Development of Solid Lipid Nanoparticle-Loaded Polymeric Hydrogels Containing Antioxidant and Photoprotective Bioactive Compounds of Safflower (Carthamus tinctorius L.) for Improved Skin Delivery.

Safflower (Carthamus tinctorius L.) is a potent natural antioxidant because of active compounds such as quercetin (QU) and luteolin (LU). These components prevent damage to the skin caused by free radicals from UV rays. However, due to the poor solubility and transdermal permeation, the effectiveness of the compounds in showing their activity was limited. In this study, we develop solid lipid nanoparticle (SLN)-based hydrogel formulations to enhance the solubility and penetration of two bioactive compounds found in safflower petals extract (SPE). The hot emulsification-ultrasonication method was used to produce SLNs, and to obtain high antioxidant activity, 100% v/v ethanol was used in the extraction procedure. The results showed that this approach could encapsulate >80% of both QU and LU. Moreover, Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) spectra indicated that most of the QU and LU were trapped in a lipid matrix and dispersed homogeneously at the molecular level, increasing the solubility. Additionally, SLN-hydrogel composites are able to release two lipophilic bioactive compounds for 24 h, which also demonstrated increased skin retention and penetrability of the QU and LU up to 19-fold. In vitro blood biocompatibility showed that no hemolytic toxicity was observed below 500 µg/mL. Accordingly, the formulation was considered safe for use. Sun protective factor (SPF) test shows a value above 15, showing an excellent promising application as the photoprotective agent to prevent symptoms associated with photoinduced skin aging.

Molecular Docking Study of the C-10 Massoia Lactone Compound as an Antimicrobial and Antibiofilm Agent against Candida tropicalis.

Antimicrobial resistance is now considered a global health problem because it reduces the effectiveness of antimicrobial drugs. According to the World Health Organization (WHO), the highest mortality rate is associated with infections caused by multidrug-resistant microorganisms, with approximately 700,000 deaths worldwide each year. The aim of this study was to determine the potential of C-10 massoia lactone to inhibit the growth of fungi and C. tropicalis biofilm, and molecular docking studies were performed to determine the nature of the inhibition. The study was conducted using the microdilution method for antifungal and antibiofilm testing and designed with a molecular docking approach. Furthermore, an analysis using the scanning electron microscope (SEM) was performed to evaluate the mechanism of effect. The results obtained showed that C-10 massoia lactone can inhibit the growth of fungi by 84.21% w/v. Meanwhile, the growth of C. tropicalis biofilm in the intermediate phase was 80.23% w/v and in the mature phase was 74.23% w/v. SEM results showed that C-10 massoia lactone damaged the EPS matrix of C. tropicalis so that hyphal formation was hindered due to damage to fungal cells, resulting in a decrease in attachment, density, and lysis of C. tropicalis fungal cells. Based on molecular docking tests, C-10 massoia lactone was able to inhibit biofilm formation without affecting microbial growth, while docking C-10 massoia lactone showed a significant binding and has the potential as an antifungal agent. In conclusion, the C-10 massoia lactone compound has the potential as an antibiofilm against C. tropicalis, so it can become a new antibiofilm agent.

Design and characterization of propolis extract loaded self-nano emulsifying drug delivery system as immunostimulant.

This current study aims to optimize, characterize, and observe the stability of the self-nano emulsifying drug delivery system (SNEDDS) of propolis extract (PE) for improving the immune response. Optimization of the selected composition of SNEDDS was conducted using a D-optimal mixture design. SNEDDS was prepared by loading 150 mg/mL of PE in oil, surfactant, and cosurfactant phases. The thermodynamic stability test was carried out with phase separation parameters followed by the robustness to dilution and accelerated stability test. The immunostimulant activity was examined in vitro and in vivo by determining the phagocytic activity, cell proliferation, production of nitrite oxide levels of RAW 264.7 cells, phagocytic activity of macrophages, and the number of leukocytes, neutrophils, and lymphocytes. The formula optimization showed that the formula containing Capryol-90, Cremophor RH40, and PEG 400 at a ratio of 30: 34: 36 was optimum. The verification response of the optimum formula with drug loading showed that the transmittance, droplet size, and zeta potential were 96.90 ± 0.00%, 28.7 ± 1.20 nm, and -56.5 ± 2.05 mV, respectively. The thermodynamic stability test and robustness to dilution did not find any separation phase. The accelerated stability test results were classified as stable. The in vitro and in vivo immunostimulant activity test showed that PE-loaded SNEDDS exhibited a higher immunostimulant effect than PE. In conclusion, the optimum and stable composition of PE loaded SNEDDS was found with a simple and accurate method using the D-Optimal mixture design and demonstrated an immunostimulant activity.

Turn-off/turn-on biosensing of tetracycline and ciprofloxacin antibiotics using fluorescent iron oxide quantum dots.

A fluorescence probe based on iron oxide quantum dots (IO-QDs) was synthesized using the hydrothermal method for the determination of tetracycline (TCy) and ciprofloxacin (CPx) in aqueous solution. The IO-QDs were characterized using high-resolution transmission electron microscopy (HR-TEM), powder X-ray diffraction (P-XRD), vibrating sample magnetometry (VSM), and Fourier-transform infrared spectroscopy (FTIR). The as-prepared IO-QDs are fluorescent, stable, and with a fluorescence quantum yield (QY) of 9.8 ± 0.12%. The fluorescence of IO-QDs was observed to be quenched and enhanced in the presence of TCy and CPx, respectively. The fluorescence intensity ratio shows linearity at concentrations from 1-100 µM and 5-100 µM for TCy and CPx, respectively; the detection limit for TCy and CPx was estimated to be 0.71 µM and 1.56 µM, respectively. The proposed method was also successfully utilized in the spiked samples of drinking water and honey with good recoveries. The method offered convenience, rapid detection, high sensitivity, selectivity, and cost-efficient alternative options for the determination of TCy and CPx in real samples.

Polyvinylpyrrolidone-passivated fluorescent iron oxide quantum dots for turn-off detection of tetracycline in biological fluids.

Tetracycline is an antibiotic that has been prescribed for COVID-19 treatment, raising concerns about antibiotic resistance after long-term use. This study reported fluorescent polyvinylpyrrolidone-passivated iron oxide quantum dots (IO QDs) for detecting tetracycline in biological fluids for the first time. The as-prepared IO QDs have an average size of 2.84 nm and exist a good stability under different conditions. The IO QDs' tetracycline detection performance could be attributed to a combination of static quenching and inner filter effect. The IO QDs displayed high sensitivity and selectivity toward tetracycline and achieved a good linear relationship with the corresponding detection limit being 91.6 nM.

Tracking of the Antibiofilm Activities of Lakum Leaf Extract (Causonis trifolia Linn.) Against Staphylococcus aureus.

<b>Background and Objective:</b> Biofilms as a bacterial defense are relatively more difficult to eradicate with antibiotics, thus pathogenic bacteria in their biofilm form can cause serious problems for human health. Lakum <i>(Causonis trifolia</i> L.) is an herbaceous plant with many biological activities, one of which is an antimicrobial compound containing flavonoids, squalene, nimbidin, saponins, anthocyanins, tannins, myricetin, others. This study aimed to determine the antibiofilm activity of Lakum leaf extract against<i> Staphylococcus aureus </i>bacteria and the active compounds that play a role in inhibiting monomicrobial biofilms. <b>Materials and Methods:</b> This research method was carried out with an <i>in vitro</i> experimental study design using observations of phytochemical screening test results and the effectiveness of Lakum leaf antibiofilm on<i> Staphylococcus aureus</i> through microplate reader readings that measure optical density values. <b>Results:</b> This study showed that Lakum leaves contain alkaloids, flavonoids, phenolics, polyphenols, tannins and saponins. In addition, Lakum leaves gave biofilm inhibitory activity in the middle and maturation phase with the highest concentration in 1% extract of 76.95±0.0007 and 72.85± 0.0003%, respectively. Meanwhile, the lowest concentration was 0.125% extract of 65.65±0.0001% in the middle phase and 59.71±0.0003% in the maturation phase. <b>Conclusion:</b> That Lakum leaves have biofilm inhibitory activity on <i>Staphylococcus aureus</i> with flavonoid compounds, tannins and polyphenols that work as active substances in inhibiting the biofilm formation.

Solid lipid nanoparticles cyclodextrin-decorated incorporated into gellan gum-based dry floating in situ delivery systems for controlled release of bioactive compounds of safflower (Carthamus tinctorius. L): A proof of concept study in biorelevant media.

Safflower (Carthamus tinctorius L.) has been explored as a source of natural antioxidant. However, quercetin 7-O-beta-D-glucopyranoside and luteolin 7-O-beta-D-glucopyranoside, as its bioactive compounds, possessed poor aqueous solubility, limiting its efficacy. Here, we developed solid lipid nanoparticles (SLNs) decorated with hydroxypropyl beta-cyclodextrin (HPßCD) incorporated into dry floating gel in situ systems to control the release of both compounds. Using Geleol® as a lipid matrix, SLNs were <200 nm in size with >80 % of encapsulation efficiency. Importantly, following the decoration using HPßCD, the stability of SLNs in gastric environment was significantly improved. Furthermore, the solubility of both compounds was also enhanced. The incorporation of SLNs into gellan gum-based floating gel in situ provided desired flow and floating properties, with <30 s gelation time. The floating gel in situ system could control the release of bioactive compounds in FaSSGF (Fasted-State Simulated Gastric Fluid). Furthermore, to assess the effect of food intake on release behavior, we found that the formulation could show a sustained release pattern in FeSSGF (Fed-State Simulated Gastric Fluid) for 24 h after being released in FaSGGF for 2 h. This indicated that this combination approach could be a promising oral delivery for bioactive compounds in safflower.

Dual delivery systems combining nanocrystals and dissolving microneedles for improved local vaginal delivery of fluconazole.

Fluconazole (FLZ) has been widely used in the treatment of infection caused by Candida albicans, including the treatment of vulvovaginal candidiasis (VVC). However, when delivered orally, FLZ faces numerous limitations due to its poor solubility and undergoes the symptoms of first-pass metabolism. In this study, we developed the combinatorial approach of nanocrystals (NCs) and dissolving microneedles (DMNs) for effective local vaginal delivery of FLZ. The formulation containing 1.0% w/v PVA as stabilizer with 12 h of milling time process was found to be an optimal combination to fabricate FLZ as NCs (FLZ-NCs) with optimum size particle and PDI value (less than 0.25). Furthermore, the in vitro release study also showed a superior percentage of FLZ release up to 89.51 ± 7.52%. In combination with the DMNs, the FLZ recovery was 96.45 ± 2.38% with the insertion percentage in average of 76.14 ± 2.28% and height decreased percentage was only 7.53 ± 0.56%. Moreover, the ex vivo investigation and anti-candidiasis activity of DMNs-FLZ-NCs in vaginal model showed better results compared to other conventional preparations, such as film patch and hydrogel containing FLZ.

Compatibility of acetaminophen with central nervous system medications during simulated Y-site injection.

BACKGROUND: The critical care patient commonly receives a lot of medications including acetaminophen and central nervous system (CNS) agents. However, research on compatibility between acetaminophen and CNS medication is still limited. METHODS: Physical compatibility was evaluated using Y-site simulation by mixing one CNS medication with 10 mg mL-1 of acetaminophen solution under aseptic conditions with a 1 : 1 ratio. The Y-site simulation mixture was subsequently kept in a clean glass tube for incompatibility investigation during 24 hours. The aliquot solutions were visually inspected with bare eyes then additionally with a Tyndall light beam, microscope, and pH at 0, 1, 4, and 24 hours. Medications were considered compatible if there was no visual change (color/gas or turbidity), and no significant particles or precipitates, which referred to United States Pharmacopeia 788 (USP 788), and pH changes less than 0.5 units. RESULTS: During 24 hours, intravenous acetaminophen was physically compatible with haloperidol, ketamine, midazolam, pethidine, rocuronium and tramadol. Meanwhile, phenytoin, and propofol showed incompatibility with acetaminophen right away. Within four hours, five medications (dexketoprofen, fentanyl, ketorolac, diazepam and phenobarbital) showed incompatibility. Two medications (atropine sulfate and metamizole) were also found to be incompatible with acetaminophen under observation for 24 hours. CONCLUSIONS: Nine of 15 common CNS medications in critical care tested with acetaminophen were physically incompatible for 24 hours.

Effects of Pegagan (Centella asiatica L.) Ethanolic Extract SNEDDS (Self-nanoemulsifying Drug Delivery Systems) on the Development of Zebrafish (Danio rerio) Embryos.

INTRODUCTION: Pegagan is a traditional medicinal plant with three major bioactive properties, triterpenoid, steroids, and saponin. It has the properties of antioxidant, antistress, and wound healing. Pegagan extract is prepared in self-nanoemulsifying drug delivery systems (SNEDDS) to overcome the problem of low water-solubility level. OBJECTIVES: This study aimed to observe the effect of pegagan ethanolic extract SNEDDS on the development of zebrafish embryos. MATERIALS AND METHODS: This study used 12 sets of zebrafish embryos presented in five sets of extract SNEDDS with different concentrations, that is, 20, 10, 5, 2.5, and 1.25 µg, five sets of SNEDDS without extract with different concentrations, that is, 20, 10, 5, 2.5, and 1.25 µg, a set of positive control (3.4-DCA 4 mg/L) with one control set (diluted with water), and a negative control (SNEDDS without extract). The procedure was conducted for 96 h with observations every 24 h. The parameters observed were embryonic coagulation, formation of somites, detachment of tail bud from the yolk, and abnormality of embryo. RESULTS: The results showed that in 96 h the 20ppm concentration caused 100% mortality. Embryo abnormality appeared as coagulation of embryo, somite malformation, and abnormal tail. DISCUSSION: There is a correlation between the concentration of SNEDDS and the incidence of embryo coagulation. The malformation in the group of pegagan extract SNEDDS is characterized by cardiac edema, somite malformation, and abnormal tail. CONCLUSION: Pegagan ethanolic extract SNEDDS of 20ppm can inhibit the development of zebrafish embryos.