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1.
Cell Death Dis ; 15(1): 17, 2024 01 08.
Article in English | MEDLINE | ID: mdl-38191571

ABSTRACT

Cancer is one of the most common diseases and causes of death worldwide. Since common treatment approaches do not yield acceptable results in many patients, developing innovative strategies for effective treatment is necessary. Immunotherapy is one of the promising approaches that has been highly regarded for preventing tumor recurrence and new metastases. Meanwhile, inhibiting immune checkpoints is one of the most attractive methods of cancer immunotherapy. Cytotoxic T lymphocyte-associated protein-4 (CTLA-4) is an essential immune molecule that plays a vital role in cell cycle modulation, regulation of T cell proliferation, and cytokine production. This molecule is classically expressed by stimulated T cells. Inhibition of overexpression of immune checkpoints such as CTLA-4 receptors has been confirmed as an effective strategy. In cancer immunotherapy, immune checkpoint-blocking drugs can be enhanced with nanobodies that target immune checkpoint molecules. Nanobodies are derived from the variable domain of heavy antibody chains. These small protein fragments have evolved entirely without a light chain and can be used as a powerful tool in imaging and treating diseases with their unique structure. They have a low molecular weight, which makes them smaller than conventional antibodies while still being able to bind to specific antigens. In addition to low molecular weight, specific binding to targets, resistance to temperature, pH, and enzymes, high ability to penetrate tumor tissues, and low toxicity make nanobodies an ideal approach to overcome the disadvantages of monoclonal antibody-based immunotherapy. In this article, while reviewing the cellular and molecular functions of CTLA-4, the structure and mechanisms of nanobodies' activity, and their delivery methods, we will explain the advantages and challenges of using nanobodies, emphasizing immunotherapy treatments based on anti-CTLA-4 nanobodies.


Subject(s)
Neoplasms , Single-Domain Antibodies , Humans , CTLA-4 Antigen , Single-Domain Antibodies/therapeutic use , Immunotherapy , Immune Checkpoint Proteins , Antibodies, Monoclonal , Neoplasms/therapy
2.
RSC Adv ; 13(49): 34587-34597, 2023 Nov 22.
Article in English | MEDLINE | ID: mdl-38024994

ABSTRACT

The anticancer properties of curcumin have been broadly examined in several shapes, such as nanoparticles and nanocomposite structures. Despite its benefits, curcumin also has some disadvantages, including rapid metabolism, poor absorption, and rapid systemic excretion. Therefore, numerous strategies have been used to increase curcumin's bioavailability. One of these approaches is the use of porous particles like aerogels as drug carriers. Aerogels are special due to their peculiar physical structure. They have a high specific surface area, a significant amount of porosity, and a solid composition, which make them a good choice for drug delivery systems. In the present study, a pH-sensitive aerogel was constructed and evaluated for targeted drug delivery of curcumin to colon cancer. To control the release of curcumin, trehalose was used as a coating agent, and PLP (poly(l-lysine isophthalamide)) was used as a targeted drug delivery agent. PLP is a pseudo-peptidic polymer that increases the cell permeability. In order to investigate and compare the synthesized aerogel before and after loading curcumin and coating with trehalose, physicochemical characterization analyses were performed. Finally, the efficacy of the final formulation was evaluated on HT29 colon cells using the cell bioavailability test. The results indicated the successful synthesis of the aerogel with porous structure with solitary cavities. The trehalose coating performed well, preventing drug release at lower pH but allowing the drug to be released at its intended site. The designed curcumin-loaded porous particles functionalized with PLP showed significant efficacy due to increasing penetration of curcumin into cells, and has potential for use as a new drug carrier with dual effectivity in cancer therapy.

3.
Eur J Med Chem ; 260: 115765, 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-37659194

ABSTRACT

Targeted Protein Modification (TPM) is an umbrella term encompassing numerous tools and approaches that use bifunctional agents to induce a desired modification over the POI. The most well-known TPM mechanism is PROTAC-directed protein ubiquitination. PROTAC-based targeted degradation offers several advantages over conventional small-molecule inhibitors, has shifted the drug discovery paradigm, and is acquiring increasing interest as over ten PROTACs have entered clinical trials in the past few years. Targeting the protein of interest for proteasomal degradation by PROTACS was the pioneer of various toolboxes for selective protein degradation. Nowadays, the ever-increasing number of tools and strategies for modulating and modifying the POI has expanded far beyond protein degradation, which phosphorylation and de-phosphorylation of the protein of interest, targeted acetylation, and selective modification of protein O-GlcNAcylation are among them. These novel strategies have opened new avenues for achieving more precise outcomes while remaining feasible and minimizing side effects. This field, however, is still in its infancy and has a long way to precede widespread use and translation into clinical practice. Herein, we investigate the pros and cons of these novel strategies by exploring the latest advancements in this field. Ultimately, we briefly discuss the emerging potential applications of these innovations in cancer therapy, neurodegeneration, viral infections, and autoimmune and inflammatory diseases.


Subject(s)
Drug Discovery , Protein Processing, Post-Translational , Proteolysis , Phosphorylation , Ubiquitination , Proteolysis Targeting Chimera
4.
Front Bioeng Biotechnol ; 11: 1115254, 2023.
Article in English | MEDLINE | ID: mdl-37600314

ABSTRACT

Perfluorocarbon (PFC) are biocompatible compounds, chemically and biologically inert, and lacks toxicity as oxygen carriers. PFCs nanoemulsions and nanoparticles (NPs) are highly used in diagnostic imaging and enable novel imaging technology in clinical imaging modalities to notice and image pathological and physiological alterations. Therapeutics with PFCs such as the innovative approach to preventing thrombus formation, PFC nanodroplets utilized in ultrasonic medication delivery in arthritis, or PFC-based NPs such as Perfluortributylamine (PFTBA), Pentafluorophenyl (PFP), Perfluorohexan (PFH), Perfluorooctyl bromide (PFOB), and others, recently become renowned for oxygenating tumors and enhancing the effects of anticancer treatments as oxygen carriers for tumor hypoxia. In this review, we will discuss the recent advancements that have been made in PFC's applications in theranostic (therapeutics and diagnostics) as well as assess the benefits and drawbacks of these applications.

5.
Biomed Pharmacother ; 166: 115408, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37651798

ABSTRACT

Parkinson's disease (PD) is a progressive disorder that belongs to a class of neurodegenerative disorders (NDs) called Synucleinopathies. It has characterized by the misfolding and aggregation of a-synuclein. Our understanding of PD continues to evolve, and so does our approach to treatment. including therapies aimed at delaying pathology, quitting neuronal loss, and shortening the course of the disease by selectively targeting essential proteins suspected to play a role in PD pathogenesis. One emerging approach that is generating significant interest is Targeted Protein Degradation (TPD). TPD is an innovative method that allows us to specifically break down certain proteins using specially designed molecules or peptides, like PROteolysis-TArgeting-Chimera (PROTACs). This approach holds great promise, particularly in the context of NDs. In this review, we will briefly explain PD and its pathogenesis, followed by discussing protein degradation systems and TPD strategy in PD by reviewing synthesized small molecules and peptides. Finally, future perspectives and challenges in the field are discussed.


Subject(s)
Parkinson Disease , Humans , Proteolysis , Parkinson Disease/drug therapy , Proteolysis Targeting Chimera
6.
Materials (Basel) ; 16(7)2023 Mar 31.
Article in English | MEDLINE | ID: mdl-37049093

ABSTRACT

Bone tissue engineering integrates biomaterials, cells, and bioactive agents to propose sophisticated treatment options over conventional choices. Scaffolds have central roles in this scenario, and precisely designed and fabricated structures with the highest similarity to bone tissue have shown promising outcomes. On the other hand, using nanotechnology and nanomaterials as the enabling options confers fascinating properties to the scaffolds, such as precisely tailoring the physicochemical features and better interactions with cells and surrounding tissues. Among different nanomaterials, polymeric nanofibers and carbon nanofibers have attracted significant attention due to their similarity to bone extracellular matrix (ECM) and high surface-to-volume ratio. Moreover, bone ECM is a biocomposite of collagen fibers and hydroxyapatite crystals; accordingly, researchers have tried to mimic this biocomposite using the mineralization of various polymeric and carbon nanofibers and have shown that the mineralized nanofibers are promising structures to augment the bone healing process in the tissue engineering scenario. In this paper, we reviewed the bone structure, bone defects/fracture healing process, and various structures/cells/growth factors applicable to bone tissue engineering applications. Then, we highlighted the mineralized polymeric and carbon nanofibers and their fabrication methods.

7.
Int J Biol Macromol ; 235: 123766, 2023 Apr 30.
Article in English | MEDLINE | ID: mdl-36841390

ABSTRACT

The main purpose of this study is to synthesize and characterize Persian gum-based hydrogel composited with gentamicin (Gen)-loaded natural zeolite (Clinoptilolite) and to evaluate its biological properties. Clinoptilolite (CLN) was decorated with Gen, and the conjugation was confirmed using computational and experimental assessments. The Monte Carlo adsorption locator module was used to reveal the physicochemical nature of the adsorption processes of Gen on CLN and ALG and gum on Gen@ CLN in Materials Studio 2017 software. Based on the high negative results, the adsorption process was found to be endothermic in all studied cases, and the interaction energies were in the range of physisorption for Gen on CLN and ALG and gum on Gen@CLN. Dynamic light scattering (DLS) and zeta potential analysis showed that the size of pristine CLN was around 2959 nm and the conjugation decreased the size significantly to approximately 932 nm. The hydrogel characterizations showed that the Gen-decorated CLNs are homogenously dispersed into the hydrogel matrix, and the resultant hydrogels have a porous structure with interconnected pores. The release kinetics evaluation showed that around 80 % of Gen was released from the nanocomposite drug during the first 10 h. In vitro studies revealed hemocompatibility and cytocompatibility of the nanocomposite. Microbial assessments indicated dose-dependent antibacterial activity of the hydrogel against gram (+) and gram (-) bacteria. The results showed that the fabricated hydrogel nanocomposite exhibits favorable physicochemical and biological properties.


Subject(s)
Gentamicins , Zeolites , Gentamicins/pharmacology , Gentamicins/chemistry , Hydrogels/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry
8.
ACS Omega ; 8(1): 771-781, 2023 Jan 10.
Article in English | MEDLINE | ID: mdl-36643496

ABSTRACT

Ischemic stroke accompanies oxidative stress and cell death in the cerebral tissue. The microRNA miR-34a plays a pivotal role in this molecular pathology. This study presents the rational repositioning of aminoglycosidic antibiotics as miR-34a antagonists in order to assess their efficiency in protecting the PC12 stroke model cells from oxidative stress occurring under cerebral ischemic conditions. A library of 29 amino-sugar compounds were screened against anticipated structural models of miR-34a through molecular docking. MiR-ligand interactions were mechanistically studied by molecular dynamics simulations and free-energy calculations. Cultured PC12 cells were treated by H2O2 alone or in combination with gentamycin and neomycin as selected drugs. Cell viability and apoptosis were detected by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) and annexin V-FITC/propidium iodate (PI) double staining assays, respectively. The expression levels of key factors involved in cell proliferation, oxidative stress, and apoptosis in treated PC12 cells were measured through a quantitative real-time polymerase chain reaction and flow cytometric annexin V-FITC/PI double staining assays. A stable and energetically favorable binding was observed for miR-34a with gentamycin and neomycin. Gentamycin pretreatments followed by H2O2 oxidative injury led to increased cell viability and protected PC12 cells against H2O2-induced apoptotic events. This study will help in further understanding how the suppression of miR-34a in neural tissue affects the cell viability upon stroke.

9.
Biology (Basel) ; 11(10)2022 Oct 08.
Article in English | MEDLINE | ID: mdl-36290377

ABSTRACT

The main aim of the current study is to fabricate an osteocompatible, bioactive, porous, and degradable bone tissue engineering scaffold. For this purpose, bioactive glasses (BGs) were chosen due to their similarity to bone's natural mineral composition, and the effect of replacing Ca ions with Sr on their properties were considered. First, strontium-containing BGs (Sr-BGs) were synthesized using the electrospinning technique and assembled by the sol-gel method, then they were incorporated into the alginate (Alg) matrix. Photographs of the scanning electron microscope (SEM) showed that the BG nanofibers have a diameter of 220 ± 36 nm, which was smaller than the precursor nanofibers (275 ± 66 nm). The scaffolds possess a porous internal microstructure (230-330 nm pore size) with interconnected pores. We demonstrated that the scaffolds could be degraded in the acetate sodium buffer and phosphate-buffered saline. The osteoactivity of the scaffolds was confirmed via visual inspection of the SEM illustrations after seven days of immersing them in the SBF solution. In vitro assessments disclosed that the produced Alg-based composites including Sr-BGs (Alg/Sr-BGs) are blood-compatible and biocompatible. Accumulating evidence shows that Alg/Sr-BG (5%, 10%, and 15%) hydrogels could be a promising scaffold for bone regeneration.

10.
Tissue Eng Part B Rev ; 28(5): 1053-1066, 2022 10.
Article in English | MEDLINE | ID: mdl-34696626

ABSTRACT

Type 1 diabetes (T1D) is caused by low insulin production and chronic hyperglycemia due to destruction of pancreatic ß-cells. Cell transplantation is an attractive alternative approach compared to insulin injection. However, cell therapy has been limited by major challenges, including life-long requirement for immunosuppressive drugs to prevent host immune responses. Encapsulation of the transplanted cells can solve the problem of immune rejection, by providing a physical barrier between the transplanted cells and the recipient's immune cells. Despite current disputes in cell encapsulation approaches, thanks to recent advances in the fields of biomaterials and transplantation immunology, extensive effort has been dedicated to immunoengineering strategies, in combination with encapsulation technologies, to overcome the problem of host's immune responses. This review summarizes the most commonly used encapsulation and immunoengineering strategies combined with cell therapy, which have been applied as a novel approach to improve cell replacement therapies for management of T1D. Recent advances in the fields of biomaterial design, nanotechnology, as well as deeper knowledge about immune modulation had significantly improved cell encapsulation strategies. However, further progress requires combined application of novel immunoengineering approaches and islet/ß-cell transplantation. Impact statement Cell encapsulation shows promising potential in preventing host's immune responses and rejection of islets or ß-cells by providing a selectively permeable barrier between the host and the transplanted cells. Innovative materials, conformal nanocoatings, and immunomodulation have provided promising approaches in the field of encapsulation technology. Novel nanocarriers have been synthesized to release and deliver immunosuppressive agents to islets/ß-cells within the capsules in a controlled manner. The immunoengineering approach (immunosuppressive and immunomodulatory agents) could overcome the challenges of cell replacement therapy in type 1 diabetes.


Subject(s)
Diabetes Mellitus, Type 1 , Insulins , Islets of Langerhans Transplantation , Islets of Langerhans , Humans , Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 1/metabolism , Biocompatible Materials , Capsules/metabolism , Islets of Langerhans/metabolism , Immunosuppressive Agents/metabolism , Insulins/metabolism
11.
ACS Chem Neurosci ; 12(24): 4475-4490, 2021 12 15.
Article in English | MEDLINE | ID: mdl-34841846

ABSTRACT

The blood-brain barrier (BBB) is considered as the most challenging barrier in brain drug delivery. Indeed, there is a definite link between the BBB integrity defects and central nervous systems (CNS) disorders, such as neurodegenerative diseases and brain cancers, increasing concerns in the contemporary era because of the inability of most therapeutic approaches. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have already been identified as having several advantages in facilitating the transportation of hydrophilic and hydrophobic agents across the BBB. This review first explains BBB functions and its challenges in brain drug delivery, followed by a brief description of nanoparticle-based drug delivery for brain diseases. A detailed presentation of recent progressions in optimizing SLNs and NLCs for controlled release drug delivery, gene therapy, targeted drug delivery, and diagnosis of neurodegenerative diseases and brain cancers is approached. Finally, the problems, challenges, and future perspectives in optimizing these carriers for potential clinical application were described briefly.


Subject(s)
Blood-Brain Barrier , Nanoparticles , Drug Carriers , Drug Delivery Systems , Lipids , Liposomes
12.
Nanomedicine (Lond) ; 16(13): 1133-1151, 2021 06.
Article in English | MEDLINE | ID: mdl-33973797

ABSTRACT

The wide prevalence of oxidative stress-induced diseases has led to a growing demand for antioxidant therapeutics worldwide. Nanozyme antioxidants are drawing enormous attention as practical alternatives for conventional antioxidants. The considerable body of research over the last decade and the promising results achieved signify the potential of nanozyme antioxidants to secure a place in the expanding market of antioxidant therapeutics. Nonetheless, there is no report on clinical trials for their further evaluation. Through analyzing in-depth selected papers which have conducted in vivo studies on nanozyme antioxidants, this review aims to pinpoint and discuss possible reasons impeding development of research toward clinical studies and to offer some practical solutions for future studies to bridge the gap between preclinical and clinical stages.


Lay abstract "We did not experience these kinds of strange illnesses in the past." Everybody might have heard such a familiar sentence from their grandparents and asked themselves, why? The current paper aims to provide readers with one of the answers: "Oxidative stress", which happens when the body fails to neutralize damage caused by unstable molecules called free radicals. In this paper, the authors present the seriousness of oxidative stress-induced clinical conditions. They discuss one of the promising treatments, nanozyme antioxidants, these are mostly based on nano-sized materials with enzyme-like function, in other words, they can speed up chemical reactions. Despite significant results, nanozyme antioxidants have not been investigated in clinical studies. This paper intends to search for the main reasons for this and suggest possible solutions.


Subject(s)
Antioxidants , Oxidative Stress
13.
BMC Complement Med Ther ; 21(1): 111, 2021 Apr 07.
Article in English | MEDLINE | ID: mdl-33827547

ABSTRACT

BACKGROUND: Interactive dressings are innovatively designed to interact with the wound surface and alter the wound environment to promote wound healing. In the current study, we integrated the physicochemical properties of Poly (caprolactone)/ Poly (vinyl alcohol)/Collagen (PCL/PVA/Col) nanofibers with the biological activities of Momordica charantia pulp extract to develop an efficient wound dressing. The electrospinning method was applied to fabricate the nanofibers, and the prepared wound dressings were thoroughly characterized. RESULTS: SEM imaging showed that the nanofibers were uniform, straight, without any beds with a diameter in the range of 260 to 480 nm. Increasing the concentration of the extract increased the diameter of the nanofibers and also the wettability characteristics while reduced the ultimate tensile strength from 4.37 ± 0.90 MPa for PCL/PVA/Col to 1.62 ± 0.50 MPa for PCL/PVA/Col/Ex 10% (p < 0.05). The in vivo studies showed that the application of the wound dressings significantly enhanced the healing process and the highest wound closure, 94.01 ± 8.12%, was obtained by PCL/PVA/Col/Ex 10% nanofibers (p < 0.05). CONCLUSION: The incorporation of the extract had no significant effects on nanofibers' porosity, water vapor permeability, and swelling characteristics. The in vitro evaluations showed that the fabricated nanofibers were hemocompatible, cytocompatible, and prevent bacterial penetration through the dressing. These findings implied that the PCL/PVA/Col/Ex nanofibers can be applied as the wound dressing materials.


Subject(s)
Bandages , Momordica charantia , Nanofibers/chemistry , Plant Extracts/therapeutic use , Animals , Cell Culture Techniques , Male , Polyvinyl Alcohol/chemistry , Rats , Wound Healing/drug effects
14.
J Biomol Struct Dyn ; 39(9): 3256-3262, 2021 Jun.
Article in English | MEDLINE | ID: mdl-32345145

ABSTRACT

In the present work, we studied the structure-activity relationship and kinetics of thermal inactivation of α-glucosidase A (AglA) in a 50 mM potassium phosphate buffer at pH 6.8 using p-nitrophenyl α-d-glucopyranoside (pNPG) as the synthetic substrate following absorbance at 410 nm by UV-Vis spectrophotometer. The interface structure and residual activity plot were analyzed via biochemical measurements by means of conformational lock theory, as well. The thermal inactivation curves were plotted in temperature interval from 30 to 50 °C. Based on experimental and structural data we suggested intermediates during inactivation before the loss of enzyme activity. Arrhenius plot for thermal inactivation rate constant showed biphasic appearance related to before and after 45°C temperature. The contact areas between two subunits were ruptured and unlocked stepwise during dimer dissociation. Cleavage of these areas induced the dissociation of the subunits along with destruction of the active centers and subsequently the loss of activity. It seems that the contact areas interact with active centers by conformational changes involving secondary structural elements.


Subject(s)
alpha-Glucosidases , Enzyme Stability , Hydrogen-Ion Concentration , Kinetics , Protein Conformation , Temperature , alpha-Glucosidases/metabolism
15.
Mar Drugs ; 20(1)2021 Dec 23.
Article in English | MEDLINE | ID: mdl-35049874

ABSTRACT

In the current paper, we fabricated, characterized, and applied nanocomposite hydrogel based on alginate (Alg) and nano-hydroxyapatite (nHA) loaded with phenolic purified extracts from the aerial part of Linum usitatissimum (LOH) as the bone tissue engineering scaffold. nHA was synthesized based on the wet chemical technique/precipitation reaction and incorporated into Alg hydrogel as the filler via physical cross-linking. The characterizations (SEM, DLS, and Zeta potential) revealed that the synthesized nHA possess a plate-like shape with nanometric dimensions. The fabricated nanocomposite has a porous architecture with interconnected pores. The average pore size was in the range of 100-200 µm and the porosity range of 80-90%. The LOH release measurement showed that about 90% of the loaded drug was released within 12 h followed by a sustained release over 48 h. The in vitro assessments showed that the nanocomposite possesses significant antioxidant activity promoting bone regeneration. The hemolysis induction measurement showed that the nanocomposites were hemocompatible with negligible hemolysis induction. The cell viability/proliferation confirmed the biocompatibility of the nanocomposites, which induced proliferative effects in a dose-dependent manner. This study revealed the fabricated nanocomposites are bioactive and osteoactive applicable for bone tissue engineering applications.


Subject(s)
Alginates/pharmacology , Bone and Bones/drug effects , Durapatite/pharmacology , Flax , Plant Extracts/pharmacology , Tissue Scaffolds , Alginates/chemistry , Aquatic Organisms , Bone Regeneration , Cell Line/drug effects , Durapatite/chemistry , Humans , Nanocomposites , Plant Extracts/chemistry
16.
Sci Rep ; 10(1): 14569, 2020 09 03.
Article in English | MEDLINE | ID: mdl-32884004

ABSTRACT

This scenario was designed to investigate the protein corona pattern on the pillar-layer surface of a Cu-based metal-organic framework (MOF) in human plasma. The [Cu(L)(L/)].1.3DMA (MOF-1) {L = 4, 4/-bipyridine and L/ = 5-aminoisophthalic acid}, was synthesized through the sonochemical irradiation approach as well as characterized by various techniques like scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray powder diffraction and single-crystal X-ray diffraction. The space group was determined to be an orthorhombic space group (Pbam) by single-crystal X-ray diffraction. Single-crystal X-ray analyses on MOF-1 showed that Cu+2 ion was 6-coordinated. Besides, to study and clarify interactions between MOFs and biological milieu, human whole blood plasma was selected as a model. Fluorescence spectroscopy and SDS-PAGE techniques were employed to explore quantitative and qualitative in situ characterization of protein corona as well. Furthermore, cell viability in a cancerous cell lines was evaluated by MTT assay in the presence and absence of the corona. The results from SDS-PAGE illustrated that the most adsorbed quantity among plasma proteins belongs to fibrinogen (α, ß and γ chains), and this protein showed the maximum frequency on the MOF-1s surface, so the possible interactions of MOF-1s with fibrinogen also studied using fluorescence spectroscopy and corresponding data were plotted. According to the obtained data from MTT assay, these structures have concentration-dependent toxicity. In brief, based on the obtained data in the current study, the designed MOF can be introduced as a new desirable carrier for drug/gen delivery after further prerequisite assessments.


Subject(s)
Breast Neoplasms/pathology , Cell Proliferation , Metal-Organic Frameworks/pharmacology , Protein Corona/chemistry , Serum Albumin, Human/pharmacology , Serum Globulins/pharmacology , Breast Neoplasms/drug therapy , Drug Delivery Systems , Female , Humans , MCF-7 Cells , Metal-Organic Frameworks/chemistry
17.
Article in English | MEDLINE | ID: mdl-32478050

ABSTRACT

Metabolic syndrome includes a series of metabolic abnormalities that leads to diabetes mellitus and cardiovascular diseases. Plant extracts, due to their unique advantages like anti-inflammatory, antioxidant, and insulin sensitizing properties, are interesting therapeutic options to manage MetS; however, the poor solubility and low bioavailability of lipophilic bioactive components in the herbal extracts are two critical challenges. Nano-scale delivery systems are suitable to improve delivery of herbal extracts. This review, for the first time, focuses on nanoformulations of herbal extracts in MetS and related complications. Included studies showed that several forms of nano drug delivery systems such as nanoemulsions, solid lipid nanoparticles, nanobiocomposites, and green-synthesized silver, gold, and zinc oxide nanoparticles have been developed using herbal extracts. It was shown that the method of preparation and related parameters such as temperature and type of polymer are important factors affecting physicochemical stability and therapeutic activity of the final product. Many of these formulations could successfully decrease the lipid profile, inflammation, oxidative damage, and insulin resistance in in vitro and in vivo models of MetS-related complications. Further studies are still needed to confirm the safety and efficacy of these novel herbal formulations for clinical application.

18.
Curr Drug Deliv ; 17(5): 375-386, 2020.
Article in English | MEDLINE | ID: mdl-32294035

ABSTRACT

The passage of therapeutic molecules across the Blood-Brain Barrier (BBB) is a profound challenge for the management of the Central Nervous System (CNS)-related diseases. The ineffectual nature of traditional treatments for CNS disorders led to the abundant endeavor of researchers for the design the effective approaches in order to bypass BBB during recent decades. Cell-Penetrating Peptides (CPPs) were found to be one of the promising strategies to manage CNS disorders. CPPs are short peptide sequences with translocation capacity across the biomembrane. With special regard to their two key advantages like superior permeability as well as low cytotoxicity, these peptide sequences represent an appropriate solution to promote therapeutic/theranostic delivery into the CNS. This scenario highlights CPPs with specific emphasis on their applicability as a novel theranostic delivery system into the brain.


Subject(s)
Blood-Brain Barrier/metabolism , Cell-Penetrating Peptides/administration & dosage , Central Nervous System Diseases/diagnosis , Central Nervous System Diseases/drug therapy , Animals , Drug Stability , Humans , Precision Medicine
19.
Int J Nanomedicine ; 15: 363-386, 2020.
Article in English | MEDLINE | ID: mdl-32021185

ABSTRACT

The advent of porous materials, in particular zeolitic nanoparticles, has opened up unprecedented putative research avenues in nanomedicine. Zeolites with intracrystal mesopores are low framework density aluminosilicates possessing a regular porous structure along with intricate channels. Their unique physiochemical as well as physiological parameters necessitate a comprehensive overview on their classifications, fabrication platforms, cellular/macromolecular interactions, and eventually their prospective biomedical applications through illustrating the challenges and opportunities in different integrative medical and pharmaceutical fields. More particularly, an update on recent advances in zeolite-accommodated drug delivery and the prevalent challenges regarding these molecular sieves is to be presented. In conclusion, strategies to accelerate the translation of these porous materials from bench to bedside along with common overlooked physiological and pharmacological factors of zeolite nanoparticles are discussed and debated. Furthermore, for zeolite nanoparticles, it is a matter of crucial importance, in terms of biosafety and nanotoxicology, to appreciate the zeolite-bio interface once the zeolite nanoparticles are exposed to the bio-macromolecules in biological media. We specifically shed light on interactions of zeolite nanoparticles with fibrinogen and amyloid beta which had been comprehensively investigated in our recent reports. Given the significance of zeolite nanoparticles' interactions with serum or interstitial proteins conferring them new biological identity, the preliminary approaches for deeper understanding of administration, distribution, metabolism and excretion of zeolite nanoparticles are elucidated.


Subject(s)
Nanomedicine/methods , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Zeolites/chemistry , Amyloid beta-Peptides/metabolism , Animals , Contrast Media/chemistry , Drug Delivery Systems/methods , Fibrinogen/metabolism , Gastrointestinal Diseases/therapy , Humans , Hydrogels/chemistry , Magnetic Resonance Imaging/methods , Nanoparticles/toxicity , Osteogenesis , Porosity , Renal Dialysis
20.
Nanomedicine ; 24: 102149, 2020 02.
Article in English | MEDLINE | ID: mdl-31927133

ABSTRACT

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease which leads to progressive dysfunction of cognition, memory and learning in elderly people. Common therapeutic agents are not only inadequate to suppress the progression of AD pathogenesis but also produce deleterious side effects; hence, development of alternative therapies is required to specifically suppress complications of AD. The current review provides a commentary on conventional as well as novel therapeutic approaches with an emphasis on stem cell and nano-based therapies for improvement and management of AD pathogenesis. According to our overview of the current literature, AD is a multi-factorial disorder with various pathogenic trajectories; hence, a multifunctional strategy to create effective neuroprotective agents is required to treat this disorder.


Subject(s)
Alzheimer Disease/pathology , Cell- and Tissue-Based Therapy/methods , Neurodegenerative Diseases/pathology , Alzheimer Disease/therapy , Animals , Humans , Neurodegenerative Diseases/therapy
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