High-Molecular-Weight Dextran-Type Exopolysaccharide Produced by the Novel Apilactobacillus waqarii Improves Metabolic Syndrome: In Vitro and In Vivo Analyses.

Metabolic syndrome is a leading medical concern that affects one billion people worldwide. Metabolic syndrome is defined by a clustering of risk factors that predispose an individual to cardiovascular disease, diabetes and stroke. In recent years, the apparent role of the gut microbiota in metabolic syndrome has drawn attention to microbiome-engineered therapeutics. Specifically, lactic acid bacteria (LAB) harbors beneficial metabolic characteristics, including the production of exopolysaccharides and other microbial byproducts. We recently isolated a novel fructophilic lactic acid bacterium (FLAB), Apilactobacillus waqarii strain HBW1, from honeybee gut and found it produces a dextran-type exopolysaccharide (EPS). The objective of this study was to explore the therapeutic potential of the new dextran in relation to metabolic syndrome. Findings revealed the dextran's ability to improve the viability of damaged HT-29 intestinal epithelial cells and exhibit antioxidant properties. In vivo analyses demonstrated reductions in body weight gain and serum cholesterol levels in mice supplemented with the dextran, compared to control (5% and 17.2%, respectively). Additionally, blood glucose levels decreased by 16.26% following dextran supplementation, while increasing by 15.2% in non-treated mice. Overall, this study displays biotherapeutic potential of a novel EPS to improve metabolic syndrome and its individual components, warranting further investigation.

Nanotechnology in development of next generation of stent and related medical devices: Current and future aspects.

Coronary stents have saved millions of lives in the last three decades by treating atherosclerosis especially, by preventing plaque protrusion and subsequent aneurysms. They attenuate the vascular SMC proliferation and promote reconstruction of the endothelial bed to ensure superior revascularization. With the evolution of modern stent types, nanotechnology has become an integral part of stent technology. Nanocoating and nanosurface fabrication on metallic and polymeric stents have improved their drug loading capacity as well as other mechanical, physico-chemical, and biological properties. Nanofeatures can mimic the natural nanofeatures of vascular tissue and control drug-delivery. This review will highlight the role of nanotechnology in addressing the challenges of coronary stents and the recent advancements in the field of related medical devices. Different generations of stents carrying nanoparticle-based formulations like liposomes, lipid-polymer hybrid NPs, polymeric micelles, and dendrimers are discussed highlighting their roles in local drug delivery and anti-restenotic properties. Drug nanoparticles like Paclitaxel embedded in metal stents are discussed as a feature of first-generation drug-eluting stents. Customized precision stents ensure safe delivery of nanoparticle-mediated genes or concerted transfer of gene, drug, and/or bioactive molecules like antibodies, gene mimics via nanofabricated stents. Nanotechnology can aid such therapies for drug delivery successfully due to its easy scale-up possibilities. However, limitations of this technology such as their potential cytotoxic effects associated with nanoparticle delivery that can trigger hypersensitivity reactions have also been discussed in this review. This article is categorized under: Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Probiotics, prebiotics, synbiotics and other microbiome-based innovative therapeutics to mitigate obesity and enhance longevity via the gut-brain axis.

The global prevalence of obesity currently exceeds 1 billion people and is accompanied by an increase in the aging population. Obesity and aging share many hallmarks and are leading risk factors for cardiometabolic disease and premature death. Current anti-obesity and pro-longevity pharmacotherapies are limited by side effects, warranting the development of novel therapies. The gut microbiota plays a major role in human health and disease, with a dysbiotic composition evident in obese and aged individuals. The bidirectional communication system between the gut and the central nervous system, known as the gut-brain axis, may link obesity to unhealthy aging. Modulating the gut with microbiome-targeted therapies, such as biotics, is a novel strategy to treat and/or manage obesity and promote longevity. Biotics represent material derived from living or once-living organisms, many of which have therapeutic effects. Pre-, pro-, syn- and post-biotics may beneficially modulate gut microbial composition and function to improve obesity and the aging process. However, the investigation of biotics as next-generation therapeutics has only just begun. Further research is needed to identify therapeutic biotics and understand their mechanisms of action. Investigating the function of the gut-brain axis in obesity and aging may lead to novel therapeutic strategies for obese, aged and comorbid (e.g., sarcopenic obese) patient populations. This review discusses the interrelationship between obesity and aging, with a particular emphasis on the gut microbiome, and presents biotics as novel therapeutic agents for obesity, aging and related disease states.

Colon-Targeted Sustained-Release Combinatorial 5-Fluorouracil and Quercetin poly(lactic-co-glycolic) Acid (PLGA) Nanoparticles Show Enhanced Apoptosis and Minimal Tumor Drug Resistance for Their Potential Use in Colon Cancer.

Colorectal cancer (CRC) is the third most common cancer worldwide, acting as a significant public health problem. 5-Fluorouracil (5-FU) is a key chemotherapy for various types of cancer, due to its broad anticancer activity. However, the emergence of drug resistance is a considerable limitation in the clinical application of 5-FU. Quercetin (QC) is proposed as an adjuvant therapy to minimize drug resistance to chemotherapeutics and enhance their pharmacological efficacy. The oral delivery of 5-FU and QC is challenged by poor aqueous solubility of QC and poor cellular permeability of 5-FU. To solve this issue, novel polylactide-co-glycolide (PLGA) combinatorial nanoparticles loading 5-FU and QC were prepared to deliver them directly to the colon. These sustained-release combinatorial nanoparticles recorded a significant decrease in cancer cell proliferation, C-reactive protein (CRP) level, and Interleukin-8 (IL-8) expression by 30.08%, 40.7%, and 46.6%, respectively. The results revealed that this combination therapy may offer a new strategy for the targeted delivery of chemotherapeutics to the colon.

A comprehensive update of siRNA delivery design strategies for targeted and effective gene silencing in gene therapy and other applications.

INTRODUCTION: RNA interference (RNAi) using small interfering RNA (siRNA) is a promising strategy to control many genetic disorders by targeting the mRNA of underlying genes and degrade it. However, the delivery of siRNA to targeted organs is highly restricted by several intracellular and extracellular barriers. AREAS COVERED: This review discusses various design strategies developed to overcome siRNA delivery obstacles. The applied techniques involve chemical modification, bioconjugation to specific ligands, and carrier-mediated strategies. Nanotechnology-based systems like liposomes, niosomes, solid lipid nanoparticles (SLNs), dendrimers, and polymeric nanoparticles (PNs) are also discussed. EXPERT OPINION: Although the mechanism of siRNA as a gene silencer is well-established, only a few products are available as therapeutics. There is a great need to develop and establish siRNA delivery systems that protects siRNAs and delivers them efficiently to the desired sitesare efficient and capable of targeted delivery. Several diseases are reported to be controlled by siRNA at their early stages. However, their targeted delivery is a daunting challenge.

Controlled and customizable baculovirus NOS3 gene delivery using PVA-based hydrogel systems.

Nitric oxide synthase 3 (NOS3) eluting polyvinyl alcohol-based hydrogels have a large potential in medical applications and device coatings. NOS3 promotes nitric oxide and nitrate production and can effectively be delivered using insect cell viruses, termed baculoviruses. Nitric oxide is known for regulating cell proliferation, promoting blood vessel vasodilation, and inhibiting bacterial growth. The polyvinyl alcohol (PVA)-based hydrogels investigated here sustained baculovirus elution from five to 25 days, depending on the hydrogel composition. The quantity of viable baculovirus loaded significantly declined with each freeze-thaw from one to four (15.3 ± 2.9% vs. 0.9 ± 0.5%, respectively). The addition of gelatin to the hydrogels protected baculovirus viability during the freeze-thaw cycles, resulting in a loading capacity of 94.6 ± 1.2% with sustained elution over 23 days. Adding chitosan, PEG-8000, and gelatin to the hydrogels altered the properties of the hydrogel, including swelling, blood coagulation, and antimicrobial effects, beneficial for different therapeutic applications. Passive absorption of the baculovirus into PVA hydrogels exhibited the highest baculovirus loading (96.4 ± 0.6%) with elution over 25 days. The baculovirus-eluting hydrogels were hemocompatible and non-cytotoxic, with no cell proliferation or viability reduction after incubation. This PVA delivery system provides a method for high loading and sustained release of baculoviruses, sustaining nitric oxide gene delivery. This proof of concept has clinical applications as a medical device or stent coating by delivering therapeutic genes, improving blood compatibility, preventing thrombosis, and preventing infection.

Clinical pharmacology of siRNA therapeutics: current status and future prospects.

INTRODUCTION: Small interfering RNA (siRNA) has emerged as a powerful tool for post-transcriptional downregulation of multiple genes for various therapies. Naked siRNA molecules are surrounded by several barriers that tackle their optimum delivery to target tissues such as limited cellular uptake, short circulation time, degradation by endonucleases, glomerular filtration, and capturing by the reticuloendothelial system (RES). AREAS COVERED: This review provides insights into studies that investigate various siRNA-based therapies, focusing on the mechanism, delivery strategies, bioavailability, pharmacokinetic, and pharmacodynamics of naked and modified siRNA molecules. The clinical pharmacology of currently approved siRNA products is also discussed. EXPERT OPINION: Few siRNA-based products have been approved recently by the Food and Drug Administration (FDA) and other regulatory agencies after approximately 20 years following its discovery due to the associated limitations. The absorption, distribution, metabolism, and excretion of siRNA therapeutics are highly restricted by several obstacles, resulting in rapid clearance of siRNA-based therapeutic products from systemic circulation before reaching the cytosol of targeted cells. The siRNA therapeutics however are very promising in many diseases, including gene therapy and SARS-COV-2 viral infection. The design of suitable delivery vehicles and developing strategies toward better pharmacokinetic parameters may solve the challenges of siRNA therapies.