Pharmaceutical Applications of Biomass Polymers: Review of Current Research and Perspectives.

Polymers derived from natural biomass have emerged as a valuable resource in the field of biomedicine due to their versatility. Polysaccharides, peptides, proteins, and lignin have demonstrated promising results in various applications, including drug delivery design. However, several challenges need to be addressed to realize the full potential of these polymers. The current paper provides a comprehensive overview of the latest research and perspectives in this area, with a particular focus on developing effective methods and efficient drug delivery systems. This review aims to offer insights into the opportunities and challenges associated with the use of natural polymers in biomedicine and to provide a roadmap for future research in this field.

Microbiota-Accessible Boron-Containing Compounds in Complex Regional Pain Syndrome.

The microbiota-gut-brain axis has garnered increasing attention in recent years for its role in various health conditions, including neuroinflammatory disorders like complex regional pain syndrome (CRPS). CRPS is a debilitating condition characterized by chronic neuropathic pain, and its etiology and pathophysiology remain elusive. Emerging research suggests that alterations in the gut microbiota composition and function could play a significant role in CRPS development and progression. Our paper explores the implications of microbiota in CRPS and the potential therapeutic role of boron (B). Studies have demonstrated that individuals with CRPS often exhibit dysbiosis, with imbalances in beneficial and pathogenic gut bacteria. Dysbiosis can lead to increased gut permeability and systemic inflammation, contributing to the chronic pain experienced in CRPS. B, an essential trace element, has shown promise in modulating the gut microbiome positively and exerting anti-inflammatory effects. Recent preclinical and clinical studies suggest that B supplementation may alleviate neuropathic pain and improve CRPS symptoms by restoring microbiota balance and reducing inflammation. Our review highlights the complex interplay between microbiota, inflammation, and neuropathic pain in CRPS and underscores the potential of B as a novel therapeutic approach to target the microbiota-gut-brain axis, offering hope for improved management of this challenging condition.

Nicotinamide Riboside, a Promising Vitamin B3 Derivative for Healthy Aging and Longevity: Current Research and Perspectives.

Many studies have suggested that the oxidized form of nicotinamide adenine dinucleotide (NAD+) is involved in an extensive spectrum of human pathologies, including neurodegenerative disorders, cardiomyopathy, obesity, and diabetes. Further, healthy aging and longevity appear to be closely related to NAD+ and its related metabolites, including nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). As a dietary supplement, NR appears to be well tolerated, having better pharmacodynamics and greater potency. Unfortunately, NR is a reactive molecule, often unstable during its manufacturing, transport, and storage. Recently, work related to prebiotic chemistry discovered that NR borate is considerably more stable than NR itself. However, immediately upon consumption, the borate dissociates from the NR borate and is lost in the body through dilution and binding to other species, notably carbohydrates such as fructose and glucose. The NR left behind is expected to behave pharmacologically in ways identical to NR itself. This review provides a comprehensive summary (through Q1 of 2023) of the literature that makes the case for the consumption of NR as a dietary supplement. It then summarizes the challenges of delivering quality NR to consumers using standard synthesis, manufacture, shipping, and storage approaches. It concludes by outlining the advantages of NR borate in these processes.

Zinc-Boron Complex-Based Dietary Supplements for Longevity and Healthy Life.

The nutritional role of zinc (Zn) and boron (B) in the plant-animal-human food chain is highly topical worldwide research. Our data indicated that Zn-B complex (ZBC)-based dietary supplements can be used as stable non-toxic formulations, with high intestinal absorption rate, inducing alpha2-macroglobulin (A2M) expression for longevity and healthy life. ZBC is metabolized by hydrolysis, mainly at the absorption site (intestinal level), and most of it is excreted in the urine. Within seven hours from the administration in mice, almost the entire amount of orally absorbed ZBC is eliminated in a metabolized form. The highest amount of A2M protein in mouse liver was determined by immunoabsorbance assay in the chronic experiment (1000mg/kg of ZBC), followed by the subchronic experiment (at the same dose of ZBC), and by the acute experiment (5000mg/kg of ZBC).

Zinc-Boron-PLGA biocomposite material: preparation, structural characterization, and in vitro assessment.

Nowadays, the state-of-the-art discoveries in the field of delivery systems for therapeutic purposes have redefined the importance of biocompatible and biodegradable poly(lactic-co-glycolic acid (PLGA) nanocomposites. The study aimed to obtain a biocomposite material, with improved properties of its constituents [zinc-boron (Zn-B) complex and PLGA], by a simple, cost-effective method. The water∕oil∕water double emulsion technique allowed the adjustment of the synthesis parameters, to maximize the degree of Zn-B complex encapsulation. The morphological aspects of the samples were established by scanning electron microscopy (SEM). Particle size distribution was determined by dynamic light scattering (DLS). Morphology was typical for PLGA, spherical one. Depending on the synthesis conditions, the obtained particles have diameters between 10-450 nm. Zeta potential (ZP) showed that the particles have electronegative surface charge, offering a favorable perspective on aggregation, flocculation, and dispersion phenomena. It was observed, applying the design of experiments, that the particles size increased with increasing amounts of PLGA and polyvinyl alcohol (PVA), while ZP increased with higher PLGA and smaller PVA amounts in the formulation. The encapsulation efficiency was determined by ultra-high performance liquid chromatography∕mass spectrometry (UHPLC∕MS). The in vitro assessment was performed using Vero CCL-81 epithelial cell line and the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Zn-B-PLGA biocomposite has promising characteristics and can be used for future biomedical applications.

Influence of Polymer Shell Molecular Weight on Functionalized Iron Oxide Nanoparticles Morphology and In Vivo Biodistribution.

Iron oxide nanoparticles (IONPs) have been extensively used in different biomedical applications due to their biocompatibility and magnetic properties. However, different functionalization approaches have been developed to improve their time-life in the systemic circulation. Here, we have synthesized IONPs using a modified Massart method and functionalized them in situ with polyethylene glycol with different molecular weights (20 K and 35 K). The resulting nanoparticles were characterized in terms of morphology, structure, and composition using transmission electron microscopy (TEM) and selected area electron diffraction (SAED). In vivo biodistribution was evaluated in Balb/c mice, the presence of IONP being evidenced through histopathological investigations. IONP morphological characterization showed a change in shape (from spherical to rhombic) and size with molecular weight, while structural characterization proved the obtaining of highly crystalline samples of spinel structured cubic face-centered magnetite. In vivo biodistribution in a mice model proved the biocompatibility of all of the IONP samples. All NPs were cleared through the liver, spleen, and lungs, while bare IONPs were also evidenced in kidneys.

New Insights into Boron Essentiality in Humans and Animals.

Boron (B) is considered a prebiotic chemical element with a role in both the origin and evolution of life, as well as an essential micronutrient for some bacteria, plants, fungi, and algae. B has beneficial effects on the biological functions of humans and animals, such as reproduction, growth, calcium metabolism, bone formation, energy metabolism, immunity, and brain function. Naturally organic B (NOB) species may become promising novel prebiotic candidates. NOB-containing compounds have been shown to be essential for the symbiosis between organisms from different kingdoms. New insights into the key role of NOB species in the symbiosis between human/animal hosts and their microbiota will influence the use of natural B-based colon-targeting nutraceuticals. The mechanism of action (MoA) of NOB species is related to the B signaling molecule (autoinducer-2-borate (AI-2B)) as well as the fortification of the colonic mucus gel layer with NOB species from B-rich prebiotic diets. Both the microbiota and the colonic mucus gel layer can become NOB targets. This paper reviews the evidence supporting the essentiality of the NOB species in the symbiosis between the microbiota and the human/animal hosts, with the stated aim of highlighting the MoA and targets of these species.

Boron-containing compounds in Dentistry: a narrative review.

Research on the use of boron (B) in the field of oral health has gained momentum in recent years, with various studies on the possibilities of using various B-containing compounds (BCCs). A multitude of applications have been discovered, from cariostatic activity to anti-inflammatory and antifungal activity, paving the way for other new research directions. B is a microelement that is commonly found in the human diet, and present throughout the body, with the highest concentration in the structure of bones, teeth, and gastrointestinal mucus gel layer. Multiple studies have demonstrated that B plays some important roles, especially in bone development and recently has been proposed to have an essential role in the healthy symbiosis. In addition, B has also attracted the interest of researchers, as various studies used BCCs in conventional or modern biomaterials. In this review, we have brought together the information we have found about B updates in the dental field and analyzing its future perspectives and potential for further studies.

Nanoparticle-functionalized dressings for the treatment of third-degree skin burns - histopathological and immunohistochemical study.

Skin burns are one of the most common injuries associated with increased morbidity and mortality, especially in the children and the elderlies. Severe burns, especially, result in a systemic immune and inflammatory response, which may reflect in multiple organ insufficiency, and a fast and effective local restorative process is essential for functionality recovering, as well as for interrupting the generalized systemic response. We have aimed here to assess the effect of different wound dressings in what it regards the morphology and clinical restoration after a skin burn. On a rat animal model, we have evaluated the macroscopic and histopathological features of controlled third degree skin burns in control animals versus treatments with local dressings of silver sulfadiazine (SDA) cream, simple gel (G), gel + silver nanoparticles (AgNPs) (G+NPS), gel + exosomes (G+EXO) and gel + AgNPs + exosomes (Gel+NPS+EXO), at 14 days and, respectively, 21 days after the lesion. Tissue fragments were harvested and processed for histopathology and immunohistochemistry. Immunofluorescence was utilized to evaluate the maturity of underlaying granulation tissue based on double stainings for smooth muscle actin (SMA) and cluster of differentiation 31 (CD31). Our study showed variability in what it regards the vessel density and immunoexpression of SMA between the treatments, and image analysis revealed that most SMA reduction and blood vessel density reduction in the maturing granulation tissue occurred for the G+NPS and G+NPS+EXO treatments. A complete re-epithelization was also observed for the G+NPS+EXO treatment. Overall, our results show that improved topic treatments promote faster re-epithelization and reparation of the dermis after skin burn lesions, providing thus an avenue for new treatments that aim both local recuperation and systemic infection prevention.

Preclinical and histological study of boron-containing compounds hydrogels on experimental model of periodontal disease.

Periodontitis is a disease that affects a wide group of people, and there has been an increased interest in the research of finding useful materials that help reduce inflammation and the further loss of tissue. In this study, we have tested a boron-containing compound (BCC) Calcium Fructoborate (CaFB) and Boric Acid (BA) hydrogels on the gingival level on Wistar rats. First, we have induced the periodontal disease at the lower incisors, we have applied the hydrogels and after a week, we have euthanized the rats. Next, the oral soft tissue reaction was clinically and then histologically investigated. Our study has shown good clinical response of the oral tissue, and we have noticed lower levels of inflammation on the experimental groups treated with the BCCs hydrogels. Despite the generally good response of the biological structures to the presence of BA and CaFB on periodontal level, more scientifically proved information is needed to obtain the desired biological responses in all clinical situations.

Biofilm-Resistant Nanocoatings Based on ZnO Nanoparticles and Linalool.

Biofilms represent an increasing challenge in the medical practice worldwide, imposing a serious threat to public health. As bacterial strains have developed antibiotic resistance, researcher's attention has been extensively focused on developing more efficient antimicrobial strategies. In this context, the present study reports the synthesis, physicochemical characterization, ex vivo biodistribution, and in vitro evaluation of the capacity of nanostructured surfaces based on zinc oxide (ZnO) and biologically active molecules to modulate clinically relevant microbial biofilms. ZnO nanoparticles (NPs) were synthesized through a co-precipitation method without thermal treatment. The matrix-assisted pulsed laser evaporation (MAPLE) was applied for preparing nanostructured coatings based on ZnO NPs surface modified with linalool that were further characterized by X-ray diffraction (XRD), thermogravimetric analysis with differential scanning calorimetry (TGA-DSC), scanning electron microscopy (SEM), transmission electron microscopy with selected area electron diffraction (TEM-SAED), Fourier-transform infrared spectroscopy (FT-IR), and infrared microscopy (IRM). Histological analyses carried out at 7 days and 14 days after the intraperitoneal administration of linalool modified ZnO NPs revealed the absence of the latter from the brain, kidney, liver, lung, myocardium, and pancreas. Through in vitro assays on prokaryotic cells, it was proven that ZnO coatings hinder microbial biofilm formation of both Gram-positive and Gram-negative bacteria strains.

The Effect of Silver Nanoparticles on Antioxidant/Pro-Oxidant Balance in a Murine Model.

This study aimed to evaluate the subacute effect of two types of Ag-NPs(EG-AgNPs and PVP-EG-AgNPs) on antioxidant/pro-oxidant balance in rats. Seventy Wistar rats (35 males and 35 females) were divided in 7 groups and intraperitoneally exposed for 28 days to 0, 1, 2 and 4 mg/kg bw/day EG-Ag-NPs and 1, 2 and 4 mg/kg bw/day PVP- EG-Ag-NPs. After 28 days, the blood was collected, and the total antioxidant capacity (TAC), thiobarbituric reactive species (TBARS),protein carbonyl (PROTC) levels, reduced glutathione (GSH) levels and catalase (CAT) activity were determined. EG-Ag-NPs determined protective antioxidant effects in a dose-dependent manner. The exposure to the 4 mg/kg bw/day EG-Ag-NPs determines both in males and females a significant increase in TAC and CAT and a significant decrease in TBARS and PROTC only in females. The PVP-EG-AgNPs showed a different trend compared to EG-AgNPs. At 4 mg/kg bw/day the PVP-EG-AgNPs induce increased PROTC levels and decreased GSH (males and females) and TAC levels (males). The different mechanisms of EG-AgNPs and PVP-EG-AgNPs on antioxidant-/pro-oxidant balance can be explained by the influence of coating agent used for the preparation of the nanoparticles in the formation and composition of protein corona that influence their pathophysiology in the organism.

Biodistribution of essential oil-conjugated silver nanoparticles.

The beneficial synergy between antimicrobial silver nanoparticles (AgNPs) and essential oils (EOs), with therapeutic effects that have been acknowledged and explored for a long time, opens the way towards developing new and promising alternatives for anti-infective therapies. With the aim to improve the cytocompatibility and stability of AgNPs and to overcome the volatilization of EOs, AgNPs conjugated with sage (Salvia officinalis) and cinnamon (Cinnamomum aromaticum) EOs were obtained in our study. The synthesis process was realized either by classical or ultrasound-assisted chemical reduction. Compositional and microstructural characterization of the as-obtained Ag@EO NPs was performed by X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The biodistribution of Ag@EO NPs was evaluated on a mouse animal model.

Natural and semisynthetic candidate molecules for COVID-19 prophylaxis and treatment.

Coronaviruses (CoVs) represent a family of viruses that have numerous animal hosts, and they cause severe respiratory, as well as systemic and enteric infections, in humans. Currently, there are limited antiviral strategies for treating patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The lack of specific antiviral medicines and SARS-CoV-2 vaccines continues to aggravate the situation. Natural product-based antiviral drugs have been used in the two previous CoV outbreaks: Middle East respiratory syndrome coronavirus (MERS-CoV) and the first SARS-CoV. This review emphasizes the role of natural and semisynthetic candidate molecules for coronavirus disease 2019 (COVID-19) prophylaxis and treatment. The experimental evidence suggests that nature could offer huge possibilities for treatment of the COVID-19 pandemic.

In vitro and in vivo studies of novel fabricated bioactive dressings based on collagen and zinc oxide 3D scaffolds.

The paper reports the synthesis and physico-chemical and biological characterization of novel wound dressings based on collagen and essential oil functionalized ZnO nanoparticles intended to improve the treatment of burns and to reduce the risk for developing wound sepsis in patients with burns or chronic wounds. The prepared wound dressings were physico-chemical characterized by Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). In vitro biocompatibility and cytotoxicity was proved on human fibroblast cells, antimicrobial potential was assessed on Gram positive and Gram negative bacteria models (Staphylococcus aureus and Escherichia coli, respectively), while in vivo studies were performed on a rat burn wound experimental model. Functionalized ZnO nanoparticles (NPs) proved to range 15-20 nm in size and contain about 1% orange essential oil (EO), which was utilized as a natural antimicrobial agent. NPs are grain-shapped and have a low tendency to form aggregates. No toxicity was noticed in vitro, as human fibroblasts maintained a normal growth and their membrane integrity in the presence of EO functionalized NPs. The capacity of the prepared wound dressings to act as implantable bioresorbable scaffolds that accelerates wounds healing along with an excellent biocompatibility, lack of cytotoxicity and a good antibacterial activity, make these materials promising and safe candidates for wound dressing, especially in burn patients.

The Fructoborates: Part of a Family of Naturally Occurring Sugar-Borate Complexes-Biochemistry, Physiology, and Impact on Human Health: a Review.

Sugar-borates (SBs) are mono- or di-sugar-borate esters (SBEs) comprised of one or two monosaccharide molecules linked to a boron (B) atom. SBEs occur naturally in commonly consumed herbs, vegetables, fruits, seeds, and nuts and, other than greatly varying levels of B found in local drinking water, are the primary natural dietary sources of B-containing molecules in humans. To date, the most studied SBE is calcium fructoborate (CaFB). CaFB represents an important example of how organic B-containing molecules are significantly distinct from their inorganic counterparts. During these past two decades, CaFB has been researched for its physical and biochemical characteristics, safety, and clinical outcomes. Results of these researches are presented and discussed herein. CaFB has been characterized using Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), high-performance thin-layer chromatography (HPTLC), nuclear magnetic resonance (NMR), liquid chromatography-multistage accurate mass spectrometry (LC-MSn), X-ray diffraction (XRD), Raman spectroscopy, and inductively coupled plasma (ICP) in non-biological and biological specimens. Potential health benefits of CaFB have been clinically investigated in pilot and efficacy studies demonstrating (i) significant reductions in knee discomfort and improved flexibility within 7, 14, and 90 days and (ii) significant effect on blood levels of inflammatory, cardiovascular, and other biomarkers. These studies support the use of CaFB as a dietary supplement for the management of joint discomfort. CaFB is presented here in order to illustrate how physiological benefits are imparted by distinct organic boron-containing molecules rather than solely by the element B itself. Considering recent National Health and Nutrition Examination Survey (NHANES) data reporting increases in age-related joint pain and an increasing elderly demographic, SBEs offer potential for safe, natural, and effective management of joint discomfort and improved mobility in human and animal health applications. Several of these studies may also open new opportunities for use of SBEs for health benefits beyond joint health.

Study of antimicrobial effects of functionalized silver nanoparticles.

In recent decades, the study of nanoparticles (NPs) has gained a great scientific interest, due to a wide range of potential applications, in different fields: electronic, optical and biomedical. Some of the most studied effects of NPs are antibacterial ones, because the large, sometimes unjustified and uncontrolled administration of antibiotics has led to the emergence of multidrug-resistant (MDR) bacterial strains. In our study, starting from silver nitrate (AgNO3), we made approximately 30 nm spherical AgNPs that were coated with a thin layer of ethylene glycol (EG) or EG and polyvinylpyrrolidone (PVP). The microbial culture study showed that AgNPs have antibacterial effects, depending on the dose of the NPs and the type of bacteria.

Antibiofilm Coatings Based on PLGA and Nanostructured Cefepime-Functionalized Magnetite.

The aim of our study was to obtain and evaluate the properties of polymeric coatings based on poly(lactic-co-glycolic) acid (PLGA) embedded with magnetite nanoparticles functionalized with commercial antimicrobial drugs. In this respect, we firstly synthesized the iron oxide particles functionalized (@) with the antibiotic Cefepime (Fe3O4@CEF). In terms of composition and microstructure, the as-obtained powdery sample was investigated by means of grazing incidence X-ray diffraction (GIXRD), thermogravimetric analysis (TGA), scanning and transmission electron microscopy (SEM and TEM, respectively). Crystalline and nanosized particles (~5 nm mean particle size) with spherical morphology, consisting in magnetite core and coated with a uniform and reduced amount of antibiotic shell, were thus obtained. In vivo biodistribution studies revealed the obtained nanoparticles have a very low affinity for innate immune-related vital organs. Composite uniform and thin coatings based on poly(lactide-co-glycolide) (PLGA) and antibiotic-functionalized magnetite nanoparticles (PLGA/Fe3O4@CEF) were subsequently obtained by using the matrix assisted pulsed laser evaporation (MAPLE) technique. Relevant compositional and structural features regarding the composite coatings were obtained by performing infrared microscopy (IRM) and SEM investigations. The efficiency of the biocompatible composite coatings against biofilm development was assessed for both Gram-negative and Gram-positive pathogens. The PLGA/Fe3O4@CEF materials proved significant and sustained anti-biofilm activity against staphylococcal and Escherichia coli colonisation.

Antibiotic Resistance and Virulence Phenotypes of Recent Bacterial Strains Isolated from Urinary Tract Infections in Elderly Patients with Prostatic Disease.

Acute bacterial prostatitis is one of the frequent complications of urinary tract infection (UTI). From the approximately 10% of men having prostatitis, 7% experience a bacterial prostatitis. The purpose of this study was to investigate the prevalence of uropathogens associated with UTIs in older patients with benign prostatic hyperplasia and to assess their susceptibility to commonly prescribed antibiotics as well as the relationships between microbial virulence and resistance features. Uropathogenic Escherichia coli was found to be the most frequent bacterial strain isolated from patients with benign prostatic hyperplasia, followed by Enterococcus spp., Enterobacter spp., Klebsiella spp., Proteus spp., Pseudomonas aeruginosa, and Serratia marcescens. Increased resistance rates to tetracyclines, quinolones, and sulfonamides were registered. Besides their resistance profiles, the uropathogenic isolates produced various virulence factors with possible implications in the pathogenesis process. The great majority of the uropathogenic isolates revealed a high capacity to adhere to HEp-2 cell monolayer in vitro, mostly exhibiting a localized adherence pattern. Differences in the repertoire of soluble virulence factors that can affect bacterial growth and persistence within the urinary tract were detected. The Gram-negative strains produced pore-forming toxins-such as hemolysins, lecithinases, and lipases-proteases, siderophore-like molecules resulted from the esculin hydrolysis and amylases, while Enterococcus sp. strains were positive only for caseinase and esculin hydrolase. Our study demonstrates that necessity of investigating the etiology and local resistance patterns of uropathogenic organisms, which is crucial for determining appropriate empirical antibiotic treatment in elderly patients with UTI, while establishing correlations between resistance and virulence profiles could provide valuable input about the clinical evolution and recurrence rates of UTI.