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1.
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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2.
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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3.
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.
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4.
Nanotechnological approach to delivering nutraceuticals as promising drug candidates for the treatment of atherosclerosis.
Pillai, SC, Borah, A, Jacob, EM, Kumar, DS
Drug delivery. 2021;(1):550-568
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Abstract
Atherosclerosis is Caesar's sword, which poses a huge risk to the present generation. Understanding the atherosclerotic disease cycle would allow ensuring improved diagnosis, better care, and treatment. Unfortunately, a highly effective and safe way of treating atherosclerosis in the medical community remains a continuous challenge. Conventional treatments have shown considerable success, but have some adverse effects on the human body. Natural derived medications or nutraceuticals have gained immense popularity in the treatment of atherosclerosis due to their decreased side effects and toxicity-related issues. In hindsight, the contribution of nutraceuticals in imparting enhanced clinical efficacy against atherosclerosis warrants more experimental evidence. On the other hand, nanotechnology and drug delivery systems (DDS) have revolutionized the way therapeutics are performed and researchers have been constantly exploring the positive effects that DDS brings to the field of therapeutic techniques. It could be as exciting as ever to apply nano-mediated delivery of nutraceuticals as an additional strategy to target the atherosclerotic sites boasting high therapeutic efficiency of the nutraceuticals and fewer side effects.
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Embracing Defects and Disorder in Magnetic Nanoparticles.
Lak, A, Disch, S, Bender, P
Advanced science (Weinheim, Baden-Wurttemberg, Germany). 2021;(7):2002682
Abstract
Iron oxide nanoparticles have tremendous scientific and technological potential in a broad range of technologies, from energy applications to biomedicine. To improve their performance, single-crystalline and defect-free nanoparticles have thus far been aspired. However, in several recent studies, defect-rich nanoparticles outperform their defect-free counterparts in magnetic hyperthermia and magnetic particle imaging (MPI). Here, an overview on the state-of-the-art of design and characterization of defects and resulting spin disorder in magnetic nanoparticles is presented with a focus on iron oxide nanoparticles. The beneficial impact of defects and disorder on intracellular magnetic hyperthermia performance of magnetic nanoparticles for drug delivery and cancer therapy is emphasized. Defect-engineering in iron oxide nanoparticles emerges to become an alternative approach to tailor their magnetic properties for biomedicine, as it is already common practice in established systems such as semiconductors and emerging fields including perovskite solar cells. Finally, perspectives and thoughts are given on how to deliberately induce defects in iron oxide nanoparticles and their potential implications for magnetic tracers to monitor cell therapy and immunotherapy by MPI.
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The use of nanotechnology to combat liver cancer: Progress and perspectives.
Mintz, KJ, Leblanc, RM
Biochimica et biophysica acta. Reviews on cancer. 2021;(2):188621
Abstract
Liver cancer is one of the most common cancers worldwide and is also one of the most difficult cancers to treat, resulting in almost one million deaths per year, and the danger of this cancer is compounded when the tumor is nonresectable. Hepatocellular carcinoma (HCC) is the most common type of liver cancer and has the third highest mortality rate worldwide. Considering the morbid statistics surrounding this cancer it is a popular research topic to target for better therapy practices. This review summarizes the role of nanotechnology in these endeavors. Nanoparticles (NPs) are a very broad class of material and many different kinds have been used to potentially combat liver cancer. Gold, silver, platinum, metal oxide, calcium, and selenium NPs as well as less common materials are all inorganic NPs that have been used as a therapeutic, carrier, or imaging agent in drug delivery systems (DDS) and these efforts are described. Carbon-based NPs, including polymeric, polysaccharide, and lipid NPs as well as carbon dots, have also been widely studied for this purpose and the role they play in DDS for the treatment of liver cancer is illustrated in this review. The multifunctional nature of many NPs described herein, allows these systems to display high anticancer activity in vitro and in vivo and highlights the advantage of and need for combinatorial therapy in treating this difficult cancer. These works are summarized, and future directions are presented for this promising field.
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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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Colloidal and vesicular delivery system for herbal bioactive constituents.
Pandey, R, Bhairam, M, Shukla, SS, Gidwani, B
Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences. 2021;(2):415-438
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Abstract
OBJECTIVES The main objective of the present review is to explore and examine the effectiveness of currently developed novel techniques to resolve the issues which are associated with the herbal constituents/extract. METHODS A systematic thorough search and collection of reviewed information from Science direct, PubMed and Google Scholar databases based on various sets of key phrases have been performed. All the findings from these data have been studied and briefed based on their relevant and irrelevant information. RESULT Herbal drugs are gaining more popularity in the modern world due to their applications in curing various ailments with minimum toxic effects, side effect or adverse effect. However, various challenges exist with herbal extracts/plant actives such as poor solubility (water/lipid), poor permeation, lack of targeting specificity, instability in highly acidic pH, and liver metabolism, etc. Nowadays with the expansion in the technology, novel drug delivery system provides avenues and newer opportunity towards the delivery of herbal drugs with improved physical chemical properties, pharmacokinetic and pharmacodynamic. Developing nano-strategies like Polymeric nanoparticles, Liposomes, Niosomes, Microspheres, Phytosomes, Nanoemulsion and Self Nano Emulsifying Drug Delivery System, etc. imparts benefits for delivery of phyto formulation and herbal bioactives. Nano formulation of phytoconstituents/ herbal extract could lead to enhancement of aqueous solubility, dissolution, bioavailability, stability, reduce toxicity, permeation, sustained delivery, protection from enzymatic degradation, etc. CONCLUSION Based on the above findings, the conclusion can be drawn that the nano sized novel drug delivery systems of herbal and herbal bioactives have a potential future for upgrading the pharmacological action and defeating or overcoming the issues related with these constituents. The aims of the present review was to summarize and critically analyze the recent development of nano sized strategies for promising phytochemicals delivery systems along with their therapeutic applications supported by experimental evidence and discussing the opportunities for further aspects.
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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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End-of-Study Results for the Ladder Phase 2 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration.
Khanani, AM, Callanan, D, Dreyer, R, Chen, S, Howard, JG, Hopkins, JJ, Lin, CY, Lorenz-Candlin, M, Makadia, S, Patel, S, et al
Ophthalmology. Retina. 2021;(8):775-787
Abstract
PURPOSE To report the end-of-study results from the Ladder clinical trial of the Port Delivery System with ranibizumab (PDS) for the treatment of neovascular age-related macular degeneration (nAMD). DESIGN Multicenter, randomized, active treatment-controlled phase 2 clinical trial. PARTICIPANTS Patients diagnosed with nAMD with a documented response to anti-vascular endothelial growth factor treatment who received study treatment (N = 220). METHODS Patients were randomized 3:3:3:2 to treatment with the PDS filled with ranibizumab 10-mg/ml, 40-mg/ml, and 100-mg/ml formulations or monthly intravitreal ranibizumab 0.5-mg injections. MAIN OUTCOME MEASURES End-of-study results for the time to first meeting refill criteria (first refill), mean change from baseline for best-corrected visual acuity (BCVA) and central foveal thickness (CFT), and safety. RESULTS At study end, the mean time on study was 22.1 months (range, 10.8-37.6 months) for all PDS patients. Median time to first refill was 8.7 months, 13.0 months, and 15.8 months, and 28.9%, 56.0%, and 59.4% of patients went 12 months or longer without meeting refill criteria in the PDS 10-mg/ml, 40-mg/ml, and 100-mg/ml treatment arms, respectively. At month 22, the observed mean BCVA change from baseline was ‒4.6 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, ‒2.3 ETDRS letters, +2.9 ETDRS letters, and +2.7 ETDRS letters in the PDS 10-mg/ml, 40-mg/ml, 100-mg/ml, and monthly intravitreal ranibizumab 0.5-mg treatment arms, respectively. At month 22, the observed mean CFT change from baseline was similar in the PDS 100-mg/ml and monthly intravitreal ranibizumab 0.5-mg treatment arms. No new safety signals were detected during the additional follow-up. CONCLUSIONS Over a mean of 22 months on study, vision and anatomic outcomes were comparable between the PDS 100-mg/ml and monthly intravitreal ranibizumab 0.5-mg arms, with a lower total number of ranibizumab treatments with the PDS. The Ladder end-of-study findings were consistent with the primary analysis, and the PDS generally was well tolerated throughout the entire study period. The PDS has the potential to reduce treatment burden in patients with nAMD while maintaining vision.