Protective effects of saffron and its active components against oxidative stress and apoptosis in endothelial cells.

In this study, we investigated the role of mitogen-activated protein kinase (MAPK) signaling pathways in mediation of the protective effects of saffron extract, saffron essential oil, safranal and crocin on bovine aortic endothelial cells against oxidative injury. The viability of cells in response to H2O2-induced toxicity (0.4, 2 and 10 mM) was measured using resazurin assay in the presence or absence of saffron extract (2-40 µg/ml), saffron oil (2-40 µg/ml), safranal (2-40 µM) and crocin (2-40 µM). Dichlorodihydrofluorescin diacetate was used as an indicator for the amount of reactive oxygen species (ROS) in cells at the same concentrations of samples as the former test. In addition, propidium iodide staining of the fragmented DNA was performed to measure the level of apoptotic cells by the application of 2-10 µM of crocin and safranal. Finally, the proteins involved in apoptosis were detected using western blotting at the concentration of 0, 2, 10 µM for crocin and safranal. The results indicated that all tested moieties improved viability and reduced ROS production in H2O2-treated cells (p < 0.001 compared to H2O2). In addition, a significant decrease in apoptosis (3-35%) was observed in the cells that were treated with crocin and safranal. The observed protective effects of crocin and safranal were associated with the activation of SAPK/JNK and inhibition of ERK ½ that are related to MAPK pathways. The antioxidant and anti-apoptotic activities of saffron and its ingredients in endothelial cells are mediated via MAPK signaling pathways and might be of therapeutic potential for endothelial dysfunctionalities.

Oligonucleotide based nanogels for cancer therapeutics.

Oligonucleotide-based nanogels, as nascent biomaterials, possess several unique functional, structural, and physicochemical features with excellent drug-loading capacity and high potential for cancer gene therapy. Ongoing studies utilizing oligonucleotide-based nanogels hold great promise, as these cutting-edge nanoplatforms can be elegantly developed with predesigned oligonucleotide sequences and complementary strands which are self-assembled or chemically crosslinked leading to the development of nanogels with predictable shape and tunable size with the desired functional properties. Current paper provides a summary of the properties, preparation methods, and applications of oligonucleotide-based nanogels in cancer therapy. The review is focused on both conventional and modified forms of oligonucleotide-based nanogels, including targeted nanogels, smart release nanogels (responsive to stimuli such as pH, temperature, and enzymes), as well as nanogels used for gene delivery. Their application in cancer immunotherapy and vaccination, photodynamic therapy, and diagnostic applications when combined with other nanoparticles is further discussed. Despite emerging designs in the development of oligonucleotide based nanogels, this field of study is still in its infancy, and clinical translation of these versatile nano-vehicles might face challenges. Hence, extensive research must be performed on in vivo behavior of such platforms determining their biodistribution, biological fate, and acute/subacute toxicity.

Therapeutic targeting of TGF-ß in lung cancer.

Transforming growth factor-ß (TGF-ß) plays a complex role in lung cancer pathophysiology, initially acting as a tumor suppressor by inhibiting early-stage tumor growth. However, its role evolves in the advanced stages of the disease, where it contributes to tumor progression not by directly promoting cell proliferation but by enhancing epithelial-mesenchymal transition (EMT) and creating a conducive tumor microenvironment. While EMT is typically associated with enhanced migratory and invasive capabilities rather than proliferation per se, TGF-ß's influence on this process facilitates the complex dynamics of tumor metastasis. Additionally, TGF-ß impacts the tumor microenvironment by interacting with immune cells, a process influenced by genetic and epigenetic changes within tumor cells. This interaction highlights its role in immune evasion and chemoresistance, further complicating lung cancer therapy. This review provides a critical overview of recent findings on TGF-ß's involvement in lung cancer, its contribution to chemoresistance, and its modulation of the immune response. Despite the considerable challenges encountered in clinical trials and the development of new treatments targeting the TGF-ß pathway, this review highlights the necessity for continued, in-depth investigation into the roles of TGF-ß. A deeper comprehension of these roles may lead to novel, targeted therapies for lung cancer. Despite the intricate behavior of TGF-ß signaling in tumors and previous challenges, further research could yield innovative treatment strategies.

Targeting fibroblast activation protein (FAP): advances in CAR-T cell, antibody, and vaccine in cancer immunotherapy.

Fibroblast activation protein (FAP) is a serine protease with dual enzymatic activities overexpressed in cancer-associated fibroblasts (CAFs) in several tumor types, while its expression in healthy adult tissues is scarce. FAP overexpression on CAFs is associated with poor prognosis and plays an important role in tumor development, progression, and invasion. Therefore, FAP is considered a robust therapeutic target for cancer therapy. Here, we try to review and highlight the recent advances in immunotherapies for FAP targeting including the anti-FAP antibodies and immunoconjugates, FAP chimeric antigen receptor (CAR)-T cell, and various FAP vaccines in a preclinical and clinical setting. Subsequently, a discussion on the challenges and prospects associated with the development and translation of effective and safe therapies for targeting and depletion of FAP is provided. We proposed that new CAR-T cell engineering strategies and nanotechnology-based systems as well as advanced functional biomaterials can be used to improve the efficiency and safety of CAR-T cells and vaccines against FAP for more personalized immunotherapy. This review emphasizes the immune targeting of FAP as an emerging stromal candidate and one of the crucial elements in immunotherapy and shows the potential for improvement of current cancer therapy. A summary of different immunotherapy approaches to target fibroblast activation protein (FAP) for cancer therapy.

Novel liposomal glatiramer acetate: Preparation and immunomodulatory evaluation in murine model of multiple sclerosis.

The frequent administration rate required for Glatiramer acetate (GA), a first-line therapy for Multiple sclerosis (MS), poses patient compliance issues. Only a small portion of the subcutaneously administered GA is available for phagocytosis by macrophages, as most of it is hydrolyzed at its administration site or excreted renally. To unravel these hurdles, we have prepared liposomal formulations of GA through thin film-hydration method plus extrusion. The clinical and histopathological efficacy of GA-loaded liposomes were assessed in prophylactic and therapeutic manners on murine model of MS (experimental autoimmune encephalomyelitis (EAE)). The selected GA liposomal formulation showed favorable size (275 nm on average), high loading efficiency, and high macrophage localization. Moreover, administration of GA-liposomes in mice robustly suppressed the inflammatory responses and decreased the inflammatory and demyelinated lesion regions in CNS compared to the free GA with subsequent reduction of the EAE clinical score. Our study indicated that liposomal GA could be served as a reliable nanomedicine-based platform to hopefully curb MS-related aberrant autoreactive immune responses with higher efficacy, longer duration of action, fewer administration frequencies, and higher delivery rate to macrophages. This platform has the potential to be introduced as a vaccine for MS after clinical translation and merits further investigations.

Poly-γ-glutamic acid nanoparticles as adjuvant and antigen carrier system for cancer vaccination.

Vaccination is an innovative strategy for cancer treatment by leveraging various components of the patients' immunity to boost an anti-tumor immune response. Rationally designed nanoparticles are well suited to maximize cancer vaccination by the inclusion of immune stimulatory adjuvants. Also, nanoparticles might control the pharmacokinetics and destination of the immune potentiating compounds. Poly-γ-glutamic acid (γ-PGA) based nanoparticles (NPs), which have a natural origin, can be easily taken up by dendritic cells (DCs), which leads to the secretion of cytokines which ameliorates the stimulation capacity of T cells. The intrinsic adjuvant properties and antigen carrier properties of γ-PGA NPs have been the focus of recent investigations as they can modulate the tumor microenvironment, can contribute to systemic anti-tumor immunity and subsequently inhibit tumor growth. This review provides a comprehensive overview on the potential of γ-PGA NPs as antigen carriers and/or adjuvants for anti-cancer vaccination.

Preparation of stable enteric folic acid-loaded microfiber using the electrospinning method.

Objectives: Folic acid is an essential vitamin, labile to hydrolysis in the acidic environment of the stomach with low water solubility and bioavailability. In order to solve these problems, enteric oral folic acid-loaded microfibers with a pH-sensitive polymer by electrospinning method were prepared. Materials and Methods: Electrospinning was performed at different folic acid ratios and voltages. Fibers were evaluated in terms of mechanical strength, acidic resistance, and drug release. Additionally, DSC (Differential Scanning Calorimetry), FTIR (Fourier-transform infrared spectroscopy), and XRD (X-ray diffraction) analyses were performed on the optimal formulation. Results: Drug ratio and voltage had a considerable effect on fibers' entrapment efficiency, acid resistance, and mechanical strength. Based on the obtained results, the optimum formulation containing 1.25% of the drug/polymer was prepared at 18 kV. The entrapment efficiency of the optimal sample was above 90% with an acid resistance of higher than 70%. The tensile test confirmed the high mechanical properties of the optimum microfiber. DSC and XRD tests indicated that folic acid was converted to an amorphous form in the fiber structure and the FTIR test confirmed the formation of a chemical bond between the drug and the polymer. The release of the drug from the optimal fiber was about 90% in 60 min. Conclusion: In conclusion, the optimal formulation of folic acid with proper mechanical properties can be used as a candidate dosage form for further bioavailability investigations.

Curcumin-based nanotechnology approaches and therapeutics in restoration of autoimmune diseases.

Autoimmune diseases usually arise as a result of an aberrant immune system attack on normal tissues of the body, which leads to a cascade of inflammatory reactions. The immune system employs different types of protective and anti-inflammatory cells for the regulation of this process. Curcumin is a known natural anti-inflammatory agent that inhibits pathological autoimmune processes by regulating inflammatory cytokines and their associated signaling pathways in immune cells. Due to the unstable nature of curcumin and its susceptibility to either degradation, or metabolism into other chemical entities (i.e., metabolites), encapsulation of this agent into various nanocarriers would appear to be an appropriate strategy for attaining greater beneficial effects from curcumin as it pertains to immunomodulation. Many studies have focused on the design and development of curcumin nanodelivery systems (micelles, dendrimers, and diverse nanocarriers) and are summarized in this review in order to obtain greater insight into novel drug delivery systems for curcumin and their suitability for the management of autoimmune diseases.

Recent advancements in nanoparticle-mediated approaches for restoration of multiple sclerosis.

Multiple Sclerosis (MS) is an autoimmune disease with complicated immunopathology which necessitates considering multifactorial aspects for its management. Nano-sized pharmaceutical carriers named nanoparticles (NPs) can support impressive management of disease not only in early detection and prognosis level but also in a therapeutic manner. The most prominent initiator of MS is the domination of cellular immunity to humoral immunity and increment of inflammatory cytokines. The administration of several platforms of NPs for MS management holds great promise so far. The efforts for MS management through in vitro and in vivo (experimental animal models) evaluations, pave a new way to a highly efficient therapeutic means and aiding its translation to the clinic in the near future.

Design and physico-mechanical evaluation of fast-dissolving valsartan polymeric drug delivery system by electrospinning method.

Objectives: Chronic hypertension is a pervasive morbidity and the leading risk factor for cardiovascular diseases. Valsartan, as an antihypertensive drug, has low solubility and bioavailability. The application of orodispersible films of valsartan is suggested to improve its bioavailability. With this dosage form, the drug dissolves rapidly in saliva and is absorbed readily without the need for water. Materials and Methods: For this purpose, valsartan with polyvinylpyrrolidone (PVPK90) polymer were exposed to the electrospinning technique to construct orodispersible nanofilms. The optimum obtained nanofiber, selected by Design-Expert software, was evaluated in terms of mechanical strength for evaluation of the flexibility and fragility of the nanofibers. The drug content, wettability, and disintegration tests, as well as the release assessment of the nanofibers, were performed followed by DSC, FTIR, and XRD assays. Results: The uniform nanofibers' diameter increased with the increase of the polymer concentration. The tensile test verified a stress reduction at the yield point as the polymer concentration increased. Then, the 492 nm nanofiber with above 90% drug encapsulation, containing 8% polymer and 18% valsartan made below 9 kV, was selected. The wetting time was less than 30 sec and over 90% of the drug was released in less than 2 min. The XRD and DSC studies also confirmed higher valsartan solubility due to the construction alternations in nanofibers. The FTIR examination indicated the chemical bonding between the drug and the polymer. Conclusion: The selected nanofibers of valsartan present the essential drug feature and acceptable drug release for further investigations.

An insight into the role of liposomal therapeutics in the reversion of multiple sclerosis.

INTRODUCTION: Multiple Sclerosis (MS), as an autoimmune disease, has complicated immunopathology, which makes its management relevant to various factors. Novel pharmaceutical vehicles, especially liposomes, can support efficacious handling of this disease both in early detection and prognosis and also in a therapeutic manner. The most well-known triggers of MS onset are the predominance of cellular to humoral immunity and enhancement of inflammatory cytokines level. The installation of liposomes as nanoparticles to control this disease holds great promise up to now. AREAS COVERED: Various types of liposomes with different properties and purposes have been formulated and targeted immune cells with their surface manipulations. They may be encapsulated with anti-inflammatory, MS-related therapeutics, or immunodominant myelin-specific peptides for attaining a higher therapeutic efficacy of the drugs or tolerance induction. Cationic liposomes are also highly applicable for gene delivery of the anti-inflammatory cytokines or silencing the inflammatory cytokines. Liposomes have also been used as biotools for comprehending MS pathomechanisms or as diagnostic agents. EXPERT OPINION: The efforts to manage MS through nanomedicine, especially liposomal therapeutics, pave a new avenue to a high-throughput medication of this autoimmune disease and their translation to the clinic in the future for overcoming the challenges that MS patients confront.