Ischemic
stroke involves pro-inflammatory species, which implicates
inflammation in the disease mechanism. Recent studies indicate that
the prevalence of therapeutic choice such as stem cell transplantation
has seen an upsurge in ischemic stroke. However, after transplantation
the fate of transplanted cells is largely unknown. Human mesenchymal
stem cells (MSCs), due to their robust survival rate upon transplantation
in brain tissue, are being widely employed to treat ischemic stroke.
In the present study, we have evaluated naringenin-loaded gelatin-coated
polycaprolactone nanoparticles (nar-gel-c-PCL NPs) to rescue MSCs
against oxygen glucose deprived insult. Naringenin, due to its strong
anti-inflammatory effects, remains a therapeutic choice in neurological
disorders. Though, the low solubility and inefficient delivery remain
challenges in using naringenin as a therapeutic drug. The present
study showed that inflammation occurred in MSCs during their treatment
with oxygen glucose deprivation (OGD) and was well overturned by treatment
with nar-gel-c-PCL NPs. In brief, the results indicated that nar-gel-c-PCL
NPs were able to protect the loss of cell membrane integrity and restored
neuronal morphology. Then nar-gel-c-PCL NPs successfully protected
the human MSCs against OGD-induced inflammation as evident by reduced
level of pro-inflammatory cytokine (TNF-α, IFN-γ, and
IL-1β) and other inflammatory biomarkers (COX2, iNOS, and MPO
activity). Therefore, the modulation of inflammation by treatment
with nar-gel-c-PCL NPs in MSCs could provide a novel strategy to improve
MSC-based therapy, and thus, our nanoformulation may find a wide therapeutic
application in ischemic stroke and other neuro-inflammatory diseases.
With the increase in the expectancy of the life span of humans, neurodegenerative diseases (NDs) have imposed a considerable burden on the family, society, and nation. In defiance of the breakthroughs in the knowledge of the pathogenesis and underlying mechanisms of various NDs, very little success has been achieved in developing effective therapies. This review draws a bead on the availability of the nutraceuticals to date for various NDs (Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, Huntington’s disease, vascular cognitive impairment, Prion disease, Spinocerebellar ataxia, Spinal muscular atrophy, Frontotemporal dementia, and Pick’s disease) focusing on their various mechanisms of action in various in vivo and in vitro models of NDs. This review is distinctive in its compilation to critically review preclinical and clinical studies of the maximum phytochemicals in amelioration and prevention of almost all kinds of neurodegenerative diseases and address their possible mechanism of action. PubMed, Embase, and Cochrane Library searches were used for preclinical studies, while ClinicalTrials.gov and PubMed were searched for clinical updates. The results from preclinical studies demonstrate the efficacious effects of the phytochemicals in various NDs while clinical reports showing mixed results with promise for phytochemical use as an adjunct to the conventional treatment in various NDs. These studies together suggest that phytochemicals can significantly act upon different mechanisms of disease such as oxidative stress, inflammation, apoptotic pathways, and gene regulation. However, further clinical studies are needed that should include the appropriate biomarkers of NDs and the effect of phytochemicals on them as well as targeting the appropriate population.
The movement of micro and macro molecules into and within a cell significantly governs several of their pharmacokinetic and pharmacodynamic parameters, thus regulating the cellular response to exogenous and endogenous stimuli. Trafficking of various pharmacological agents and other bioactive molecules throughout and within the cell is necessary for the fidelity of the cells but has been poorly investigated. Novel strategies against cancer and microbial infections need a deeper understanding of membrane as well as subcellular trafficking pathways and essentially regulate several aspects of the initiation and spread of anti-microbial and anti-cancer drug resistance. Furthermore, in order to avail the maximum possible bioavailability and therapeutic efficacy and to restrict the unwanted toxicity of pharmacological bioactives, these sometimes need to be functionalized with targeting ligands to regulate the subcellular trafficking and to enhance the localization. In the recent past the scenario drug targeting has primarily focused on targeting tissue components and cell vicinities, however, it is the membranous and subcellular trafficking system that directs the molecules to plausible locations. The effectiveness of the delivery platforms largely depends on their physicochemical nature, intracellular barriers, and biodistribution of the drugs, pharmacokinetics and pharmacodynamic paradigms. Most subcellular organelles possess some peculiar characteristics by which membranous and subcellular targeting can be manipulated, such as negative transmembrane potential in mitochondria, intraluminal delta pH in a lysosome, and many others. Many specialized methods, which positively promote the subcellular targeting and restrict the off-targeting of the bioactive molecules, exist. Recent advancements in designing the carrier molecules enable the handling of membrane trafficking to facilitate the delivery of active compounds to subcellular localizations. This review aims to cover membrane trafficking pathways which promote the delivery of the active molecule in to the subcellular locations, the associated pathways of the subcellular drug delivery system, and the role of the carrier system in drug delivery techniques.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.