Todays, nano-pharmaceutics is emerging as an important field of science to develop and improve efficacy of different drugs. Although nutraceuticals are currently being utilized in the prevention and treatment of various chronic diseases such as cancers, a number of them have displayed issues associated with their solubility, bioavailability, and bio-degradability. In the present review, we focus on curcumin, an important and widely used polyphenol, with diverse pharmacological activities such as anti-inflammatory, anti-carcinogenic, anti-viral, etc. Notwithstanding, it also exhibits poor solubility and bioavailability that may compromise its clinical application to a great extent. Therefore, the manipulation and encapsulation of curcumin into a nanocarrier formulation can overcome these major drawbacks and potentially may lead to a far superior therapeutic efficacy. Among different types of nanocarriers, biological and biopolymer carriers have attracted a significant attention due to their pleiotropic features. Thus, in the present review, the potential protective and therapeutic applications of curcumin, as well as different types of bio-nanocarriers, which can be used to deliver curcumin effectively to the different target sites will be discussed.
Autophagy modulation is considered to be a promising programmed cell death mechanism to prevent and cure a great number of disorders and diseases. The crucial step in designing an effective therapeutic approach is to understand the correct and accurate causes of diseases and to understand whether autophagy plays a cytoprotective or cytotoxic/cytostatic role in the progression and prevention of disease. This knowledge will help scientists find approaches to manipulate tumor and pathologic cells in order to enhance cellular sensitivity to therapeutics and treat them. Although some conventional therapeutics suffer from poor solubility, bioavailability and controlled release mechanisms, it appears that novel nanoplatforms overcome these obstacles and have led to the design of a theranostic-controlled drug release system with high solubility and active targeting and stimuli-responsive potentials. In this review, we discuss autophagy modulators-related signaling pathways and some of the drug delivery strategies that have been applied to the field of therapeutic application of autophagy modulators. Moreover, we describe how therapeutics will target various steps of the autophagic machinery. Furthermore, nano drug delivery platforms for autophagy targeting and co-delivery of autophagy modulators with chemotherapeutics/siRNA, are also discussed.
Despite the numerous attempts in nerve tissue engineering, no ideal strategy has been translated into effective therapy for neuronal regeneration yet. Here, we designed a novel nerve regeneration scaffold combining aligned laminin-immobilized polyethersulfone (PES) nanofibers and human-induced pluripotent stem cells (hiPSCs) for transplantation strategies. Aligned and random PES nanofibers were fabricated by electrospinning method with a diameter of 95-500 nm and were then modified with covalent laminin bounding subsequent to O 2 plasma treatment. PES-functionalized fibers found to induce a remarkable higher rate of neuronal genes expression as compared to nontreated group. In addition, hiPSCs cultured on aligned pure fibers exhibited the extension of neurites along with fibers direction and an exponentially elevated expression of neuron specific enolase (early neuroectoderm marker), Tuj-1 (axonal marker), and microtubule-associated protein 2 (dendritic marker) in comparison with random pure fibers. The concomitant of increased hydrophilicity and biocompatibility along with exploiting topographical cues and directional guidance make aligned PES-plasma-laminin a versatile scaffold for adhesion, proliferation, spreading, and differentiation of hiPSCs into nerve cells.
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.
Spinal cord injury (SCI) is a debilitating condition for which no definitive treatment has yet been identified. Noteworthy, it influences other tissues through inflammatory reactions and metabolic disturbance. Therefore, fingolimod (FTY-720) as an FDA-approved inflammatory modulator would be promising. In the present study, nanocarriers at two distinct monodisperse particle sizes of 60 (nF60) and 190 (nF190) nm were prepared.The neural stem cell (NSC) viability and LDH release were studied in the face of the nanocarriers and free FTY-720. Results indicated that nanocarriers and free FTY-720 enhanced NSC viability than the control group.However, nF190 significantly induced less cell membrane damage than nF60. Nanocarriers and free FTY-720 enhanced motor neuron recovery in SCI rats, while body weight and return to bladder reflux by nF190 was significantly higher than nF60 groups. Return to bladder reflux might be due to the role of FTY-720 in regulation of detrusor muscle tone and preservation of the integrity of vessels by acting on endothelial cells. Moreover,nF190 gained higher soleus muscle weight than the free drugs;probably decreasing pro-inflammatory cytokines in soleus diminish muscular atrophy in SCI rats.To sum thing up, larger nanacarrirs with less cell membrane damage seems to be more efficient than smaller ones to manage SCI.
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