Eucalypt Extracts Prepared by a No-Waste Method and Their 3D-Printed Dosage Forms Show Antimicrobial and Anti-Inflammatory Activity.

The pharmaceutical industry usually utilizes either hydrophobic or hydrophilic substances extracted from raw plant materials to prepare a final product. However, the waste products from the plant material still contain biologically active components with the opposite solubility. The aim of this study was to enhance the comprehensive usability of plant materials by developing a new no-waste extraction method for eucalypt leaves and by investigating the phytochemical and pharmacological properties of eucalypt extracts and their 3D-printed dosage forms. The present extraction method enabled us to prepare both hydrophobic soft extracts and hydrophilic (aqueous) dry extracts. We identified a total of 28 terpenes in the hydrophobic soft extract. In the hydrophilic dry extract, a total of 57 substances were identified, and 26 of them were successfully isolated. The eucalypt extracts studied showed significant antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, Candida albicans, Corynebacterium diphtheriae gravis, and Corynebacterium diphtheriae mitis. The anti-inflammatory activity of the dry extract was studied using a formalin-induced-edema model in mice. The maximum anti-exudative effect of the dry extract was 61.5% at a dose of 20 mg/kg. Composite gels of polyethylene oxide (PEO) and eucalypt extract were developed, and the key process parameters for semi-solid extrusion (SSE) 3D printing of such gels were verified. The SSE 3D-printed preparations of novel synergistically acting eucalypt extracts could have uses in antimicrobial and anti-inflammatory medicinal applications.

Phytochemical, Pharmacological, and Molecular Docking Study of Dry Extracts of Matricaria discoidea DC. with Analgesic and Soporific Activities.

Pineapple weed (Matricaria discoidea DC.) is a widespread plant in Europe and North America. In ethnomedicine, it is well-known for its anti-inflammatory and spasmolytic activities. The aim of this research was to develop novel methods of M. discoidea processing to obtain essential oil and dry extracts and to investigate their phytochemical compositions. Moreover, the molecular docking of the main substances and the in vivo studies on their soporific and analgesic activities were conducted. The essential oil and two dry extracts from M. discoidea were prepared. A total of 16 phenolic compounds (seven flavonoids, seven hydroxycinnamic acids, and two phenolic acids) in the dry extracts were identified by means of UPLC-MS/MS. In the essential oil, nine main terpenoids were identified by gas chromatography (GC). It was shown that phenolic extraction from the herb was successful when using 70% ethanol in a triple extraction method and at a ratio of 1:14-1:16. The in vivo studies with rodents demonstrated the analgesic activity of the M. discoidea extracts and improvements in the sleep of animals. The dry extracts of M. discoidea did not show any toxicity. The molecular docking analysis showed a high probability of COX-1,2 inhibition and NMDA receptor antagonism by the extracts.

Thermodynamic solubility measurement without chemical analysis.

In this work, the optical imaging based single particle analysis (SPA) and the gold standard shake-flask (SF) solubility methods are compared. We show that to analyze pharmaceutical compounds spanning 7 log units in solubility and a diverse chemical space with limited resources, several analytical techniques are required (HPLC-UV, LC-MS, refractometry and UV-Vis spectrometry), whereas solely the SPA method is able to analyze all the same compounds. SPA experiments take only minutes, while for SF, it may take days to reach thermodynamic equilibration. This decreases the time span needed for the solubility experiment from initial preparations to obtaining the result from roughly three days to less than three hours. The optimal particle size for SPA ranges from approximately one to hundreds of microns. Challenges include measuring large particles, very fast dissolving compounds and handling small sample sizes. Inherent exclusion of density from the SPA measurement is a potential source of error for compounds with very low or high density values. The average relative difference of 37 % between the two methods is very good in the realm of solubility, where 400 % interlaboratory reproducibility can be expected.

Phytochemical, Technological, and Pharmacological Study on the Galenic Dry Extracts Prepared from German Chamomile (Matricaria chamomilla L.) Flowers.

Galenic preparations of German chamomile are used to treat mild skin diseases, inflammation, and spasms, and they have also been reported to have anxiolytic and sedative effects. The medicinal use of chamomile is well known in ethnomedicine. After obtaining its galenic preparations, there is lots of waste left, so it is expedient to develop waste-free technologies. The aims of this study were to gain knowledge of the ethnomedical status of chamomile in the past and present, develop methods for preparing essential oils and dry extracts from German chamomile flowers using complex processing, reveal the phytochemical composition of such extracts, and verify the analgesic and soporific activity of the extracts. Two methods for the complex processing of German chamomile flowers were developed, which allowed us to obtain the essential oil and dry extracts of the tincture and aqueous extracts as byproducts. A total of 22 phenolic compounds (7 hydroxycinnamic acids, 13 flavonoids, and 2 phenolic acids) were found in the dry extracts by using UPLC-MS/MS. In total, nine main terpenoids were identified in the chamomile oil, which is of the bisabolol chemotype. During the production of chamomile tincture, a raw material-extractant ratio of 1:14-1:16 and triple extraction are recommended for its highest yield. In in vivo studies with mice and rats, the extracts showed analgesic activity and improvements in sleep. The highest sedative and analgesic effects in rodents were found with the dry extract prepared by using a 70% aqueous ethanol solution for extraction at a dose of 50 mg/kg. The developed methods for the complex processing of German chamomile flowers are advisable for implementation into the pharmaceutical industry to reduce the volume of waste during the production of its essential oil and tincture, and to obtain new products.

Application of nanofiber-based drug delivery systems in improving anxiolytic effect of new 1,2,3-triazolo-1,4-benzodiazepine derivatives.

Anxiety disorders are highly prevalent worldwide and can affect people of all ages, genders and backgrounds. Much efforts and resources have been directed at finding new anxiolytic agents and drug delivery systems (DDSs) especially for cancer patients to enhance targeted drug delivery, reduce drug adverse effects, and provide an analgesic effect. The aim of this study was (1) to design and develop novel nanofiber-based DDSs intended for the oral administration of new 1,2,3-triazolo-1,4-benzodiazepines derivatives, (2) to investigate the physical solid-state properties of such drug-loaded nanofibers, and (3) to gain knowledge of the anxiolytic activity of the present new benzodiazepines in rodents in vivo. The nanofibers loaded with 1,2,3-triazolo-1,4-benzodiazepine derivatives were prepared by means of electrospinning (ES). Field-emission scanning electron microscopy and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy were used for the physicochemical characterization of nanofibers. The anxiolytic activity of new derivatives and drug-loaded nanofibers was studied with an elevated plus maze test and light-dark box test. New 1,2,3-triazolo-1,4-benzodiazepine derivatives showed a promising anxiolytic effect in mice with clear changes in behavioral reactions in both tests. The nanofiber-based DDS was found to be feasible in the oral delivery of the present benzodiazepine derivatives. The nanofibers generated by means of ES presented the diameter in a nanoscale, uniform fiber structure, capacity for drug loading, and the absence of defects. The present findings provide new insights in the drug treatment of anxiety disorders with new benzodiazepine derivatives.

Chemical Composition and Insulin-Resistance Activity of Arginine-Loaded American Cranberry (Vaccinium macrocarpon Aiton, Ericaceae) Leaf Extracts.

One of the key pathogenetic links in type 2 diabetes mellitus (T2DM) is the formation of insulin resistance (IR). Besides a wide selection of synthetic antidiabetic drugs, various plant-origin extracts are also available to support the treatment of T2DM. This study aimed to investigate and gain knowledge of the chemical composition and potential IR correction effect of American cranberry (Vaccinium macrocarpon Aiton) leaf extracts and formulate novel 3D-printed oral dosage forms for such extracts. The bioactivity and IR of L-arginine-loaded cranberry leaf extracts were studied in vivo in rats. The cranberry leaf extracts consisted of quinic, 3-caffeoylquinic (chlorogenic), p-coumaroylquinic acids, quercetin 3-O-galactoside, quercetin-3-O-glucoside, quercetin-3-xyloside, quercetin-3-O-arabino pyranoside, quercetin-3-O-arabinofuranoside, quercetin 3-O-rhamnoside, and quercetin-O-p-coumaroyl hexoside-2 identified by HPLC. In vivo studies with rats showed that the oral administration of the cranberry leaf extracts had a positive effect on insulin sensitivity coefficients under the insulin tolerance test and affected homeostasis model assessment IR levels and liver lipid content with experimental IR. A novel 3D-printed immediate-release dosage form was developed for the oral administration of cranberry leaf extracts using polyethylene oxide as a carrier gel in semi-solid extrusion 3D printing. In conclusion, American cranberry leaf extracts loaded with L-arginine could find uses in preventing health issues associated with IR.

High Boron Content Enhances Bioactive Glass Biodegradation.

Derived Hench bioactive glass (BaG) containing boron (B) is explored in this work as it plays an important role in bone development and regeneration. B was also found to enhance BaG dissociation. However, it is only possible to incorporate a limited amount of B. To increase the amount of B in BaG, bioactive borosilicate glasses (BaG-Bx) were fabricated based on the use of the solution-gelation process (sol-gel). In this work, a high B content (20 wt.%) in BaG, respecting the conditions of bioactivity and biodegradability required by Hench, was achieved for the first time. The capability of BaG-Bx to form an apatite phase was assessed in vitro by immersion in simulated body fluid (SBF). Then, the chemical structure and the morphological changes in the fabricated BaG-Bx (x = 0, 5, 10 and 20) were studied. The formation of hydroxyapatite (HAp) layer was observed with X-ray diffraction (XRD) and infrared (IR) spectroscopy. The presence of HAp layer was confirmed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Enhanced bioactivity and chemical stability of BaG-Bx were evaluated with an ion exchange study based on Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES) and energy dispersive spectroscopy (EDS). Results indicate that by increasing the concentration of B in BaG-Bx, the crystallization rate and the quality of the newly formed HAp layer on BaG-Bx surfaces can be improved. The presence of B also leads to enhanced degradation of BaGs in SBF. Accordingly, BAG-Bx can be used for bone regeneration, especially in children, because of its faster degradation as compared to B-free glass.

Pharmaceutical 3D-printing of nanoemulsified eucalypt extracts and their antimicrobial activity.

Overcoming the health threatening consequences of staphylococcal infections and their negative socio-economic effects have become a priority in the medical, pharmaceutical, food and many other sectors globally. Staphylococcal infections are a big challenge for a global health care, since they are difficult to be diagnosed and treated. Therefore, the development of new medicinal products of plant-origin is timely and important, because bacteria have a limited ability to develop resistance to such products. In the present study, a modified eucalypt (Eucalyptus viminalis L.) extract was prepared and further enhanced by using different excipients (surface active agents) to obtain a water-miscible 3D-printable extract (nanoemulsified aqueous eucalypt extract). Phytochemical and antibacterial studies of the eucalypt leaves extracts were conducted as a preliminary investigation for 3D-printing experiments of the extracts. The nanoemulsified aqueous eucalypt extract was mixed with polyethylene oxide (PEO) to form a gel applicable for semi-solid extrusion (SSE) 3D printing. The key process parameters in a 3D-printing process were identified and verified. The printing quality of the 3D-lattice type eucalypt extract preparations was very good, demonstrating the feasibility of using an aqueous gel in SSE 3D printing also exhibiting compatibility of the carrier polymer (PEO) with the plant extract. The SSE 3D-printed eucalypt extract preparations presented a rapid dissolution in water within 10-15 min, suggesting the applicability of these preparations e.g., in oral immediate-release applications.

Essential Oil-Loaded Nanofibers for Pharmaceutical and Biomedical Applications: A Systematic Mini-Review.

Essential oils (EOs) have been widely exploited for their biological properties (mainly as antimicrobials) in the food industry. Encapsulation of EOs has opened the way to the utilization of EOs in the pharmaceutical and biomedical fields. Electrospinning (ES) has proved a convenient and versatile method for the encapsulation of EOs into multifunctional nanofibers. Within the last five years (2017-2022), many research articles have been published reporting the use of ES for the fabrication of essential oil-loaded nanofibers (EONFs). The objective of the present mini-review article is to elucidate the potential of EONFs in the pharmaceutical and biomedical fields and to highlight their advantages over traditional polymeric films. An overview of the conventional ES and coaxial ES technologies for the preparation of EONFs is also included. Even though EONFs are promising systems for the delivery of EOs, gaps in the literature can be recognized (e.g., stability studies) emphasizing that more research work is needed in this field to fully unravel the potential of EONFs.

Fast imaging-based single particle analysis method for solubility determination.

The solubility and dissolution rates of chemical compounds are crucial properties in several fields of industry and research. However, accurate, rapid and green methods for their measurement, which only consume micrograms of compound, are lacking. Here, the unique approach of non-specific, image-based single particle analysis (SPA) for solubility testing is directly compared to and thus validated on the mid-solubility range with the current gold standard shake-flask method with UV-Vis spectroscopy employed for determining sample concentrations. Five biologically active compounds representing a range of physicochemical properties including pKa and logP were analyzed with both methods. The comparison of SPA and the shake-flask (SF) analysis shows excellent linear correlation (R2 = 0.99). Higher variability of the SPA method is attributed to variability between the properties of individual particles, which cannot be detected with traditional methods. Due to the similar average solubility values compared to those produced with SF, it is concluded that the SPA method has great potential as an analytical tool for small-scale solubility studies. It also has several practical advantages over the current gold standard shake-flask method, such as speed, low consumables consumption, and no requirement for prior knowledge of compound chemistry.

Identifying Potential Drug-Related Problems Among Geriatric Patients With Use of an Integrated Clinical Decision Support Tool.

Background: Drug-related problems (DRPs) which arise from potentially inappropriate medications (PIMs) are a common problem in older people with multi-morbidity and polypharmacy. Aim: To develop an integrated PIM clinical decision support tool for identification of DRPs in geriatric multi-morbid polypharmacy patients, using the EU(7)-PIM and EURO-FORTA lists, with a focus on high-risk medications. Methods: The integrated PIM tool used the information on PIMs in both databases-the EU(7)-PIM and EURO-FORTA. PIMs were classified into four color groups based on risk profile: high-risk PIMs (should be avoided in older patients) as red, moderate-risk PIMs (require dose and/or treatment duration adjustment) as yellow, low-risk PIMs (low DRP risk) as green, and questionable PIMs (incomplete/missing information) as grey. Results: The summarized list of the high-risk (red and some grey) PIMs contained 81 active substances and medication classes. According to the ATC classification, most of the high-risk PIMs (n = 60, 74.1%) belong to the A, C, and N medication groups and 50.6% (n = 41) of the high-risk PIMs have currently marketing authorization in Estonia. The preliminary list of the moderate- and low-risk (yellow, green, and other grey) PIMs contained 240 active substances and medication classes, but sub-classification of this category into one or another group depends mainly on an individual patient´s clinical characteristics in a concrete analyzed study sample and needs further research. Conclusion: The integrated clinical decision support tool based on the EU(7)-PIM and EURO-FORTA criteria addresses the need for more efficient identification of DRPs. It can be applied to identify PIMs and geriatric prescribing problems in different health care settings, and also in a context of little clinical information available.

Physicomechanical characterization and tablet compression of theophylline nanofibrous mats prepared by conventional and ultrasound enhanced electrospinning.

Theophylline (TEO) nanofibers with polyethylene oxide (PEO) were prepared by conventional electrospinning (ES) and novel needleless ultrasound-enhanced electrospinning (USES). They were compared for Young's modulus, elongation at rupture and rupture stress, tabletability and drug release. Placebo (PEO) or drug-loaded (PEO/TEO 90:10) nanofibers were examined by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and infrared spectroscopy (ATR-FTIR). Nanofibers prepared by USES were thinner than ES nanofibers and drug-loaded nanofibers thinner than placebo. Drug was mostly amorphous and interacted weakly with PEO. Mats generated by USES and also drug-loaded mats demonstrated higher Young's modulus (stiffness) and higher rupture stress. Under compression, USES and drug-loaded nanofibers demonstrated greater compaction work, higher yield pressure (Heckel and K-L models), and produced stronger tablets than ES and placebo respectively. Principal Component Analysis revealed two significant components explaining 91.05% of the variance. The first comprised the compaction work, yield pressure (ductility) and Young's modulus that were positively intercorrelated and elongation at rupture that was correlated negatively. The second comprised the mat rupture stress and tablet breaking load. Drug release from nanofibrous tablets was faster than tablets of physical mixture but there was no difference between the tablets of the two electrospinning methods.

Berberine-loaded liposomes for oral delivery: Preparation, physicochemical characterization and in-vivo evaluation in an endogenous hyperlipidemic animal model.

Berberine (BBR) is a plant-origin quaternary isoquinoline alkaloid presenting exogenous cholesterol lowering and anti-hyperlipidemia therapeutic effects. The aim of this study was to design and generate BBR-loaded proliposomes (PLs) as solid templates for high-dose liposomes and consequently, to enhance the oral bioavailability and therapeutic effect of BBR. An air-suspension coating (layering) method was used for generating BBR-loaded PLs. The size, distribution size, morphology, and entrapment efficiency (EE) of the final reconstituted liposomes were assessed. The oral bioavailability and endogenous cholesterol lowering effects of BBR loaded in liposomes were investigated in rats and mice, respectively. The BBR-loaded PLs showed a smooth BBR-embedded film around micron-scale carrier particles (mannitol). The reconstituted BBR-loaded liposomes had a nano-scale average size (116.6 ± 5.8 nm), narrow size distribution (polydispersity index, PDI 0.269 ± 0.038), and high EE (87.8 ± 1.0%). The oral bioavailability of reconstituted BBR-loaded liposomes at a dose of 100 mg/kg in rats was increased even 628% compared to that obtained with pure BBR (according to 90% confidence interval). The BBR-loaded liposomes at the daily oral dose 100 mg/kg in P-407- reduced total cholesterol, triglycerides and low-density lipoprotein cholesterol (LDL-C) in hyperlipidemic mice by 15.8%, 38.2%, and 57.0%, respectively.

Spray Drying of Chitosan Acid Salts: Process Development, Scaling Up and Physicochemical Material Characterization.

We investigated a spray drying process for preparing water-soluble salts of high molecular weight chitosan (CH) intended for pharmaceutical excipient applications. CH was derived from chitin of marine lobster origin (Panulirus argus). The effects of organic acid (acetic or lactic acid) and the ratio (difference) of inlet/outlet air temperature (140/90 °C or 160/100 °C) on spray drying were studied. The yield of spray-dried CH salt powders ranged from 50% to 99% in laboratory and industrial-scale processes. The spray-dried dry powder of CH salts consisted of spherical agglomerated particles with an average diameter of 36.2 ± 7.0 µm (CH acetate) and 108.6 ± 11.5 µm (CH lactate). After dispersing the spray-dried CH salt powder samples in purified water, the mean particle sizes obtained for the CH acetate salts were 31.4 nm (batch A001), 33.0 nm (A002) and 44.2 nm (A003), and for the CH lactate salts 100.8 nm (batch L001), 103.2 nm (L002) and 121.8 nm (L003). The optimum process conditions for spray drying were found: an inlet air temperature of 160 ± 5 °C, an outlet temperature of 100 ± 5 °C and an atomizer disk rotational speed of 18,200 min-1. The X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) results confirmed the amorphous state of the CH salts. The 1H nuclear magnetic resonance (NMR) and Fourier transform infrared (FT-IR) spectra of CH acetate and lactate salts verified that the spray drying process does not affect the polymer backbone. In conclusion, both laboratory and industrial-scale spray drying methods for preparing water-soluble acid salts of CH are reproducible, and the physicochemical properties of the corresponding CH acid salts are uniform.

Nanoformulation and Evaluation of Oral Berberine-Loaded Liposomes.

Berberine (BBR) is a poorly water-soluble quaternary isoquinoline alkaloid of plant origin with potential uses in the drug therapy of hypercholesterolemia. To tackle the limitations associated with the oral therapeutic use of BBR (such as a first-pass metabolism and poor absorption), BBR-loaded liposomes were fabricated by ethanol-injection and thin-film hydration methods. The size and size distribution, polydispersity index (PDI), solid-state properties, entrapment efficiency (EE) and in vitro drug release of liposomes were investigated. The BBR-loaded liposomes prepared by ethanol-injection and thin-film hydration methods presented an average liposome size ranging from 50 nm to 244 nm and from 111 nm to 449 nm, respectively. The PDI values for the liposomes were less than 0.3, suggesting a narrow size distribution. The EE of liposomes ranged from 56% to 92%. Poorly water-soluble BBR was found to accumulate in the bi-layered phospholipid membrane of the liposomes prepared by the thin-film hydration method. The BBR-loaded liposomes generated by both nanofabrication methods presented extended drug release behavior in vitro. In conclusion, both ethanol-injection and thin-film hydration nanofabrication methods are feasible for generating BBR-loaded oral liposomes with a uniform size, high EE and modified drug release behavior in vitro.

Preparation and characterization of hot-melt extruded polycaprolactone-based filaments intended for 3D-printing of tablets.

Hot-melt extruded (HME) filaments are an essential intermediate product for the three- dimensional (3D) printing of drug delivery systems (DDSs) by the fused deposition modelling (FDM) process. The aim of this study was to design novel polymeric 3D-printable HME filaments loaded with active pharmaceutical ingredients (APIs). The physical solid-state properties, mechanical properties, drug release and short-term storage stability of the filaments and 3D-printed DDSs were studied. Physical powder mixtures of polycaprolactone (PCL), plasticizer and API were manually blended, extruded by a single-screw extruder, and printed by a table-top FDM 3D-printing system. The composition of PCL and arabic gum (ARA) enabled the incorporation of 20%, 30% and 40% (w/w) of indomethacin (IND) and theophylline (THEO) into the HME filaments. The uneven distribution of API throughout the filaments impaired 3D printing. The HME filaments loaded with 20% IND or THEO were selected for the further analysis and printing tests (the ratio of PCL, ARA and IND or THEO was 7:1:2, respectively). The IND filaments were yellowish, mechanically strong and flexible, and they had a uniform filament diameter and smooth outer surface. The filaments containing THEO were smooth and off-white. The 3D-printed tablets fabricated from IND or THEO-loaded filaments showed sustained drug release in vitro. The drug release rate, however, significantly increased by changing the geometry of 3D-printed tablets from a conventional tablet structure to an unorthodox lattice ("honeycomb") structure. Overall, the combination of PCL and ARA provides an interesting novel polymeric carrier system for 3D-printable HME filaments and tablets.

USE OF ARTIFICIAL CELLS AS DRUG CARRIERS.

Cells are the fundamental functional units of biological systems and mimicking their size, function and complexity is a primary goal in the development of new therapeutic strategies. Recent advances in chemistry, synthetic biology and material science have enabled the development of cell membrane-based drug delivery systems (DDSs), often referred to as "artificial cells" or protocells. Artificial cells can be made by removing functions from natural systems in a top-down manner, or assembly from synthetic, organic or inorganic materials, through a bottom-up approach where simple units are integrated to form more complex structures. This review covers the latest advances in the development of artificial cells as DDSs, highlighting how their designs have been inspired by natural cells or cell membranes. Advancement of artificial cell technologies has led to a set of drug carriers with effective and controlled release of a variety of therapeutics for a range of diseases, and with increasing complexity they will have a greater impact on therapeutic designs.

Flavonoids and alkaloids from the rhizomes of Zephyranthes ajax Hort. and their cytotoxicity.

A new flavanol derivative, (2R,3R)-3-acetoxy-7-hydroxy-3',4'-methylenedioxyflavan (1), was co-isolated from the rhizomes of Zephyranthes ajax Hort. with the following seven known compounds: 7-hydroxyflavan (2), 7,4'-dihydroxyflavan (3), 7,4'-dihydroxy-8-methylflavan (4), 7,3'-dihydroxy-4'-methoxyflavan (5), 5,4'-dihydroxy-7-methoxy-6-methylflavan (6), 7-hydroxy-3',4'-methylenedioxyflavanone (7) and haemanthamine (8). Their structures were elucidated by combining 1D-/2D-NMR, CD, UV and HRESIMS data, and comparisons with reported data in literature were made. Among these known compounds, 2, 3, 4, 6 and 7 were isolated from the genus Zephyranthes for the first time. In addition, the cytotoxicity assay indicated that compound 8 has potent cytotoxic activity against human hepatocellular carcinoma (the HepG2 cell line), human lung carcinoma (the SK-LU-1 cell line), human carcinoma in the mouth (the KB cell line), human colon carcinoma (the SW480 cell line) and human stomach gastric adenocarcinoma (the AGS cell line), with IC50 values ranging from 4.4 to 11.3 µM. This is the first study reporting the cytotoxicity of compound 8 against the SK-LU-1 cancer cell lines.

chiro-Inositol Derivatives from Chisocheton paniculatus Showing Inhibition of Nitric Oxide Production.

Six new chiro-inositol derivatives (1-6) were isolated from the leaves of Chisocheton paniculatus collected in Vietnam. Their chemical structures were elucidated by 1D and 2D NMR and HRESIMS analyses. All isolated compounds were evaluated for their inhibitory activity against lipopolysaccharide-induced nitric oxide (NO) production in the RAW 264.7 macrophage cell line. Compound 4 exhibited potent inhibitory activity for NO production with an IC50 value of 7.1 µM.

Preformulation Study of Electrospun Haemanthamine-Loaded Amphiphilic Nanofibers Intended for a Solid Template for Self-Assembled Liposomes.

Haemanthamine (HAE) has been proven as a potential anticancer agent. However, the therapeutic use of this plant-origin alkaloid to date is limited due to the chemical instability and poorly water-soluble characteristics of the agent. To overcome these challenges, we developed novel amphiphilic electrospun nanofibers (NFs) loaded with HAE, phosphatidylcholine (PC) and polyvinylpyrrolidone (PVP), and intended for a stabilizing platform (template) of self-assembled liposomes of the active agent. The NFs were fabricated with a solvent-based electrospinning method. The chemical structure of HAE and the geometric properties, molecular interactions and physical solid-state properties of the NFs were investigated using nuclear magnetic resonance (NMR) spectroscopy, scanning electron microscopy (SEM), photon correlation spectroscopy (PCS), Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC), respectively. An in-house dialysis-based dissolution method was used to investigate the drug release in vitro. The HAE-loaded fibers showed a nanoscale size ranging from 197 nm to 534 nm. The liposomes with a diameter between 63 nm and 401 nm were spontaneously formed as the NFs were exposed to water. HAE dispersed inside liposomes showed a tri-modal dissolution behavior. In conclusion, the present amphiphilic NFs loaded with HAE are an alternative approach for the formulation of a liposomal drug delivery system and stabilization of the liposomes of the present alkaloid.