Effects of Salts and Other Contaminants on Ciprofloxacin Removal Efficiency of Green Synthesized Copper Nanoparticles.

Ciprofloxacin (CIP), a broad-spectrum fluoroquinolone antibiotic, is commonly used in aquaculture to prevent and treat bacterial infections in aquatic animals. For this reason, aquatic environments contain CIP and its derivatives, which lead to the development of drug-resistant bacteria. In the present study, copper nanoparticles were prepared using Garcinia mangostana extract (GME-CuNPs) as a reducing agent and evaluated for their CIP removal efficiency (CRE). The results demonstrate that within 20 min, GME-CuNPs at 25 mM possess a CRE of 92.02 ± 0.09% from CIP-containing aqueous media with pH 6-7. The CRE is influenced by both monovalent and divalent salts. A high salt concentration significantly reduces the CRE. Contaminants in fish wastewater can reduce the CRE, but phenolics, flavonoids, tannins, and ammonia do not affect the CRE. Our results reveal that the CRE is controlled by electrostatic attraction between the negatively charged GME-CuNPs and the cationic species of CIP. The CRE is reduced by wastewater with a pH higher than 8.0, in which the CIP molecules have a negative charge, resulting in a repulsive force due to the negative charge of GME-CuNPs. In fish wastewater with a pH lower than 7.0, GME-CuNPs show the potential to achieve a CRE above 80%. Therefore, pH adjustment to a range of 6-7 in fish wastewater before treatment is deemed imperative. It is concluded that the newly developed GME-CuNPs possess excellent activity in CIP elimination from actual fish wastewater samples. Our findings suggest that GME-CuNPs can be a promising tool to effectively eliminate antibiotics from the environment.

Modification of Polyethylene Glycol-Hydroxypropyl Methacrylate Polymeric Micelles Loaded with Curcumin for Cellular Internalization and Cytotoxicity to Wilms Tumor 1-Expressing Myeloblastic Leukemia K562 Cells.

Curcumin loaded in micelles of block copolymers of ω-methoxypoly(ethylene glycol) and N-(2-hydroxypropyl) methacrylamide modified with aliphatic dilactate (CD) or aromatic benzoyl group (CN) were previously reported to inhibit human ovarian carcinoma (OVCAR-3), human colorectal adenocarcinoma (Caco-2), and human lymphoblastic leukemia (Molt-4) cells. Myeloblastic leukemia cells (K562) are prone to drug resistance and differ in both cancer genotype and phenotype from the three mentioned cancer cells. In the present study, CD and CN micelles were prepared and their effects on K562 and normal cells were explored. The obtained CD and CN showed a narrow size distribution with diameters of 63 ± 3 and 50 ± 1 nm, respectively. The curcumin entrapment efficiency of CD and CN was similarly high, above 80% (84 ± 8% and 91 ± 3%). Both CD and CN showed suppression on WT1-expressing K562 and high cell-cycle arrest at the G2/M phase. However, CD showed significantly higher cytotoxicity to K562, with faster cellular uptake and internalization than CN. In addition, CD showed better compatibility with normal red blood cells and peripheral blood mononuclear cells than CN. The promising CD will be further investigated in rodents and possibly in clinical studies for leukemia treatment.

Comparative effectiveness and mortality of colistin monotherapy versus colistin-fosfomycin combination therapy for the treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections: A propensity score analysis.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) infections pose a significant threat to global health due to limited treatment options and high mortality rates. Colistin-based regimens have emerged as a primary treatment approach, but the effectiveness and mortality outcomes of colistin monotherapy versus colistin-fosfomycin combination therapy remain uncertain. This study aims to compare the effectiveness and mortality of colistin monotherapy and colistin-fosfomycin combination therapy for CRE infections. Notably, our study is the first to undertake a comprehensive examination of the effectiveness and mortality outcomes between colistin monotherapy and colistin-fosfomycin combination therapy in the context of CRE infections. METHODS: A retrospective cohort study was conducted using data from patients diagnosed with carbapenem-resistant Enterobacteriaceae (CRE) infections at Nakornping Hospital during 2015 to 2022. Inverse probability weighting (IPW) was employed to create balanced cohorts of patients receiving either colistin monotherapy or colistin-fosfomycin combination therapy. The primary outcome measure was treatment effectiveness, assessed by 30-day mortality. Secondary outcome measures included clinical response, mortality at the end of treatment, and microbiologic response. Univariate and multivariate logistic regression analysis were employed after applying propensity score weighting using inverse probability of weighting (IPW). RESULTS: A total of 220 patients were included in the analysis, with 67 receiving colistin monotherapy and 153 receiving colistin-fosfomycin combination therapy. Propensity score weighting using IPW balanced the baseline characteristics between the two groups. The effectiveness of treatment, as measured by 30-day mortality, was not significantly different between the colistin monotherapy group and the colistin-fosfomycin combination therapy group (adjusted odds ratio [aOR] = 1.51, 95% confidence interval [CI]: 0.60-3.78, p = 0.383). Similarly, no significant difference was observed in the mortality at the end of treatment between the two groups (aOR = 1.26, 95% CI: 0.55-2.90, p = 0.576). The clinical response (aOR = 1.48, 95% CI: 0.61-3.59, p = 0.383) and microbiologic response (aOR = 0.66, 95% CI: 0.18-2.38, p = 0.527) were similar between the colistin monotherapy and colistin-fosfomycin combination therapy groups. CONCLUSION: The propensity score analysis among 220 matched patients showed comparable treatment effectiveness and mortality between colistin monotherapy and colistin-fosfomycin combination therapy for CRE infections. These results suggest that colistin monotherapy may be as effective as combination therapy. More prospective randomized controlled trials are needed to confirm these findings and establish optimal CRE treatment strategies.

Anticancer activity of Curcuma aeroginosa essential oil and its nano-formulations: cytotoxicity, apoptosis and cell migration effects.

BACKGROUND AND AIMS: Curcuma aeruginosa, commonly known as "kha-min-dam" in Thai, holds significance in Asian traditional medicine due to its potential in treating various diseases, having properties such as anti-HIV, hepatoprotective, antimicrobial and anti-androgenic activities. This study explores the anticancer activity of C. aeruginosa essential oil (CAEO) and its nano-formulations. METHODS: CAEO obtained from hydrodistillation of C. aeruginosa fresh rhizomes was examined by gas chromatography mass spectroscopy. Cytotoxicity of CAEO was determined in leukaemic K562 and breast cancer MCF-7 cell lines using an MTT assay. Cell cycle analysis and cell apoptosis were determined by flow cytometry. Cell migration was studied through a wound-healing assay. RESULTS: Benzofuran (33.20%) emerged as the major compound of CAEO, followed by Germacrene B (19.12%) and Germacrone (13.60%). Two types of CAEO loaded nano-formulations, nanoemulsion (NE) and microemulsion (ME) were developed. The average droplet sizes of NE and ME were 13.8 ± 0.2 and 21.2 ± 0.2 nm, respectively. In a comparison with other essential oils from the fresh rhizomes of potential plants from the same family (Curcuma longa, Curcuma mangga and Zingiber officinale) on anticancer activity against K562 and MCF-7 cell lines, CAEO exhibited the highest cytotoxicity with IC50 of 13.43 ± 1.09 and 20.18 ± 1.20 µg/mL, respectively. Flow cytometry analysis revealed that CAEO significantly increased cell death, evidenced from the sub-G1 populations in the cell cycle assay and triggered apoptosis. Additionally, CAEO effectively inhibited cell migration in MCF-7 cells after incubation for 12 and 24 h. The developed NE and ME formulations significantly enhanced the cytotoxicity of CAEO against K562 cells with an IC50 of 45.30 ± 1.49 and 41.98 ± 0.96 µg/mL, respectively. CONCLUSION: This study's finding suggest that both nano-formulations, NE and ME, effectively facilitated the delivery of CAEO into cancer cells.

Clerodendrum chinense Stem Extract and Nanoparticles: Effects on Proliferation, Colony Formation, Apoptosis Induction, Cell Cycle Arrest, and Mitochondrial Membrane Potential in Human Breast Adenocarcinoma Breast Cancer Cells.

Breast cancer stands out as the most widespread form of cancer globally. In this study, the anticancer activities of Clerodendrum chinense (C. chinense) stem ethanolic extract were investigated. High-performance liquid chromatography (HPLC) analysis identified verbascoside and isoverbascoside as the major bioactive compounds in the C. chinense stem extract. Successfully developed nanoparticles exhibited favorable hydrodynamic diameter, polydispersity index, and surface charge, thus ensuring stability after four months of storage. The total phenolic content and total flavonoid contents in the nanoparticles were reported as 88.62% and 95.26%, respectively. The C. chinense stem extract demonstrated a dose-dependent inhibitory effect on MCF-7, HeLa, A549, and SKOV-3 cancer cell lines, with IC50 values of 109.2, 155.6, 206.9, and 423 µg/mL, respectively. C. chinense extract and NPs exhibited dose-dependent cytotoxicity and the highest selectivity index values against MCF-7 cells. A dose-dependent reduction in the colony formation of MCF-7 cells was observed following treatment with the extract and nanoparticles. The extract induced cytotoxicity in MCF-7 cells through apoptosis and necrosis. C. chinense stem extract and nanoparticles decreased mitochondrial membrane potential (MMP) and induced G0/G1 phase arrest in MCF-7 cells. In conclusion, use of C. chinense stem extract and nanoparticles may serve as a potential therapeutic approach for breast cancer, thus warranting further exploration.

Fabrication and Optimization of Electrospun Shellac Fibers Loaded with Senna alata Leaf Extract.

Single-fluid electrospinning creates nanofibers from molten polymer solutions with active ingredients. This study utilized a combination of a fractional factorial design and a Box-Behnken design to examine crucial factors among a multitude of parameters and to optimize the electrospinning conditions that impact fiber mats' morphology and the entrapment efficiency of Senna alata leaf extract. The findings indicated that the shellac content had the greatest impact on both fiber diameter and bead formation. The optimum electrospinning conditions were identified as a voltage of 24 kV, a solution feed rate of 0.8 mL/h, and a shellac-extract ratio of 38.5:3.8. These conditions produced nanosized fibers with a diameter of 306 nm, a low bead-to-fiber ratio of 0.29, and an extract entrapment efficiency of 96% within the fibers. The biphasic profile of the optimized nanofibers was confirmed with an in vitro release study. This profile consisted of an initial burst release of 88% within the first hour, which was succeeded by a sustained release pattern surpassing 90% for the next 12 h, as predicted with zero-order release kinetics. The optimized nanofibers demonstrated antimicrobial efficacy against diverse pathogens, suggesting promising applications in wound dressings and protective textiles.

Utilizing liposomal encapsulation approach to address nephrotoxic challenges of colistimethate sodium through a preclinical study.

The use of Colistin, a last-resort antimicrobial drug, carries the risk of acute kidney injury. The objective of the study was to assess the effectiveness of colistin-encapsulated liposomes (CL) in reducing nephrotoxicity. Additionally, a liposomal preparation of colistimethate sodium was formulated using the reverse phase evaporation method with a 3:1 ratio of phospholipids to cholesterol. The liposomal properties were evaluated using scanning electron microscopy, photon correlation spectroscopy, and release kinetic assay. The killing kinetics of the formulations on embryonic kidney cells were assessed using in vitro MTT reduction assay. The nephrotoxicity of CL and colistimethate sodium solution (CS) was evaluated in vivo by administering a dose of 20 mg/kg to rats every 12 h for 3 days, with a negative control group receiving a 0.9% saline solution (NSS). The study results revealed that monodisperses of CL showed a smooth surface and distinct boundaries, with an average size of 151.50 ± 0.46 nm and a narrow size distribution of 0.25 ± 0.01. The liposomal particles showed high entrapment efficiency of 96.45% ± 0.41%, with a ζ-potential of -60.80 ± 1.01 mV and a release rate of 50% of colistimethate sodium within the first 480 min. The CL induced nephrocytotoxicity in a concentration- and time-dependent manner. However, CS had notably lower IC50 values compared to its liposome preparations at 48 and 72 h (p < 0.05). In vivo study results show that serum levels of symmetric dimethylarginine (SDMA) and total white blood cell count (WBC) were significantly lower in the CL group (SDMA = 8.33 ± 1.70 µg/dL; WBC = 7.29 ± 0.99 log10 cells/mL) compared to the CS group (SDMA = 15.00 ± 1.63 µg/dL; WBC = 9.73 ± 0.51 log10 cells/mL). Our study findings enhance the understanding of the safety profile of CL and its potential to improve patient outcomes through the use of liposomal colistin medication. Additional clinical studies are necessary to establish the optimal safety regiment in humans.

Solubility and Physical Stability Enhancement of Loratadine by Preparation of Co-Amorphous Solid Dispersion with Chlorpheniramine and Polyvinylpyrrolidone.

Loratadine (LRD), a non-sedating and slow-acting antihistamine, is often given in combination with short-onset chlorpheniramine maleate (CPM) to increase efficacy. However, LRD has poor water solubility resulting in low bioavailability. The aim of this study was to improve LRD solubility by preparing co-amorphous LRD-CPM. However, the obtained co-amorphous LRD-CPM recrystallized rapidly, and the solubility of LRD returned to a poor state again. Therefore, co-amorphous LRD-CPM solid dispersions using polyvinylpyrrolidone (PVP) as a carrier were prepared. The obtained solid dispersions were characterized using X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR). The solubility, dissolution, and mechanism of drug release from the LRD-CPM/PVP co-amorphous solid dispersions were studied and compared with those of intact LRD, LRD/PVP solid dispersions, and co-amorphous LRD-CPM mixtures. The results from XRPD and DSC confirmed the amorphous form of LRD in the co-amorphous solid dispersions. The FTIR results indicated that there was no intermolecular interaction between LRD, CPM, and PVP. In conclusion, the obtained LRD-CPM/PVP co-amorphous solid dispersions can successfully increase the water solubility and dissolution of LRD and extend the amorphous state of LRD without recrystallization.

Effects of Encapsulation of Caesalpinia sappan L. with Cyclodextrins for Bovine Mastitis.

The main components of Caesalpinia sappan L. (CS) are brazilin and brazilein, which show high potential in pharmacologic applications. However, these have been drastically limited by the poor water solubility and stability. The present study investigates the formation of inclusion complexes F1, F2, and F3 between CS and ß-cyclodextrin (ßCD), hydroxypropyl-ß-cyclodextrin (HPßCD), and methyl-ß-cyclodextrin (MßCD), respectively. These complexes were characterized by Fourier transform infrared spectroscopy (FT-IR). The results showed that the highest encapsulation efficiency and loading capacity of CS extract were 44.24% and 9.67%, respectively. The solubility and stability of CS extract were significantly increased through complexation in phase solubility and stability studies. The complexes F1-F3 showed mainly significant antibacterial activities on gram-positive bacteria pathogens causing mastitis. Moreover, the expression levels of COX-2 and iNOS were significantly decreased in LPS-induced inflammatory cells at concentrations of 50 and 100 µg/mL. In addition, treatment of complex F3 (CS/MßCD) in bovine endothelial cells remarkably increased the chemokine gene expression of CXCL3 and CXCL8, which were responsible for immune cell recruitment (9.92 to 11.17 and 8.23 to 9.51-fold relative to that of the LPS-treated group, respectively). This study provides a complete characterization of inclusion complexes between CS extract and ßCD, HPßCD, and MßCD for the first time, highlighting the impact of complex formation on the pharmacologic activities of bovine mastitis.

Effects of plant-based copper nanoparticles on the elimination of ciprofloxacin.

Ciprofloxacin (CIP) is frequently detected in the environment and causes the emergence of drug-resistant bacteria. High levels of CIP in the environment are also harmful to humans and animals. Therefore, effective elimination of CIP is required. In this study, plant-based copper nanoparticles (CuNPs) have been fabricated for the purpose of eliminating CIP. Aqueous extracts of 6 plants were compared for their phytochemicals and reducing activity. Among all the extracts, Garcinia mangostana extract (GM) was the most potent with the highest total phenolic compounds, flavonoids, tannins, terpenoids, and reducing activity. CuNPs synthesized using GM (GM-CuNPs) were characterized using UV-VIS spectroscopy and dynamic light scattering. The results showed that the maximum absorption of GM-CuNPs was at 340 nm. The average size of GM-CuNPs is in the nanoscale range of 159.2 ± 61 nm, with a narrow size distribution and a negative zeta potential of - 4.13 ± 6.97 mV. The stability of GM-CuNPs is not solely due to their zeta potential but also phytochemicals in the extract. GM-CuNPs at 25 mM showed the highest efficiency of 95% in removing CIP from aqueous medium pH 6-7 at 25-35°C within 20 min. The results indicated that the electrostatic attraction between the negative charge of GM-CuNPs and the positive charge of CIP controlled the drug adsorption on the nanoparticles. In conclusion, the developed GM-CuNPs have excellent CIP removal efficiency. These synthesized GM-CuNPs are expected to be environmentally friendly for the removal of antibiotics and other drugs.

Efficacy of Andrographis paniculata spray in acute pharyngitis: A randomized controlled trial.

Acute viral pharyngitis is a self-limited disease but the symptoms, a sore throat in particular, can affect one's quality of life. Medicine for symptom relief is the main treatment. Recently, many studies have shown that Andrographis paniculata was efficacious in treating many diseases, including upper respiratory infections. However, adverse reactions to systemic intake are a concern. Therefore, A. paniculata spray is intended to reduce systemic adverse reactions and provide patients with more comfort as its local use. This randomized, double-blind study enrolled 60 adult patients with acute viral pharyngitis. All patients were asked to score the severity of symptoms including a sore throat, difficulty swallowing, and coughing using an 11-point numeric rating scale from 0 to 10. A physical examination was performed to score the severity of erythematous and swollen mucosa using a 0-3 score (0 = no, 1 = mild, 2 = moderate, and 3 = severe). The patients were randomized to receive treatment with either an A. paniculata spray or a positive control chamomile spray. Results revealed a significant reduction in the severity of all signs and symptoms in both groups (p < 0.05). The duration of treatment response in the A. paniculata spray group was 1.9 ± 0.7 days compared to 2.5 ± 1.2 days in the chamomile spray group (p = 0.049). No adverse events were noted in either group. A. paniculata spray is safe and highly efficacious in treating acute viral pharyngitis and can reduce symptoms more rapidly than a positive control spray.

Computational Insight of Phase Transformation and Drug Release Behaviour of Doxycycline-Loaded Ibuprofen-Based In-Situ Forming Gel.

This research investigates the gel formation behaviour and drug-controlling performance of doxycycline-loaded ibuprofen-based in-situ forming gels (DH-loaded IBU-based ISGs) for potential applications in periodontal treatment. The investigation begins by exploring the physical properties and gel formation behaviour of the ISGs, with a particular focus on determining their sustained release capabilities. To gain a deeper understanding of the molecular interactions and dynamics within the ISGs, molecular dynamic (MD) simulations are employed. The effects of adding IBU and DH on reducing surface tension and water tolerance properties, thus affecting molecular properties. The phase transformation phenomenon is observed around the interface, where droplets of ISGs move out to the water phase, leading to the precipitation of IBU around the interface. The optimization of drug release profiles ensures sustained local drug release over seven days, with a burst release observed on the first day. Interestingly, different organic solvents show varying abilities to control DH release, with dimethyl sulfoxide (DMSO) demonstrating superior control compared to N-Methyl-2-pyrrolidone (NMP). MD simulations using AMBER20 software provide valuable insights into the movement of individual molecules, as evidenced by root-mean-square deviation (RMSD) values. The addition of IBU to the system results in the retardation of IBU molecule movement, particularly evident in the DMSO series, with the diffusion constant value of DH reducing from 1.2452 to 0.3372 and in the NMP series from 0.3703 to 0.2245 after adding IBU. The RMSD values indicate a reduction in molecule fluctuation of DH, especially in the DMSO system, where it decreases from over 140 to 40 Å. Moreover, their radius of gyration is influenced by IBU, with the DMSO system showing lower values, suggesting an increase in molecular compactness. Notably, the DH-IBU configuration exhibits stable pairing through H-bonding, with a higher amount of H-bonding observed in the DMSO system, which is correlated with the drug retardation efficacy. These significant findings pave the way for the development of phase transformation mechanistic studies and offer new avenues for future design and optimization formulation in the ISG drug delivery systems field.

Comparative Safety and Effectiveness of Heterologous CoronaVac-ChAdOx1 versus Homologous CoronaVac Vaccination in a Real-World Setting: A Retrospective Cohort Study.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has outpaced vaccine availability and delivery from vaccine manufacturers, and thus, a scarcity of vaccines happened to many countries around the world. In Thailand, the mixing of different types of vaccines was approved and clinically implemented partially due to concerns about the availability and efficacy of one vaccine. Objective: This study aimed to investigate the effectiveness and safety of heterologous CoronaVac-ChAdOx1 nCoV-19 vaccines compared with the usual regimen of homologous CoronaVac-CoronaVac. A retrospective cohort study was conducted by dividing patients into the CoronaVac-CoronaVac group and the CoronaVac-ChAdOx1 group. Results: A total of 875 patients received vaccinations at Srisangwan Hospital between April to October 2021 and were included for analysis. The patients in both homologous and heterologous groups had low rates of COVID-19 infection. In addition, the hospitalization rates in the 40 days after the second vaccination were low in both regimens. Minimal adverse events (AE) were reported in both groups, including local AE (e.g., discomfort at the injection site, rash, soreness, swelling, and redness) and systemic AE (e.g., fever, headache, weariness, nausea, vomiting, diarrhoea, and myalgia). Moreover, several factors were associated with lower adverse events following immunization (AEFIs), including age ≥ 50 years, male, and body weight ≥ 50 kg. In contrast, thyroid disease, diabetes mellitus, allergic rhinitis, and psychiatric disorders were independent risk factors associated with an increase in AEFIs. Conclusions: The heterologous CoronaVac-ChAdOx1 and homologous CoronaVac-CoronaVac regimens were promising vaccination strategies for the prevention of SARS-CoV-2 infection. However, the heterologous CoronaVac-ChAdOx1 potentially caused fewer AEFIs compared with the homologous CoronaVac-CoronaVac regimen.

Biosynthesis of copper oxide nanoparticles using Caesalpinia sappan extract: In vitro evaluation of antifungal and antibiofilm activities against Candida albicans.

Synthesis of nanoparticles using natural organic substances has attracted more attention due to avoiding inorganic toxicity. This work aimed to synthesize copper oxide nanoparticles (CuONPs) using Caesalpinia sappan heartwood extract as a reducing agent. The effects of pH of synthesis reaction were investigated. The obtained CuONPs were characterized using UV-visible spectroscopy, Fourier transform infrared spectroscopy, scanning electron microscopy, and energy dispersive X-ray spectroscopy. Their particle size, size distribution, and zeta potential were determined using photon correlation spectrophotometry. Candida albicans is a major cause of chronic fungal infections due to its biofilms leading to severe drug resistance problems. In this study, in vitro antifungal and antibiofilm activities as well as killing kinetics of the synthesized CuONPs against C. albicans were investigated. Additionally, fungal biofilm was observed by using confocal laser scanning microscopy. The results showed that the pH of the synthesis reaction played an important role in the physicochemical properties and antifungal activities of the obtained CuONPs. CuONPs synthesized at pH 10 and 12 showed the relatively small and narrow size distribution with high negative zeta potential and time-dependent killing kinetics. Confocal laser scanning microscopy confirms obvious fungal biofilm reduction and increased fungal cell death after exposure to CuONPs. These findings suggest the optimal pH of CuONPs synthesis using C. sappan extract as a reducing agent. The results on antifungal and antibiofilm activities indicate that the obtained CuONPs can be a promising agent for treating fungal infection.

Biological activities of extracts and compounds from Thai Kae-Lae (Maclura cochinchinensis (Lour.) Corner).

BACKGROUND AND AIMS: The purpose of this study was to investigate the biological properties of Kae-Lae (Maclura cochinchinensis (Lour.) Corner), a traditional medicinal plant used in Ayurvedic recipes in Thailand. To achieve this objective, heartwood samples were collected from 12 sources across Thailand. Fractional extracts (n-hexane, ethyl acetate, and ethanol) and the dominant compounds (morin, resveratrol, and quercetin) were examined for their abilities on cytotoxicity, antioxidant, anti-inflammation, and antileukaemic activity (Wilms' tumour 1 protein was used as a well-known biomarker for leukaemic cell proliferation). METHODS: The study used MTT to assess cytotoxicity in leukaemic cells (K562, EoL-1, and KG-1a). Antioxidant activities were evaluated using ABTS, DPPH, and FRAP assays. The anti-inflammatory activity was investigated by detecting IL-2, TNF-α, and NO using appropriate detection kits. Wilms' tumour 1 protein expression was measured by Western blotting to determine the anti-leukaemic activity. The inhibition of cell migration was also analyzed to confirm anticancer progression. RESULTS: Among the tested extract fraction, ethyl acetate No. 001 displayed strong cytotoxicity specifically in EoL-1 cells, while n-hexane No. 008 demonstrated this effect in three cell lines. Resveratrol, on the other hand, displayed cytotoxicity in all the tested cells. Additionally, the three major compounds, morin, resveratrol, and quercetin, exhibited significant antioxidant and anti-inflammatory properties. In particular, resveratrol demonstrated a noteworthy decreased Wilms' tumour 1 protein expression and a reduction in cell proliferation across all cells. Moreover, ethyl acetate No. 001, morin, and resveratrol effectively inhibited MCF-7 cell migration. None of these compounds showed any impact on red blood cell haemolysis. CONCLUSION: Based on these findings, it can be concluded that Kae-Lae has promising chemotherapeutic potential against leukaemic cells, with fractional extracts (ethyl acetate and n-hexane) and resveratrol exhibiting the most potent cytotoxic, antioxidant, anti-inflammatory, and anti-cell migration activities.

Antioxidant, antiglycation, and anti-inflammatory activities of Caesalpinia mimosoides.

Oxidative stress, glycation and inflammation are the main causes of many severe diseases. To date, no single extract has been shown to simultaneously inhibit these three reactions. In this study, the antioxidant, antiglycation and anti-inflammatory activities of ethanol extracts from four edible plants that are commonly used as Thai folk medicine were compared. Among these extracts, Caesalpinia mimosoides extract (CME) showed the highest antioxidant potential with Trolox equivalent antioxidant activity (TEAC) of 5.9 ± 0.1 mM/mg followed closely by Zingiber officinale extract (ZOE) with a TEAC value of 5.4 ± 0.2 mM/mg. However, CME showed no cytotoxicity, whereas ZOE greater than 60 µg/mL showed cytotoxicity to normal human cells. Antiglycation assay using bovine serum albumin-ribose showed comparable potency between CME and Spondias dulcis extract (SDE). However, CME exhibited a high anti-inflammatory activity, significantly higher than SDE and activity depending on the dose. At a concentration of 60 µg/mL, approximately 85% of the interleukin-6 pro-inflammatory cytokine produced from human monocytes, induced by lipopolysaccharides, was completely inhibited by CME whereas SDE showed no inhibition. In summary, CME is the most potential extract with simultaneously activity of these three reactions. CME has the highest total phenolic content expressed as gallic acid equivalent to 301 ± 8 mg/g. Identification using high-performance liquid chromatography revealed the presence of at least four phenolic compounds, gallic acid, syringic acid, p-coumaric acid, and ellagic acid are existed in CME. Our finding suggests that CME is a promising natural source for inhibition of oxidative stress, glycation, and inflammation.

Antioxidant, Anti-Inflammatory and Attenuating Intracellular Reactive Oxygen Species Activities of Nicotiana tabacum var. Virginia Leaf Extract Phytosomes and Shape Memory Gel Formulation.

Oxidative stress is one of the major causes of skin aging. In this study, the shape memory gels containing phytosomes were developed as a delivery system for Nicotiana tabacum var. Virginia fresh (VFL) and dry (VDL) leaf extracts. The extracts were loaded in the phytosomes by a solvent displacement method. The physical and chemical characteristics and stability of phytosomes were evaluated by dynamic light scattering and phytochemistry, respectively. The in vitro antioxidant activity and intracellular reactive oxygen species reduction of phytosomes and/or extracts were investigated by the DPPH and ABTS radical scavenging assays, FRAP assay, and DCFH-DA fluorescent probe. The cytotoxicity and anti-inflammatory activity of VDL and VFL phytosomes were studied by an MTT and a nitric oxide assay, respectively. Here, we first reported the total phenolic content in the dry leaf extract of N. tabacum var. Virginia was significantly greater than that of the fresh leaf extract. The HPLC analysis results revealed that VDL and VFL extracts contained 4.94 ± 0.04 and 3.13 ± 0.01 µg/mL of chlorogenic acid and 0.89 ± 0.00 and 0.24 ± 0.00 µg/mL of rutin, respectively. The phytosomes of the VDL and VFL extracts displayed stable size, polydispersity index, zeta potential values, and good chemical stability. VDL and VDL phytosomes showed higher phenolic and flavonoid contents which showed stronger DPPH and ABTS radical scavenging effects and reduced the intracellular ROS. The results suggested that the phenolic compounds are the main factor in their antioxidant activity. Both VDL and VFL phytosomes inhibited nitric oxide production induced by LPS, suggesting the anti-inflammatory activity of the phytosomes. The shape memory gel containing VDL and VFL phytosomes had good physical stability in terms of pH and viscosity. The VDL and VFL phytosomes dispersed in the shape memory gels can be considered as a promising therapeutic delivery system for protecting the skin from oxidation and reactive oxygen species.

Doxorubicin-Loaded Polymeric Micelles Conjugated with CKR- and EVQ-FLT3 Peptides for Cytotoxicity in Leukemic Stem Cells.

Doxorubicin (Dox) is the standard chemotherapeutic agent for acute myeloblastic leukemia (AML) treatment. However, 40% of Dox-treated AML cases relapsed due to the presence of leukemic stem cells (LSCs). Thus, poloxamer 407 and CKR- and EVQ-FLT3 peptides were used to formulate Dox-micelles (DMs) and DM conjugated with peptides (CKR and EVQ) for improving AML-LSC treatment. Results indicated that DMs with a weight ratio of Dox to P407 of 1:200 had a particle size of 23.3 ± 1.3 nm with a high percentage of Dox entrapment. They were able to prolong drug release and maintain physicochemical stability. Following effective DM preparation, P407 was modified and conjugated with FLT3 peptides, CKR and EVQ to formulate DM-CKR, DM-EVQ, and DM-CKR+DM-EVQ. Freshly synthesized DMs displaying FLT3 peptides showed particle sizes smaller than 50 nm and a high drug entrapment level, comparable with DMs. DM-CKR+DM-EVQ was considerably more toxic to KG-1a (AML LSC-like cell model) than Dox-HCl. These FLT3-targeted DMs could increase drug uptake and induce apoptosis induction. Due to an increase in micelle-LSC binding and uptake, DMs displaying both peptides tended to improve the potency of Dox compared to a single peptide-coupled micelle.

Imatinib Mesylate-Loaded Rosin/Cinnamon Oil-Based In Situ Forming Gel against Colorectal Cancer Cells.

Localized delivery systems have been typically designed to enhance drug concentration at a target site and minimize systemic drug toxicity. A rosin/cinnamon oil (CO) in situ forming gel (ISG) was developed for the sustainable delivery of imatinib mesylate (IM) against colorectal cancer cells. CO has been claimed to express a potent anticancer effect against various cancer cells, as well as a synergistic effect with IM on colorectal cancer cells; however, poor aqueous solubility limits its application. The effect of rosin with the adding CO was assessed on physicochemical properties and in vitro drug release from developed IM-loaded rosin/CO-based ISG. Moreover, in vitro cytotoxicity tests were conducted against two colorectal cancer cells. All formulations exhibited Newtonian flow behavior with viscosity less than 266.9 cP with easier injectability. The adding of CO decreased the hardness and increased the adhesive force of the obtained rosin gel. The gel formation increased over time under microscopic observation. CO-added ISG had a particle-like gel appearance, and it promoted a higher release of IM over a period of 28 days. All tested ISG formulations revealed cytotoxicity against HCT-116 and HT-29 cell lines at different incubation times. Thus, CO-loaded rosin-based ISG can act as a potentially sustainable IM delivery system for chemotherapy against colorectal cancer cells.

Stereomicroscope with Imaging Analysis: A Versatile Tool for Wetting, Gel Formation and Erosion Rate Determinations of Eutectic Effervescent Tablet.

Wettability, gel formation and erosion behaviors could influence the drug release pattern of solid dosage forms. Typically, these parameters are evaluated using a variety of techniques. Nonetheless, there has been no previous research on versatile tool development for evaluating several tablet characteristics with a single tool. The aim of this study was to develop the versatile tool for measuring various physical properties of eutectic effervescent tablets and also investigate the relationship between these parameters with parameters from drug dissolution. Ibuprofen (IBU)-poloxamer 407 (P407) eutectic effervescent tablets were fabricated with a direct compression method. Their wetting properties, gel formation and erosion behaviors were investigated using a stereomicroscope with imaging analysis in terms of the liquid penetration distance, gel thickness and erosion boundary diameter, respectively. In addition, the dissolution rate (k) and disintegration time of eutectic effervescent tablets in 0.1 N HCl buffer pH 1.2 were also determined. Incorporation of P407 into the IBU tablet improved the tablet wetting properties with increasing liquid penetration distance under stereoscope. CO2 liberation from effervescent agents promoted tablet surface roughness from matrix erosion. The relationship between observed physical properties and disintegration and dissolution parameters suggested that the combination of erosion by effervescent agents and gel formation by P407 had a potential influence on dissolution enhancement of the formulation. Therefore, a developed stereomicroscope with an imaging analysis technique was exhibited as an alternative versatile tool for determining the wetting properties, gel formation and erosion behaviors of pharmaceutical solid dosage forms.