably
resourced, green nanoencasement strategy to overcome the limitations
of EA and derive synergistic effects to prevent oxidative stress in
neuronal cells. Chitosan, with its high biocompatibility, potential
antioxidant properties, and flexible surface chemistry, was chosen
as the primary component of the nanoencasement in which EA is immobilized.
Using a rotenone model to mimic intracellular oxidative stress, we
examined the effectiveness of EA and chitosan to limit cell death.
Our studies indicate a synergistic effect between EA and chitosan
in mitigating rotenone-induced reactive oxygen species death. Our
analysis suggests that chitosan encapsulation of EA reduces the inherent
cytotoxicity of the polyphenol (a known anticancer molecule). Furthermore,
its encapsulation permits its delivery via a rapid burst phase and
a relatively slow phase making the nanohybrid suitable for drug release
over extended time periods.
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