Ferula latisecta gels for synthesis of zinc/silver binary nanoparticles: antibacterial effects against gram-negative and gram-positive bacteria and physicochemical characteristics.

This study explores the potential antibacterial applications of zinc oxide nanoparticles (ZnO NPs) enhanced with silver (Ag) using plant gel (ZnO-AgO NPs). The problem addressed is the increasing prevalence of pathogenic bacteria and the need for new, effective antimicrobial agents. ZnO NPs possess distinctive physicochemical properties that enable them to selectively target bacterial cells. Their small size and high surface area-to-volume ratio allow efficient cellular uptake and interaction with bacterial cells. In this study, the average size of the synthesized ZnO-Ag nanoparticles was 77.1 nm, with a significant standard deviation of 33.7 nm, indicating a wide size distribution. The nanoparticles demonstrated remarkable antibacterial efficacy against gram-negative and gram-positive bacteria, with inhibition zones of 14.33 mm for E. coli and 15.66 mm for B. subtilis at a concentration of 300 µg/ml. Minimum inhibitory concentrations (MIC) were determined to be 100 µg/ml for E. coli and 75 µg/ml for S. saprophyticus. Additionally, ZnO-Ag NPs exhibited excellent biocompatibility, making them appropriate for various pharmacological uses. This study utilizes Ferula latisecta gels, offering a sustainable and eco-friendly approach to nanoparticle synthesis. Incorporating of Ag into ZnO NPs significantly enhances their antimicrobial properties, with the combined results showing great inhibition effects on pathogenic microbes. The findings suggest that ZnO-Ag NPs could be a promising candidate for addressing the challenges posed by drug-resistant bacterial infections and enhancing antimicrobial treatments.

Investigating the Role of Amino Acids in Short Peptides for Hydroxyapatite Binding and Osteogenic Differentiation of Mesenchymal Stem Cells to Aid Bone Regeneration.

Bone defects show a slow rate of osteoconduction and imperfect reconstruction, and the current treatment strategies to treat bone defects suffer from limitations like immunogenicity, lack of cell adhesion, and the absence of osteogenic activity. In this context, bioactive supramolecular peptides and peptide gels offer unique opportunities to develop biomaterials that can play a dominant role in the biomineralization of bone tissues and promote bone formation. In this article, we have demonstrated the potential of six tetrapeptides for specific binding to hydroxyapatite (HAp), a major inorganic component of the bone, and their effect on the growth and osteogenic differentiation of mesenchymal stem cells (MSCs). We adopted a simplistic approach of rationally designing amphiphilic peptides by incorporating amino acids, Ser, pSer, Pro, Hyp, Asp, and Glu, which are present in either collagenous or noncollagenous proteins and render properties like antioxidant, calcification, and mineralization. A total of six tetrapeptides, Trp-Trp-His-Ser (WWHS), Trp-Trp-His-pSer (WWHJ), Trp-Trp-His-Pro (WWHP), Trp-Trp-His-Hyp (WWHO), Trp-Trp-His-Asp (WWHD), and Trp-Trp-His-Glu (WWHE), were synthesized. Four peptides were found to self-assemble into nanofibrillar gels resembling the extracellular matrix (ECM), and the remaining two peptides (WWHJ, WWHP) self-assembled into nanorods. The peptides showed excellent cell adhesion, encapsulation, proliferation, and migration and induced the differentiation of mesenchymal stem cells (MSCs), as evident from the enhanced mineralization, resulting from the upregulation of osteogenic markers, RUNX 2, COL I, OPN, and OCN, alkaline phosphatase (ALP) production, and calcium deposition. The peptides also induced the downregulation of inflammatory markers, TNF-α and iNOS, and the upregulation of the anti-inflammatory marker, IL-10, resulting in M2 macrophage polarization. RANKL and TRAP genes were downregulated in a coculture system of MC3T3-E1 and RAW 264.7 cells, implying that peptides promote osteogenesis and inhibit osteoclastogenesis. The peptide-based biomaterials developed in this work can enhance bone regeneration capacity and show strong potential as scaffolds for bone tissue engineering.

Molecular nucleation mechanisms and control strategies for crystal polymorph selection.

The formation of condensed (compacted) protein phases is associated with a wide range of human disorders, such as eye cataracts, amyotrophic lateral sclerosis, sickle cell anaemia and Alzheimer's disease. However, condensed protein phases have their uses: as crystals, they are harnessed by structural biologists to elucidate protein structures, or are used as delivery vehicles for pharmaceutical applications. The physiochemical properties of crystals can vary substantially between different forms or structures ('polymorphs') of the same macromolecule, and dictate their usability in a scientific or industrial context. To gain control over an emerging polymorph, one needs a molecular-level understanding of the pathways that lead to the various macroscopic states and of the mechanisms that govern pathway selection. However, it is still not clear how the embryonic seeds of a macromolecular phase are formed, or how these nuclei affect polymorph selection. Here we use time-resolved cryo-transmission electron microscopy to image the nucleation of crystals of the protein glucose isomerase, and to uncover at molecular resolution the nucleation pathways that lead to two crystalline states and one gelled state. We show that polymorph selection takes place at the earliest stages of structure formation and is based on specific building blocks for each space group. Moreover, we demonstrate control over the system by selectively forming desired polymorphs through site-directed mutagenesis, specifically tuning intermolecular bonding or gel seeding. Our results differ from the present picture of protein nucleation, in that we do not identify a metastable dense liquid as the precursor to the crystalline state. Rather, we observe nucleation events that are driven by oriented attachments between subcritical clusters that already exhibit a degree of crystallinity. These insights suggest ways of controlling macromolecular phase transitions, aiding the development of protein-based drug-delivery systems and macromolecular crystallography.

Intranasal administration of innovative triamcinolone acetonide encapsulated cubosomal in situ gel: formulation and characterization.

AIM: The primary objective of the research was to develop a cubosomal in situ gel encapsulated with Triamcinolone acetonide (TCA) in order to enhance its penetration through the blood-brain barrier (BBB) when administered via the intranasal route, thus enabling efficient and rapid action. METHOD: Cubosomes were formulated by top-down approach using glyceryl monooleate (GMO), using pluronics127 (PF127) and polyvinyl alcohol (PVA) in varying proportions based on the Box-Behnken design. High resolution transmission electron microscopy (HR-TEM) analysis confirmed the morphology of the cubosomes. The in situ gel was formulated and optimized. Experiments involving ex vivo permeation and histopathology analyses were undertaken to evaluate drug permeation and tissue effects. RESULTS: The cubosomes exhibited a particle size (PS) of 197.9 nm, zeta potential (ZP) of -31.11 mV, and entrapment efficacy (EE) of 84.31%, with low deviation. Batch F4 (19% PF127) showed favorable results. In vitro and ex vivo permeation studies revealed drug release of 78.59% and 76.65%, respectively, after 8 h. Drug release followed the Hixson Crowell model of release kinetics. The histopathological examination revealed no signs of toxicity or adverse effects on the nasal mucosa of the sheep. The formulation exhibited short-term stability, maintaining its integrity and properties when stored at room temperature. CONCLUSION: The utilization of an intranasal cubosomal in situ gel encapsulated with TCA was anticipated to lower intracranial pressure and improve patient adherence by offering effective relief for individuals suffering from Brain edema. This efficacy is attributed to its rapid onset of action and its safe and well-tolerated dosage form.

Formulation development and evaluation of nasal in situ gel of promethazine hydrochloride.

OBJECTIVE: The present work aims to develop mucoadhesive thermosensitive nasal in situ gel for Promethazine hydrochloride using quality by design (QbD) approach. It can reduce nasal mucociliary clearance (MCC) and increase residence of the drug on nasal mucosa. This might increase drug absorption to improve bioavailability of the drug as compared to oral dosage form. SIGNIFICANCE: Promethazine hydrochloride is an antiemetic drug administered by oral, parenteral and rectal routes. These routes have poor patient compliance or low bioavailability. Nasal route is a better alternative as it has large surface area, high drug absorption rate and no first pass effect. Its only limitation is short drug retention time due to MCC. By formulating a mucoadhesive in situ gel, the MCC can be reduced, and drug absorption will be prolonged. Thus, improving bioavailability. METHOD: In-situ gel was prepared by cold method having material attributes as concentration of Poloxamer 407 (X1) as gelling agent and hydroxypropyl methyl cellulose K4M (X2) as mucoadhesive agent. Critical Quality Attributes (CQA) were gelation temperature, mucoadhesive force and ex-vivo diffusion. Central composite design (CCD) was adopted for optimization. RESULT: Optimized formulation satisfied all the CQA significant for nasal administration. Moreover, the formulation was found to be stable in accelerated stability studies for 3 months. CONCLUSION: It can be concluded that since the drug can easily permeate through nasal mucosa and can gain access directly in the brain without undergoing first pass metabolism along with increased residence due to mucoadhesion, mucoadhesive in situ gel has potential to increase drug bioavailability.

Assembly of In-Situ Gel Containing Nano-Spanlastics of an Angiotensin II Inhibitor as a Novel Epitome for Hypertension Management: Factorial Design Optimization, In-vitro Gauging, Pharmacokinetics, and Pharmacodynamics Appraisal.

More than 1 billion people worldwide suffer from hypertension; therefore, hypertension management has been categorized as a global health priority. Losartan potassium (LP) is an antihypertensive drug with a limited oral bioavailability of about 33% since it undergoes the initial metabolic cycle. Thus, nasal administration is a unique route to overcome first-pass metabolism. The investigation focused on the potential effects of LP-loaded spanlastic vesicles (SNVs) on LP pharmacodynamics and pharmacokinetic parameters, utilizing a thin-film hydration methodology established on a 3122 full factorial design. Entrapment efficiency (EE%) ranged from 39.8 ± 3.87.8 to 83.8 ± 2.92% for LP-SNVs. Vesicle size (VS) varied from 205.5 ± 6.5.10 to 445.1 ± 13.52 nm, and the percentage of LP released after 8 h (Q8h) ranged from 30.8 ± 3.10 to 68.8 ± 1.45%. LP permeated through the nasal mucosa during 24 h and flocculated from 194.1 ± 4.90 to 435.3 ± 13.53 µg/cm2. After twenty-four hours, the optimal LP-SNVs in-situ gel showed 2.35 times more permeation through the nasal mucosa than the LP solution. It also lowered systolic blood pressure, so it is thought to be better than the reference formulation in terms of pharmacodynamics. The pharmacokinetics studies demonstrated that the intranasal LP-SNVs gel boosted its bioavailability approximately 6.36 times compared to the oral LP solution. Our research showed that intranasal LP-SNVs could be a good nanoplatform because they are well-tolerated and have possible pharmacokinetics and pharmacodynamics.

A New Method for Obtaining Monospecies and Binary Cultures of Staphylococcus spp. in Alginate Gel and the Study of the Action of Active Compounds on These Cultures on the Example of Catecholamines.

A simple and efficient method for obtaining monospecies and binary Staphylococcus aureus and Staphylococcus epidermidis cultures in sodium alginate gel matrix mimicking the natural microenvironment of the nasal cavity was proposed. The cultures were used for studying the effect of norepinephrine on monospecies and binary communities of two types of bacteria, S. aureus (invasive strain) and S. epidermis (commensal strain). After 24-h incubation, S. aureus predominated in the binary community, but later it was replaced by S. epidermis. Norepinephrine at higher concentrations accelerated this process without principally changing it. The model can be used to develop more effective complex antimicrobial drugs.

Beneficial Effect of Polysaccharide Gel Made of Xanthan Gum and Locust Bean Gum on Bovine Oocytes.

The present study examined the effect of polysaccharides gels made of xanthan gum and locust bean gum (gel culture system) on oocyte maturation and explored the molecules causing the beneficial effect of the gel culture system. Oocytes and cumulus cells complexes were collected from slaughterhouse-derived ovaries and cultured on a plastic plate or gel. The gel culture system improved the rate of development to the blastocyst stage. The oocytes that matured on the gel contained high lipid contents and F-actin formation, and the resultant 8-cell stage embryos had low DNA methylation levels compared to their plate counterparts. RNA sequencing of the oocytes and embryos revealed the differentially expressed genes between the gel and plate culture systems, and upstream regulator analysis revealed estradiol and TGFB1 as top activated upstream molecules. The medium of the gel culture system contained higher concentrations of estradiol and TGFB1 than that of the plate cultures system. Supplementation of the maturation medium with either estradiol or TGFB1 resulted in high lipid content in oocytes. In addition, TGFB1 improved the developmental ability of the oocytes and increased F-actin content while reducing DNA methylation levels in the 8-cell stage embryos. In conclusion, the gel culture system is useful for embryo production, potentially through the upregulation of TGFB1.

Use of topical morphine gel in epidermolysis bullosa wounds-A series of case studies.

In recent years, the use of topical morphine gel has increased in the palliative care setting to reduce pain in chronic wounds and fungating tumours. However, there is a paucity of evidence to support its effectiveness. Epidermolysis bullosa (EB) is a rare genetic skin fragility disorder characterised by painful chronic wounds. Adequate control of wound pain can be challenging in this patient group due to other complexities associated with the more severe sub-types of the disease. Topical morphine gel has been used as an adjunct therapy in a small number of EB patients in our tertiary centre in an attempt to improve pain control and quality of life. The purpose of this paper is to demonstrate the efficacy of topical morphine gel used in a variety of EB wounds as well as patient reported reduction in pain through a series of case studies. The case studies suggest a positive effect of topical morphine gel on painful wounds across a spectrum of EB subtypes.

Microneedle-Mediated Permeation Enhancement of Chlorhexidine Digluconate: Mechanistic Insights Through Imaging Mass Spectrometry.

PURPOSE: Chlorhexidine digluconate (CHG) is a first-line antiseptic agent typically applied to the skin as a topical solution prior to surgery due to its efficacy and safety profile. However, the physiochemical properties of CHG limits its cutaneous permeation, preventing it from reaching potentially pathogenic bacteria residing within deeper skin layers. Thus, the utility of a solid oscillating microneedle system, Dermapen®, and a CHG-hydroxyethylcellulose (HEC) gel were investigated to improve the intradermal delivery of CHG. METHODS: Permeation of CHG from the commercial product, Hibiscrub®, and HEC-CHG gels (containing 1% or 4% CHG w/w) was assessed in intact skin, or skin that had been pre-treated with microneedles of different array numbers, using an Franz diffusion cells and Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS). RESULTS: Gels containing 1% and 4% CHG resulted in significantly increased depth permeation of CHG compared to Hibiscrub® (4% w/v CHG) when applied to microneedle pre-treated skin, with the effect being more significant with the higher array number. ToF-SIMS analysis indicated that the depth of dermal penetration achieved was sufficient to reach the skin strata that typically harbours pathogenic bacteria, which is currently inaccessible by Hibiscrub®, and showed potential lateral diffusion within the viable epidermis. CONCLUSIONS: This study indicates that HEC-CHG gels applied to microneedle pre-treated skin may be a viable strategy to improve the permeation CHG into the skin. Such enhanced intradermal delivery may be of significant clinical utility for improved skin antisepsis in those at risk of a skin or soft tissue infection following surgical intervention.

Effect of nano-chitosan and nano-doxycycline gel on healing of induced oral ulcer in rat model: histological and immunohistochemical study.

OBJECTIVES: The aim of this study was to investigate the effect of nano-chitosan and nano-doxycycline gel on healing of oral ulcers. METHODS: In this study, 37 rats were used, four of which acted as normal controls (group 1), while the remaining 33 were distributed into three groups, each with 11 rats. Oral ulcers were chemically induced in the labial mucosa, after which (group 2), ulcer group received no treatment, (group 3) received nano-chitosan gel, and (group 4) received nano-doxycycline gel. They were scarified after 14 days and histologically examined as well as immunostaining for vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA). RESULTS: The best clinical and histologic healing results were shown in nano-chitosan group, followed by nano-doxycycline group, while the ulcer group showed incomplete healing. This was confirmed by immunostaining as area % of VEGF and number PCNA were the highest in nano-chitosan group followed by nano-doxycycline group, then ulcer group. CONCLUSION: Both nano-chitosan and nano-doxycycline gels improved the healing of chemically induced oral ulcers; however, nano-chitosan exhibited better healing outcomes. CLINICAL RELEVANCE: Nano-chitosan and nano-doxycycline gels are both viable and safe alternatives to current ulcer treatments.

Altered physical-chemical properties of home bleaching gels after an accelerated stability study and their effects on tooth enamel.

OBJECTIVES: To investigate the physical-chemical properties of home bleaching gels based on Carbamide Peroxide (CP) and Hydrogen Peroxide (HP) after accelerated stability (AS) and its effects on enamel. MATERIALS AND METHODS: A total of 360 bovine teeth blocks were divided (n = 12): Control, CP10%-Whiteness Perfect, CP10%-Pola Night, HP7.5%-Pola Day, and HP7.5%-White Class Calcium. Microhardness (KHN), roughness (Ra), color (ΔE and ΔE00), hardness, compressibility, elasticity, cohesiveness, adhesiveness, weight, pH, and calcium (Ca) quantification in enamel were analyzed without storage of the bleaching gels and after AS at 1 and 3 months. Data of Ca, KHN, and Ra were analyzed through mixed models for repeated measurements and the Tukey-Kramer test. Values of weight, hardness, compressibility, and elasticity were analyzed with two-way ANOVA and Tukey's test. ΔE/ΔE00 data, cohesiveness, and adhesiveness were analyzed with Kruskal-Wallis and Dunn tests (α = 0.05). RESULTS: Groups subject to AS had lower ΔE and ΔE00 compared to those without storage. Lower KHN and higher Ra values were found after bleaching treatment in all groups compared to controls. Higher amounts of Ca were found on the first day of evaluation in the gels subject to AS for 3 months, regardless of the bleaching agent used. CONCLUSIONS: Incorrectly stored bleaching gel accentuates adverse effects on enamel. Temperature and humidity interfere directly with the chemical stability of bleaching agents, reducing their properties. CLINICAL RELEVANCE: HP is an unstable oxidizing agent when stored at high temperatures. Therefore, pH becomes more acidic and potentiates the demineralizing effect on enamel.

Preparation, In Vitro and In Vivo Evaluation of Nanoemulsion In Situ Gel for Transnasal Delivery of Traditional Chinese Medicine Volatile Oil from Ligusticum sinense Oliv.cv. Chaxiong.

Ischemic stroke is a difficult-to-treat brain disease that may be attributed to a limited therapeutic time window and lack of effective clinical drugs. Nasal-brain administration is characterized by low systemic toxicity and is a direct and non-invasive brain targeting route. Preliminary studies have shown that the volatile oil of Chaxiong (VOC) has an obvious anti-ischemic stroke effect. In this work, we designed a nanoemulsion thermosensitive in situ gel (VOC-NE-ISG) loaded with volatile oil of Chaxiong for ischemia via intranasal delivery to rat brain treatment of cerebral ischemic stroke. The developed VOC-NE-ISG formulation has a suitable particle size of 21.02 ± 0.25 nm and a zeta potential of -20.4 ± 1.47 mV, with good gelling ability and prolonged release of the five components of VOC. The results of in vivo pharmacokinetic studies and brain targeting studies showed that intranasal administration of VOC-NE-ISG could significantly improve the bioavailability and had excellent brain-targeting efficacy of nasal-to-brain delivery. In addition, the results of pharmacodynamics experiments showed that both VOC-NE and VOC-NE-ISG could reduce the neurological deficit score of model rats, reducing the size of cerebral infarction, with a significant effect on improving ischemic stroke. Overall, VOC-NE-ISG may be a promising intranasal nanomedicine for the effective treatment of ischemic stroke.

Effect of highly concentrated bleaching gels on enamel microhardness and superficial morphology, and the recovery action of four remineralizing agents.

BACKGROUND: Dental bleaching is a common clinical practice. The aim of this study is to investigate the effect of 35% hydrogen peroxide (HP) bleaching gel on the morphology and microhardness of enamel, and to analyze the effect of four remineralizing agents. METHODS: One hundred blocks were prepared. The enamel surfaces were bleached with 35% HP in one session. The specimens were divided into four remineralization treatment groups (n = 25). G1: Tooth Mousse, G2: Remin-Pro, G3: Colgate Pro-Relif, G4: Mirafluor. The remineralizing protocol was applied 3 min per day for one week. Vickers microhardness (HV) measurements and SEM observations were performed at baseline, after bleaching, and after remineralizing treatment in all groups. Statistical analyses were performed using the paired t-test and ANOVA. RESULTS: After bleaching, SEM showed an increase of irregularities on the surface of the samples. Enamel microhardness decreased a mean of 47.7 HV, equivalent to a mean decrease of 18.3% (p < 0.05). After remineralization, the HV increased in all groups between 16 and 33% (p < 0.01), recovering the initial microhardness of enamel samples. SEM images revealed a higher quantity of superficial mineral deposits in groups 1 and 2 compared to the rest of the groups. CONCLUSIONS: The application of remineralizing products generates a significant increase in enamel microhardness. Tooth Mousse-treated samples showed a greater microhardness recovery, followed by Remin Pro. The superficial morphology of the samples reflects the results obtained in the HV tests.

Formulation development and evaluation of transdermal emulgel using Aloevera extract and natural penetration enhancers.

This study was to formulate Aloevera extract loaded emulsion (O/W) based gels, by using various concentrations of rose oil, olive oil and Lemon oil as natural penetration enhancers for transdermal effect to treat skin problems. By using RSM, Aloevera emulgels were formulated and then optimized. Stability studies, physico-chemical characteristics, spreadability, skin protection factor, thermal analysis, FTIR, antimicrobial activity, in vitro drug release study (at 37ºC with 100 rpm for 180 minute in release medium at pH 5.5) and in vivo skin evaluation tests were performed. The results were then statistically analyzed. Among all formulations, G12 has shown maximum 93.53% Aloevera release at higher concentration of Olive oil with decreased concentration of Rose oil and Lemon oil. Analysis of variance (ANOVA) was conducted to evaluate the results exhibited independent variables have remarkable effects on dependent variables. Contour plot is also drawn to express the response between independent and dependent variables. All formulations have followed Korsmeyer-Peppas kinetic model. In summary, the combination of penetration enhancers in Aloevera emulgel can be successfully utilized for treatment of mild-moderate acne vulgaris and other skin problems, as optimized emulgel has shown good permeability, prolonged residence time on skin surface and proved good anti-microbial activity.

Effects of a gel culture system made of polysaccharides (xanthan gum and locust bean gum) on in vitro bovine oocyte development and gene expression of the granulosa cells.

Xanthan gum (XG) and locust bean gum (LBG) are nontoxic polysaccharides that produce culture substrates. The present study examined the effect of XG-LBG gel on in vitro bovine oocyte growth and gene expression in granulosa cells. Oocytes and granulosa cell complexes (OGCs) were cultured in vitro on plastic culture plate (Plate) or XG-LBG gel for 16 days. OGCs formed a dome-like cavity surrounding the oocytes on plate but formed a spherical follicle structure on XG-LBG gel. The total granulosa cell numbers of the OGCs and their survival rate was greater for OGCs cultured on XG-LBG gel than for those cultured on plate. Oocytes grown on XG-LBG gels had higher lipid and mitochondrial content, as well as a larger diameter, than their plate counterparts. When oocytes grown in vitro were subjected to in vitro maturation and fertilization, the normal fertilization rate was significantly higher for oocytes developed on XG-LBG gel than that of oocytes cultured on the plate counterpart. RNAseq of the granulosa cells revealed that genes associated with focal adhesion, phosphatidylinositol 3'-kinase-Akt and Hippo signaling, and regulation of actin cytoskeleton were upregulated in granulosa cells of OGCs cultured on XG-LBG gel compared with those cultured on plate.

Anthocyanin complex niosome gel accelerates oral wound healing: In vitro and clinical studies.

An anthocyanin complex (AC), composed of extracts of purple waxy corn and blue butterfly pea petals, and AC niosomes, bilayered vesicles of non-ionic surfactants, were compared in in vitro and clinical studies. Cultured fibroblasts subjected to a scratch wound were monitored for cell viability, cell migration, nuclear morphology and protein expression. Scratched cells showed accelerated wound healing activity, returning to normal 24 h after treatment with AC niosomes (0.002 mg/mL). Western blots and immunocytochemistry indicated upregulation of type I, III and IV collagens, fibronectin and laminins in AC niosome-treated scratched cells. A randomized block placebo-controlled double-blind clinical trial in 60 volunteers (18-60 years old) with oral wounds indicated that AC niosome gel accelerated wound closure, reduced pain due to the oral wounds and improved participants' quality of life more than AC gel, triamcinolone gel and placebo gel. These data are consistent with enhanced delivery of AC to fibroblasts by use of niosomes. AC niosomes activated fibroblasts within wounded regions and accelerated wound healing, indicating that AC niosomes have therapeutic potential.

A Novel Carbon Dots/Thermo-Sensitive In Situ Gel for a Composite Ocular Drug Delivery System: Characterization, Ex-Vivo Imaging, and In Vivo Evaluation.

We developed a potential composite ocular drug delivery system for the topical administration of diclofenac sodium (DS). The novel carbon dot CDC-HP was synthesized by the pyrolysis of hyaluronic acid and carboxymethyl chitosan through a one-step hydrothermal method and then embedded in a thermosensitive in situ gel of poloxamer 407 and poloxamer 188 through swelling loading. The physicochemical characteristics of these carbon dots were investigated. The results of the in vitro release test showed that this composite ocular drug delivery system (DS-CDC-HP-Gel) exhibited sustained release for 12 h. The study of the ex vivo fluorescence distribution in ocular tissues showed that it could be used for bioimaging and tracing in ocular tissues and prolong precorneal retention. Elimination profiles in tears corresponded to the study of ex vivo fluorescence imaging. The area under the curve of DS in the aqueous humor in the DS-CDC-HP-Gel group was 3.45-fold that in the DS eye drops group, indicating a longer precorneal retention time. DS-CDC-HP with a positive charge and combined with a thermosensitive in situ gel might strengthen adherence to the corneal surface and prolong the ocular surface retention time to improve the bioavailability. This composite ocular delivery system possesses potential applications in ocular imaging and drug delivery.

Effects of Energy Gel Ingestion on Blood Glucose, Lactate, and Performance Measures During Prolonged Cycling.

ABSTRACT: Kozlowski, KF, Ferrentino-DePriest, A, and Cerny, F. Effects of energy gel ingestion on blood glucose, lactate, and performance measures during prolonged cycling. J Strength Cond Res 35(11): 3111-3119, 2021-Endurance athletes have long used carbohydrate supplementation during prolonged exercise (most recently with energy gels) to enhance performance. The purpose of this study was to determine the effect of carbohydrate energy gel ingestion schedules (e.g., manufacturer's recommendations vs. a more frequent ingestion schedule) during 2 hours of steady-state cycling exercise on (a) blood glucose, (b) blood lactate, and (c) performance of a subsequent 15-minute time trial (TT). Ten trained cyclists (5 men and 5 women, mean age = 28.4 ± 3.66 years; body mass = 68.9 ± 10.63 kg; and V̇o2max = 54.57 ± 9.45 mlO2·kg-1·min-1) performed 3 exercise trials in a randomized order. One gel was ingested 15 minutes before exercise during all trials. The 3 experimental trials included gel ingestion every 30 minutes (T1), every 45 minutes (T2) during exercise, and no gel ingested during exercise (T3). Subjects cycled at 70% of V̇o2max for 2 hours, followed by a 15-minute fixed gear TT. The blood glucose level at 60 minutes of exercise was higher during T1 (125.5 ± 30.96 mg·dl-1) and T2 (127.6 ± 14.82 mg·dl-1) compared with T3 (102.8 ± 15.85 mg·dl-1). Time trial distance was significantly greater for T1 (7.56 ± 0.77 km) and T2 (7.16 ± 0.92 km) than T3 (6.69 ± 0.74 km) (p = 0.003) with moderate to strong effect sizes between trials. There were no differences in blood lactate concentrations across trials. Ingestion of energy gels during prolonged cycling elevates blood glucose levels and enhances subsequent performance, whereas a more frequent ingestion elicits additional performance benefits.

Activity of Experimental Mouthwashes and Gels Containing DNA-RNA and Bioactive Molecules against the Oxidative Stress of Oral Soft Tissues: The Importance of Formulations. A Bioreactor-Based Reconstituted Human Oral Epithelium Model.

BACKGROUND: DNA-RNA compounds have shown promising protection against cell oxidative stress. This study aimed to assess the cytotoxicity, protective, or preventive effect of different experimental formulations on oral epithelia's oxidative stress in vitro. METHODS: Reconstituted human oral epithelia (RHOE) were grown air-lifted in a continuous-flow bioreactor. Mouthwashes and gels containing DNA-RNA compounds and other bioactive molecules were tested on a model of oxidative stress generated by hydrogen peroxide treatment. Epithelia viability was evaluated using a biochemical MTT-based assay and confocal microscopy; structural and ultrastructural morphology was evaluated by light microscopy and TEM. RESULTS: DNA-RNA showed non-cytotoxic activity and effectively protected against oxidative stress, but did not help in its prevention. Gel formulations did not express adequate activity compared to the mouthwashes. Excipients played a fundamental role in enhancing or even decreasing the bioactive molecules' effect. CONCLUSION: A mouthwash formulation with hydrolyzed DNA-RNA effectively protected against oxidative stress without additional enhancement by other bioactive molecules. Active compounds, such as hyaluronic acid, ß-Glucan, allantoin, bisabolol, ruscogenin, and essential oils, showed a protective effect against oxidative stress, which was not synergistic with the one of DNA-RNA. Incorporation of surfactant agents showed a reduced, yet significant, cytotoxic effect.