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1.
Clinical translation of advanced colonic drug delivery technologies.
Awad, A, Madla, CM, McCoubrey, LE, Ferraro, F, Gavins, FKH, Buanz, A, Gaisford, S, Orlu, M, Siepmann, F, Siepmann, J, et al
Advanced drug delivery reviews. 2022;:114076
Abstract
Targeted drug delivery to the colon offers a myriad of benefits, including treatment of local diseases, direct access to unique therapeutic targets and the potential for increasing systemic drug bioavailability and efficacy. Although a range of traditional colonic delivery technologies are available, these systems exhibit inconsistent drug release due to physiological variability between and within individuals, which may be further exacerbated by underlying disease states. In recent years, significant translational and commercial advances have been made with the introduction of new technologies that incorporate independent multi-stimuli release mechanisms (pH and/or microbiota-dependent release). Harnessing these advanced technologies offers new possibilities for drug delivery via the colon, including the delivery of biopharmaceuticals, vaccines, nutrients, and microbiome therapeutics for the treatment of both local and systemic diseases. This review details the latest advances in colonic drug delivery, with an emphasis on emerging therapeutic opportunities and clinical technology translation.
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2.
Withania somnifera in Neurological Disorders: Ethnopharmacological Evidence, Mechanism of Action and its Progress in Delivery Systems.
Syed, AA, Reza, MI, Singh, P, Thombre, GK, Gayen, JR
Current drug metabolism. 2021;(7):561-571
Abstract
BACKGROUND The underlying cause of major neurodegenerative disorders remains a healthcare mystery. The thoroughly investigated causes include oxidative stress, inflammation, environmental factor, mitochondrial dysfunction, and irregular neuronal protein aggregation. Withania somnifera has been used for more than 2500 years as a useful medicinal plant to improve disease defense, prevent aging, rejuvenate the body in a vulnerable situation, and generate a feeling of mental well-being. However, a persuasive paper emphasizing its neuroprotective nature is missing. OBJECTIVE In the current review, we have delineated the protective role of W. somnifera against various neurological disorders and its progress in delivery systems. METHODS The database used in the retrieval of data were PubMed, Scopus, Science direct, and SciFinder. The keywords used were W. somnifera, Ashwagandha, neuroprotective activities, etc. The principal source of the data retrieval includes research articles, review papers, and short communications from reputed publishers, including the New England Journal of Medicine, Elsevier, Nature, Springer, and Taylor & Francis. RESULTS After an extensive literature review, we found that W. somnifera mitigates various neurological disorders, including Parkinson's disease, Alzheimer's disease, Huntington disease, tardive dyskinesia, stroke, and anxiety. Furthermore, natural compounds in nano sizes range possess better neuroprotective activity. Consequently, polymeric nanomicelles, nanoparticles, and nanofibers of natural products are used in the treatment of neurodegenerative diseases. CONCLUSION The current review substantially deciphered the protective role of W. somnifera against various neurological disorders. However, future studies are further required better to understand the molecular mechanisms behind their neuroprotective nature.
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3.
Matrix metalloproteinase contribution in management of cancer proliferation, metastasis and drug targeting.
Abdel-Hamid, NM, Abass, SA
Molecular biology reports. 2021;(9):6525-6538
Abstract
Matrix metalloproteinases (MMPs) or matrixins, are members of a zinc-dependent endopeptidase family. They cause remodeling of the extracellular matrix (ECM) leading to numerous diseases. MMPs subfamilies possess: collagenases, gelatinases, stromelysins and membrane-type MMPs (MT-MMP). They consist of several domains; pro-peptide, catalytic, linker peptide and the hemopexin (Hpx) domains. MMPs are involved in initiation, proliferation and metastasis of cancer through the breakdown of ECM physical barriers. Overexpression of MMPs is associated with poor prognosis of cancer. This review will discuss both types of MMPs and current inhibitors, which target them in different aspects, including, biosynthesis, activation, secretion and catalytic activity. Several synthetic and natural inhibitors of MMPs (MMPIs) that can bind the catalytic domain of MMPs have been designed including; peptidomimetic, non-peptidomimetic, tetracycline derivatives, off-target MMPI, natural products, microRNAs and monoclonal antibodies.
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4.
Perspectives on Existing and Novel Alternative Intravaginal Probiotic Delivery Methods in the Context of Bacterial Vaginosis Infection.
Chandrashekhar, P, Minooei, F, Arreguin, W, Masigol, M, Steinbach-Rankins, JM
The AAPS journal. 2021;(3):66
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Abstract
Bacterial vaginosis (BV) is one of the most common vaginal infections that affects hundreds of millions of women of reproductive age, worldwide. Traditional treatment strategies, such as oral and topical antibiotics, have shown efficacy against BV, but frequent recurrence of infection and the development of antibiotic-resistant bacteria remain as significant challenges. Alternatively, recent progress in understanding immune, microbiological, and metabolic interactions in the vaginal microbiota has prompted the consideration of administering probiotic organisms to restore and maintain vaginal health within the context of BV prevention and treatment. Given this, the objective of this review is to discuss existing and potential alternative approaches to deliver, and to potentially sustain the delivery of probiotics, to prevent and/or treat BV infections. First, a brief overview is provided regarding the probiotic species and combinatorial probiotic strategies that have shown promise in the treatment of BV and in restoring female reproductive health. Additionally, the advantages and challenges associated with current oral and intravaginal probiotic delivery platforms are discussed. Lastly, we present emerging and promising alternative dosage forms, such as electrospun fibers and 3D bioprinted scaffolds, that may be adapted as new strategies to intravaginally deliver probiotic organisms. Graphical abstract.
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From Supramolecular Hydrogels to Multifunctional Carriers for Biologically Active Substances.
Skopinska-Wisniewska, J, De la Flor, S, Kozlowska, J
International journal of molecular sciences. 2021;(14)
Abstract
Supramolecular hydrogels are 3D, elastic, water-swelled materials that are held together by reversible, non-covalent interactions, such as hydrogen bonds, hydrophobic, ionic, host-guest interactions, and metal-ligand coordination. These interactions determine the hydrogels' unique properties: mechanical strength; stretchability; injectability; ability to self-heal; shear-thinning; and sensitivity to stimuli, e.g., pH, temperature, the presence of ions, and other chemical substances. For this reason, supramolecular hydrogels have attracted considerable attention as carriers for active substance delivery systems. In this paper, we focused on the various types of non-covalent interactions. The hydrogen bonds, hydrophobic, ionic, coordination, and host-guest interactions between hydrogel components have been described. We also provided an overview of the recent studies on supramolecular hydrogel applications, such as cancer therapy, anti-inflammatory gels, antimicrobial activity, controlled gene drug delivery, and tissue engineering.
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Tweak to Treat: Reprograming Bacteria for Cancer Treatment.
Sieow, BF, Wun, KS, Yong, WP, Hwang, IY, Chang, MW
Trends in cancer. 2021;(5):447-464
Abstract
Recent advancements in cancer biology, microbiology, and bioengineering have spurred the development of engineered live biotherapeutics for targeted cancer therapy. In particular, natural tumor-targeting and probiotic bacteria have been engineered for controlled and sustained delivery of anticancer agents into the tumor microenvironment (TME). Here, we review the latest advancements in the development of engineered bacteria for cancer therapy and additional engineering strategies to potentiate the delivery of therapeutic payloads. We also explore the use of combination therapies comprising both engineered bacteria and conventional anticancer therapies for addressing intratumor heterogeneity. Finally, we discuss prospects for the development and clinical translation of engineered bacteria for cancer prevention and treatment.
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The role of iron in doxorubicin-induced cardiotoxicity: recent advances and implication for drug delivery.
Qin, Y, Guo, T, Wang, Z, Zhao, Y
Journal of materials chemistry. B. 2021;(24):4793-4803
Abstract
As an anthracycline antibiotic, doxorubicin (DOX) is one of the most potent and widely used chemotherapeutic agents for treating various types of tumors. Unfortunately, the clinical application of this drug results in severe side effects, particularly dose-dependent cardiotoxicity. There are multiple mechanisms involved with the cardiotoxicity caused by DOX, among which intracellular iron homeostasis plays an essential role based on a recent discovery. In this mini-review, we summarize the clinical features and symptoms of DOX-dependent cardiotoxicity, discuss the correlation between iron and cardiotoxicity, and highlight the involvement of iron-dependent ferroptotic cell death therein. Recent advances in this topic will aid the development of novel DOX delivery systems with reduced adverse effects, and expand the clinical application of anthracycline.
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Circulating miRNAs in diabetic retinopathy patients: Prognostic markers or pharmacological targets?
Trotta, MC, Gesualdo, C, Platania, CBM, De Robertis, D, Giordano, M, Simonelli, F, D'Amico, M, Drago, F, Bucolo, C, Rossi, S
Biochemical pharmacology. 2021;:114473
Abstract
In this study we analyzed the expression of circulating miRNAs, in the serum of diabetic retinopathy (DR) patients. Five miRNAs (hsa-miR-195-5p, hsa-miR-20a-5p, hsa-miR-20b-5p, hsa-miR-27b-3p and hsa-miR-451a) were validated as biomarkers for stratification of DR stages, from the early non-proliferative (NPDR) to the late proliferative (PDR) phase. Furthermore, circulating levels of these miRNAs correlated with retinal hyper-reflective spots (HRS), assessed by optical coherence tomography (OCT). The number of HRS increased with worsening of DR stages. On the contrary, no significant vascular density differences between NPDR and PDR patients were detected by angio-OCT (OCTA). A post-hoc bioinformatics analysis associated these five miRNAs to target genes belonging to the "Tumor Necrosis Factor alfa signaling" pathway, and several molecules were predicted to modify miRNAs expression. In conclusion, correlation between specific circulating miRNAs and intraretinal hyper-reflective spots was demonstrated, confirming that these miRNAs were validated as prognostic biomarkers, and also as potential pharmacological targets, warranting further clinical evaluation to explore novel therapeutics for diabetic retinopathy.
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Pullulan biosynthesis and its regulation in Aureobasidium spp.
Wei, X, Liu, GL, Jia, SL, Chi, Z, Hu, Z, Chi, ZM
Carbohydrate polymers. 2021;:117076
Abstract
It has been well known that different strains of Aureobasidium spp. can yield a large amount of pullulan. Although pullulan has wide applications in various sectors of biotechnology, its biosynthesis and regulation were not resolved. Lately, the molecular mechanisms of pullulan biosynthesis and regulation have been elucidated and their genes and encoding proteins have been identified using the genome-wide mutant analysis. It is found that a multidomain AmAgs2 is the key enzyme for pullulan biosynthesis and the alternative primers are required for its biosynthesis. Pullulan biosynthesis is regulated by glucose repression and signaling pathways. Elucidation of such a biosynthetic pathway and regulation is of significance in biotechnology. Therefore, the present review article mainly summaries the recent research proceedings in this field, hoping to promote further endeavors on enhanced pullulan production and improved chemical properties of pullulan via molecular modifications of the producers by using synthetic biology approaches.
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Recent advances in dextran-based drug delivery systems: From fabrication strategies to applications.
Hu, Q, Lu, Y, Luo, Y
Carbohydrate polymers. 2021;:117999
Abstract
As a natural polysaccharide, dextran and its derivatives have gained great attention in the development of delivery systems for pharmaceutical and medical applications. In recent years, numerous dextran-based delivery systems with tailor properties and geometries have been developed, including self-assembled micelles and nanoparticles, nanoemulsions, magnetic nanoparticles, microparticles, and hydrogels. The first part of this review discusses the physicochemical properties of dextran and its various derivatives via chemical modifications, as pertinent to the preparation of delivery systems. Then, the state-of-the-art fabrication strategies of dextran-based delivery systems and their colloidal properties, i.e. particle diameter, surface charge, morphology, as well as release profiles, are highlighted. Lastly, applications of dextran-based drug delivery systems in biomedicine are explicitly summarized with detailed elaborations on their biological efficacy and mechanism of action, including cancer treatment, magnetic resonance imaging, insulin oral delivery, spinal cord injury therapy, and bacterial skin infection treatment.