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This work combines natural polymers with nanoemulsions (NEs) to formulate nanocomposites as innovative wound dressing. Spray drying has been used to produce alginate-pectin in situ gelling powders as carriers for NEs loaded with curcumin (CCM), a model antimicrobial drug. The influence of NEs encapsulation in polymer-based microparticles was studied in terms of particle size distribution, morphology, and stability after spray drying. NEs loading did not affect the size of microparticles which was around 3.5 µm, while the shape and surface morphology analyzed using scanning electron microscope (SEM), changed from irregular to spherical. Nanocomposites as dried powders were able to form a gel in less than 5 minutes when in contact with simulated wound fluid (SWF), while the value of moisture transmission of the in situ formed hydrogels allowed to promote good wound transpiration. Moreover, rheologic analyses showed that in situ formed gels loaded with NEs appeared more elastic than blank formulations. The in situ formed gel allowed the prolonged release of CCM-loaded NEs in the wound bed, reaching 100% in 24 hours. Finally, powders cytocompatibility was confirmed by incubation with keratinocyte cells (HaCaT), proving that such nanocomposites can be considered a potential candidate for wound dressings.

At present, the use of benzimidazole drugs in veterinary medicine is strongly limited by both pharmacokinetics and formulative issues. In this research, the possibility of applying an innovative semi-solid extrusion 3D printing process in a co-axial configuration was speculated, with the aim of producing a new gastro-retentive dosage form loaded with ricobendazole. To obtain the drug delivery system (DDS), the ionotropic gelation of alginate in combination with a divalent cation during the extrusion was exploited. Two feeds were optimized in accordance with the printing requirements and the drug chemical properties: the crosslinking ink, i.e., a water ethanol mixture containing CaCl2 at two different ratios 0.05 M and 0.1 M, hydroxyethyl cellulose 2% w/v, Tween 85 0.1% v/v and Ricobendazole 5% w/v; and alginate ink, i.e., a sodium alginate solution at 6% w/v. The characterization of the dried DDS obtained from the extrusion of gels containing different amounts of calcium chloride showed a limited effect on the ink extrudability of the crosslinking agent, which on the contrary strongly influenced the final properties of the DDS, with a difference in the polymeric matrix toughness and resulting effects on floating time and drug release.

Gastric cancer is considered one of the most common malignancies in humans and Helicobacter pylori infection is the major environmental risk factor of gastric cancer development. Given the high spread of this bacterium whose infection is mostly asymptomatic, H. pylori colonization persists for a long time, becoming chronic and predisposing to malignant transformation. The first defensive barrier from bacterial infection is constituted by the gastric mucosa that secretes several protective factors, among which is the trefoil factor 1 (TFF1), that, as mucin 5AC, binds the bacterium. Even if the protective role of TFF1 is well-documented, the molecular mechanisms that confer a beneficial function to the interaction among TFF1 and H. pylori remain still unclear. Here we analyze the effects of this interaction on H. pylori at morphological and molecular levels by means of microscopic observation, chemiotaxis and motility assays and real-time PCR analysis. Our results show that TFF1 favors aggregation of H. pylori and significantly slows down the motility of the bacterium across the mucus. Such aggregates significantly reduce both flgE and flaB gene transcription compared with bacteria not incubated with TFF1. Finally, our results suggest that the interaction between TFF1 and the bacterium may explain the frequent persistence of H. pylori in the human host without inducing disease.

Polysaccharide-based hydrogel particles (PbHPs) are very promising carriers aiming to control and target the release of drugs with different physico-chemical properties. Such delivery systems can offer benefits through the proper encapsulation of many drugs (non-steroidal and steroidal anti-inflammatory drugs, antibiotics, etc) ensuring their proper release and targeting. This review discusses the different phases involved in the production of PbHPs in pharmaceutical technology, such as droplet formation (SOL phase), sol-gel transition of the droplets (GEL phase) and drying, as well as the different methods available for droplet production with a special focus on prilling technique. In addition, an overview of the various droplet gelation methods with particular emphasis on ionic cross-linking of several polysaccharides enabling the formation of particles with inner highly porous network or nanofibrillar structure is given. Moreover, a detailed survey of the different inner texture, in xerogels, cryogels or aerogels, each with specific arrangement and properties, which can be obtained with different drying methods, is presented. Various case studies are reported to highlight the most appropriate application of such systems in pharmaceutical field. We also describe the challenges to be faced for the breakthrough towards clinic studies and, finally, the market, focusing on the useful approach of safety-by-design (SbD).

An extract obtained from hazelnut shells by-products (HSE) has antioxidant and chemopreventive effects on human melanoma and cervical cancer cell lines, inducing apoptosis by caspase-3 activation. A clinical translation is limited by poor water solubility and low bioavailability. Dried plant extracts often show critical characteristics such as sticky/gummy appearance, unpleasant smell, and instability involving practical difficulties in processing for industrial use. A spray drying method has been applied to transform raw HSE in a microparticulate powder. The biopolymeric matrix was based on l-proline as loading carrier, hydroxyethylcellulose in combination with pectin as coating polymers, lecithin and ethanol were used as solubility enhancers. A Hot-Cold-Hot method was selected to prepare the liquid feed. The thus prepared powder showed good technological properties (solid-state, particle dimensions, morphology, and water dissolution rate), stability, and unchanged chemopreventive effects with respect to the unprocessed HSE.

Core-shell beads loaded with betamethasone were developed using co-axial prilling as production technique and pectin plus alginate as polymeric carriers. During this study, many operative conditions were intensively investigated to find the best ones necessary to produce uniform core-shell particle systems in a reproducible way. Particularly, feed solutions&rsquo, composition, polymers mass ratios and the effect of the main process parameters on particles production, micromeritics, inner structure, drug loading and drug-release/swelling profiles in simulated biological fluids were studied. The optimized core-shell formulation F5 produced with a pectin core concentration of 4.0% w/v and an alginate shell concentration of 2.0% w/v (2:1 core:shell ratio) acted as a sustained drug delivery system. It was able to reduce the early release of the drug in the upper part of the gastro-intestinal tract for the presence of the zinc-alginate gastro-resistant outer layer and to specifically deliver it in the colon, thanks to the selectivity of amidated low methoxy pectin core for this district. Therefore, these particles may be proposed as colon targeted drug delivery systems useful for inflammatory bowel disease (IBD) therapy.

In this paper, alginate-pectin blend particles loaded with Annexin A1 derived peptide Ac2-26 as an in situ forming dressing was successfully developed for wound repair applications. High mannuronic (M) content alginate and amidated pectin blend have been used to encapsulate Ac2-26 in order to enhance stability of the peptide at room temperature and to control its release through the in situ formed gel. Ac2-26 recovery and FTIR studies suggests chemical interactions between peptide and polysaccharides blend able to improve the encapsulation efficiency of Ac2-26 into the polymer matrix and control its release, till 48 h. In vitro wound healing assay on HaCaT cells highlights the ability of Ac2-26 to significantly accelerate wound healing compared to unloaded particles, with complete closure of the wound model in 24 h. Therefore, all these results suggest that Ac2-26 loaded submicrometric in situ gelling powders could be a promising wound dressing to improve wound care armamentarium.

Processing and shaping of dried gels are of interest in several fields like alginate aerogel beads used as highly porous and nanostructured particles in biomedical applications. The physicochemical properties of the alginate source, the solvent used in the gelation solution and the gel drying method are key parameters influencing the characteristics of the resulting dried gels. In this work, dried gel beads in the form of xerogels, cryogels or aerogels were prepared from alginates of different molecular weights (120 and 180 kDa) and concentrations (1.25, 1.50, 2.0 and 2.25% (w/v)) using different gelation conditions (aqueous and ethanolic CaCl2 solutions) and drying methods (supercritical drying, freeze-drying and oven drying) to obtain particles with a broad range of physicochemical and textural properties. The stability of physicochemical properties of alginate aerogels under storage conditions of 25 &deg, C and 65% relative humidity (ICH-climatic zone II) during 1 and 3 months was studied. Results showed significant effects of the studied processing parameters on the resulting alginate dried gel properties. Stability studies showed small variations in aerogels weight and specific surface area after 3 months of storage, especially, in the case of aerogels produced with medium molecular weight alginate.

The aim of this research was to develop a robust process capable of producing soft-capsules with hydrophilic core for topical administration by means of an inverse gelation. While this method is extensively studied to prepare particles with oily content, its knowledge space in the case of the proposed application is limited. Therefore, a half-fractional factorial design with 5 factors at two levels with resolution V was employed, to meet the scientific requirements in accordance with the Quality by Design approach. Kojic acid, an unstable skin whitening agent, was selected as the active ingredient for its easy detectability. Soft-capsules where produced through a vibrating nozzle device, dripping a thickened calcium chloride solution into an alginate bath. The experimental design applied revealed the effect of several Critical Process Parameters such as the solution's composition, frequency and flow-rate onto Critical Quality Attributes of the produced soft-capsules as for example drug content, encapsulation efficiency, size, shape and mechanical strength. The overall knowledge gained through the DoE exercise showed that the inverse gelation process was capable of producing soft-capsules with the desired attributes, resistant enough to allow handling during storage, but also easily ruptured when applied onto the skin, without leaving residues.

Fused deposition modeling by 3D-printing is a rapid technique for the production of personalized drug dosage forms. One of the most delicate step of the whole process is the drug loading onto the thermoplastic polymer to obtain the drug-loaded filament used as feedstock for 3D FDM printers. With the aim of improving the drug loading, a systematic study on the influence of polymer size distribution on the quantity of drug able to adhere onto the polymer surface was conducted. Several solid mixtures were prepared, using five PVA batches (4000-5000 µm, 1000-2000 µm, 600-1000 µm, 250-600 µm,250 µm) and Ciprofloxacin hydrochloride as active compound in different ratios. Operative specifics and printer's parameters were tuned for an optimal print of drug-loaded filaments into the desired dosage forms, i.e. cylindrical printlets, fully characterized in terms of homogeneity, process efficiency, physical properties, drug content and release kinetics. The PVA particle size affected the polymer ability to form homogeneous mixture with the drug and the efficiency of the extrusion process. In particular, finest PVA batches showed better processability and reduced the drug loss during the drug/polymer mixing and the extrusion process. Drug-loaded filaments with different drug concentrations were successfully printed and the obtained printlets dissolution profiles were almost superimposable, taking an important step for the future application of 3D-printing manufacturing process to obtain personalized galenic formulations.

Numerous studies have been focused on hydrophobic compounds encapsulation as oils. In fact, oils can provide numerous health benefits as synergic ingredient combined with other hydrophobic active ingredients. However, stable microparticles for pharmaceutical purposes are difficult to achieve when commonly techniques are used. In this work, sunflower oil was encapsulated in calcium-alginate capsules by prilling technique in co-axial configuration. Core-shell beads were produced by inverse gelation directly at the nozzle using a w/o emulsion containing aqueous calcium chloride solution in sunflower oil pumped through the inner nozzle while an aqueous alginate solution, coming out from the annular nozzle, produced the beads shell. To optimize process parameters artificial intelligence tools were proposed to optimize the numerous prilling process variables. Homogeneous and spherical microcapsules with narrow size distribution and a thin alginate shell were obtained when the parameters as w/o constituents, polymer concentrations, flow rates and frequency of vibration were optimized by two commercial software, FormRules® and INForm®, which implement neurofuzzy logic and Artificial Neural Networks together with genetic algorithms, respectively. This technique constitutes an innovative approach for hydrophobic compounds microencapsulation.

Cellular vesicles are membrane-enclosed organelles that transport material inside and outside the cell. Plant-derived vesicles are receiving increasing attention due to their potential as nanovectors for the delivery of biologically active substances. We aimed to expand our understanding about the heterogeneity and the protein biocargo of citrus fruit juice sac cell-derived vesicles. Micro- and nano-sized vesicle fractions were isolated from four citrus species, C. sinensis, C. limon, C. paradisi and C. aurantium, characterized using physicochemical methods and protein cargos were compared using label-free quantitative shotgun proteomics. In each sample approximately 600-800 proteins were identified. Orthologues of most of the top-ranking proteins have previously been reported in extracellular vesicles of mammalian origin. Patellin-3-like, clathrin heavy chain, heat shock proteins, 14-3-3 protein, glyceraldehyde-3-phosphate dehydrogenase and fructose-bisphosphate aldolase 6 were highly expressed in all citrus vesicle fractions. The presence of membrane channel aquaporin on the other hand characteristic of the nanovesicle fractions. Bioinformatics revealed more than hundred protein orthologues potentially implicated in vesicular trafficking. In particular, CCV, COPI and COPII coat proteins indicates the presence of highly heterogeneous populations of intracellular transport vesicles. Moreover, the different hydrolases and oxidoreductases transported within the citrus fruit-derived vesicles can be responsible for the various biological activities possessed by the preparations.

Cellular vesicles are membrane-enclosed organelles that transport material inside and outside the cell. Plant-derived vesicles are receiving increasing attention due to their potential as nanovectors for the delivery of biologically active substances. We aimed to expand our understanding about the heterogeneity and the protein biocargo of citrus fruit juice sac cell-derived vesicles. Micro- and nanosized vesicle fractions were isolated from four citrus species,C. sinensis,C. limon,C. paradisiandC. aurantium, characterized using physicochemical methods and protein cargos were compared using label-free quantitative shotgun proteomics. In each sample approximately 600-800 proteins were identified. Orthologues of most of the top-ranking proteins have previously been reported in extracellular vesicles of mammalian origin. Patellin-3-like, clathrin heavy chain, heat shock proteins, 14-3-3 protein, glyceraldehyde-3-phosphate dehydrogenase and fructose-bisphosphate aldolase 6 were highly expressed in all citrus vesicle fractions. The presence of membrane channel aquaporin on the other hand characteristic of the nanovesicle fractions. Bioinformatics revealed more than hundred protein orthologues potentially implicated in vesicular trafficking. In particular, CCV, COPI and COPII coat proteins indicates the presence of highly heterogeneous populations of intracellular transport vesicles. Moreover, the different hydrolases and oxidoreductases transported within the citrus fruit-derived vesicles can be responsible for the various biological activities possessed by the preparations.AbbreviationsEVsextracellular vesicles;MVsmicrovesicles;NVsnanovesicles;PMplasma membrane;UCultracentrifugation;CCVclathrin coated vesicles;COPIcoat protein I;COPIIcoat protein II

Hazelnut shells, a by-product of the kernel industry processing, are reported to contain high amount of polyphenols. However, studies on the chemical composition and potential effects on human health are lacking. A methanol hazelnut shells extract was prepared and dried. Our investigation allowed the isolation and characterization of different classes of phenolic compounds, including neolignans, and a diarylheptanoid, which contribute to a high total polyphenol content (193.8 ± 3.6 mg of gallic acid equivalents (GAE)/g of extract). Neolignans, lawsonicin and cedrusin, a cyclic diarylheptanoid, carpinontriol B, and two phenol derivatives, C-veratroylglycol, and β-hydroxypropiovanillone, were the main components of the extract (0.71%–2.93%, w/w). The biological assays suggested that the extract could be useful as a functional ingredient in food technology and pharmaceutical industry showing an in vitro scavenging activity against the radical 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) (EC50 = 31.7 μg/mL with respect to α-tocopherol EC50 = 10.1 μg/mL), and an inhibitory effect on the growth of human cancer cell lines A375, SK-Mel-28 and HeLa (IC50 = 584, 459, and 526 μg/mL, respectively). The expression of cleaved forms of caspase-3 and poly(ADP-ribose) polymerase-1 (PARP-1) suggested that the extract induced apoptosis through caspase-3 activation in both human malignant melanoma (SK-Mel-28) and human cervical cancer (HeLa) cell lines. The cytotoxic activity relies on the presence of the neolignans (balanophonin), and phenol derivatives (gallic acid), showing a pro-apoptotic effect on the tested cell lines, and the neolignan, cedrusin, with a cytotoxic effect on A375 and HeLa cells.

Cystic fibrosis (CF) lungs are usually susceptible to Pseudomonas aeruginosa colonization and this bacterium is resistant to immune system clearance and drug control. Particularly, the biofilm mode of growth protects several microorganisms from host defenses and antibacterial drugs, mainly due to a delayed penetration of the drug through the biofilm matrix. Biofilm, together with lung mucus viscosity and tenacity, reduces, therefore, the effectiveness of conventional antibiotic therapy in CF. The aim of this research was to design and develop a stable, portable, easy to use dry powder inhaler (DPI) for CF patients, able to release directly to the lung an association of macrolide antibiotics (clarithromycin) and a mucolytic agent (N-Acetyl-Cysteine). Its effectiveness is based on the counteracting of the characteristics of P. aeruginosa infections in CF (lung bacterial adhesion to lung epithelium, biofilm formation and mucus viscosity) and the ability to let the antimicrobial drug exert their pharmacological action. A solution of these two drugs, without any excipients, was spray-dried to obtain respirable microparticles, characterized by aerodynamic diameters suitable for inhalation (

This study reports the development of a one-step method for the production of antimicrobial protective coatings for aluminum surfaces with titania nanoparticles. An aerosol flame synthesis system was used to produce monodisperse, ultra-fine TiO 2 nanoparticles, which were directly deposited by thermophoresis onto plates of aluminum alloy by means of a rotating disc. Fuel-lean reactor conditions were used to synthesize pure anatase nanoparticles of 3.5 nm in diameter. Substrates were mounted onto the rotating disc that repetitively passes through the flame. Convection due to the rotational motion cooled the substrates, on which particles were deposited as films by thermophoresis. Such a system allowed to obtain submicron coatings of different thickness, by varying the total time of deposition. The antimicrobial activity of TiO 2 coatings was tested against the Gram positive bacterium Staphylococcus aureus . To determine the inhibition of biofilms formation, microbes were plated on TiO 2 coatings and a semi-quantitative colorimetric assay was performed using crystal violet. The tests showed that the TiO 2 coating obtained with t des =10 s inhibits up to 70-80% Staphylococcus aureus biofilm formation, and the inhibition of biofilms formation was confirmed by means of Scanning Electron Microscopy observation. Also, the antimicrobial properties of the coatings was enhanced by irradiating the samples in the UV region. The results of the present work are promising for using titania films as protective coatings for applications where an antimicrobial activity is required.

Pharmacological evidences have correlated a low incidence of osteoporosis, breast cancer, cardiovascular disease, and colon cancer in Asian populations, high consumers of soya, to the properties of soy isoflavones, more specifically to daidzein and genistein. However, in spite of the potent biological activity, their poor water solubility has a strong negative effect on bioavailability. In this study, an innovative technique, nano spray drying, was used to obtain nanoparticles loaded with a soybean dry extract while carboxymethyl cellulose was used as the excipient. The optimization of the process conditions allowed for the manufacturing of stable nanoparticles with a mean size of around 650 nm, a narrow size distribution, and a high encapsulation efficiency (between 78 % and 89 %). The presence of carboxymethyl cellulose was able to stabilize the isoflavone extract and enhance its affinity with aqueous media, strongly increasing its permeation through biological membranes up to 4.5-fold higher than pure soy isoflavone extract raw material and twice its homologous minispray-dried formulation. These results are very useful for the administration of the extract, either topically or orally, suggesting that the isoflanones extract nanoparticulate powder obtained by nano spray drying has great potential to enhance extract bioavailability and could be used as an ingredient to be enclosed in dietary supplements and nutraceutical and cosmeceutical products.

Aerogels are an exceptional group of nanoporous materials with outstanding physicochemical properties. Due to their unique physical, chemical, and mechanical properties, aerogels are recognized as promising candidates for diverse applications including, thermal insulation, catalysis, environmental cleaning up, chemical sensors, acoustic transducers, energy storage devices, metal casting molds and water repellant coatings. Here, we have provided a comprehensive overview on the synthesis, processing and drying methods of the mostly investigated types of aerogels used in the biological and biomedical contexts, including silica aerogels, silica-polymer composites, polymeric and biopolymer aerogels. In addition, the very recent challenges on these aerogels with regard to their applicability in biomedical field as well as for personalized medicine applications are considered and explained in detail.

Ketoprofen lysinate (KL) is one of the most widely used non-steroidal anti-inflammatory drugs in the symptomatic treatment of some chronic inflammatory diseases. Compared to ketoprofen, KL shows better pharmacokinetics and tolerability. However, due to its short half-life of 1-2 h, a multiple dose regimen is required for oral administration. Thus, the present work deals with its encapsulation in a hydrogel-based system by prilling in order to prolong its activity.In this paper, we propose alginate and pectin as carriers and release tailoring agent for the development of hydrogel-based beads for KL retarded and sustained release.Beads were produced by a Nisco Encapsulator® using alginate or pectin. Operative variables were optimized to produce beads with desired morphology and size. Solid state properties were analyzed by SEM and DSC. Drug release performance was studied by Pharmacopeia pH-change assay to simulate gastrointestinal environment.Prilling technique was successfully used to encapsulate high soluble drugs as KL in polysaccharides-based hydrogels. Pectin proved to be a proper polymer able to encapsulate ketoprofen lysine salt. Formulation (F8) showed good morphological properties and size, high drug content (15.6%) and encapsulation efficiency (93.5%) and promising drug release profiles. Hosting F8 in an acid-resistant capsule (DRThe platform may be proposed as potentially useful in the oral administration of NSAIDs in chronic inflammatory diseases affected by circadian rhythm.

Conventional hydrogel drying techniques can often induce collapse and shrinkage of the gel nanostructure. In this work, supercritical drying of alginate hydrogel beads is demonstrated to be a very effective process for aerogels production. The process involves solvent exchange followed by supercritical extraction, which prevents the gel from collapsing, while reproducing an aerogel nanostructure that exactly mimics the original hydrogel. Ethanol and acetone were used as water exchange solvents. Using ethanol, the bead spherical shape and nanostructure were most closely maintained when supercritical drying was performed at 150 bar and 38 °C. In addition, the diameter of the dehydrated beads only decreases by 0.6% compared to the hydrated hydrogels. The use of acetone also generated, at almost all the supercritical drying conditions chosen, aerogel with a uniform internal nanostructure, and the lowest shrinkage of 0.3% was obtained operating at 100 bar and 38 °C. A water/ethanol mixture with a ratio of 2:98...

In this study, a novel preparation method for alginate-based aerogels charged with nonsteroidal anti-inflammatory drugs (NSAIDs) was developed using prilling in combi- nation with supercritical fluid technique. Nanoporous carriers were prepared by laminar jet breakup of drug/alginate solutions or suspensions followed by cross-linking in ethanol or aque- ous CaCl2 solutions, water replacement, and supercritical-CO2-assisted drying. A substantial drug loss was observed for highly soluble ketoprofen lysinate, whereas encapsulation efficiency was satisfying for slightly soluble ketoprofen. The tandem technique successfully produced almost spherical aerogels (sphericity coefficient 0.97-0.99) in narrow size distribution with re- duced particle shrinkage and smooth surface (surface roughness 1.10-1.13); the internal porous texture of the parent hydrogels was preserved and appeared as a network of nanopores with diameters around 200nm. Drug release profiles were monitored using a pH change method to evaluate the possible application of the aerogels as fast dissolving NSAIDs formulation. Aque- ous cross-linking led to aerogels encapsulating ketoprofen in the amorphous form and with an enhanced burst effect in simulated gastric fluid (75% in 30min), whereas ethanol cross-linking produced aerogels embedding drug in crystal clusters with slower dissolution rate. The sys- tem appears an interesting potential carrier for the fast delivery of slightly soluble drugs in the upper gastrointestinal tract. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:185-194, 2013

Fadogia ancylantha Hiern. (Rubiaceae), commonly known as “makoni” or “marange”, is a wild perennial shrub growing in the Eastern Highlands area of Zimbabwe. The leaves have been traditionally used by certain African rural communities as a medicine and beverage to boost the immune system, to tone muscles, and strengthen bones and for the treatment of topical ulcers. The plant is also thought to have antipoisonous and aphrodisiac properties. 1 The leaves and stems when fermented and dried are used for producing a black tea with antioxidant effects, 2 which is caffeine-free and particularly rich in proteins, 1 phenolic compounds, 2 and zinc. 1 It is well recognized that zinc is an essential trace element, influencing growth and reproduction and affecting the development of the immune system and integrity of the skin. Nutritional doses of zinc supplements are able to prevent alteration of the immune system and to improve resistance to infection. 3 Cosmetic compositions comprising F. ancylantha extracts are reported to improve skin tone due to antiaging, antibacterial, and anti-free-radical effects on aged, photoaged, stressed, and tired skin, showing simultaneously protective and restorative properties. 4 For centuries, the local population in Zimbabwe has brewed Makoni tea instead of commercial brands, with the tea having grown in popularity and with many commercial products now on the local and global market. Despite its natural nutrients and health benefits, no phytochemical nor biological studies have been reported in the literature on F. ancylantha. However, the related species F. agrestis has been shown to contain monoterpene glycosides, 5 alkaloids, anthraquinones, and flavonoids 6 and to possess aphrodisiac and antiplasmodial activities. 6,7 The present study, carried out on the EtOH-H2O (7:3) extract from a commercial sample of Makoni tea, reports on its triterpenoid saponin and polyphenol composition and its bioactivity. Three new oleanane-type saponins (1-3) were isolated and their structures elucidated using spectroscopic methods including 1D ( 1 H, 13 C, and 1D TOCSY) and 2D NMR (DQF-COSY, ROESY, HSQC, and HMBC) experiments as well as HRESIMS analysis. The in vitro free-radical-scavenging (DPPH test) and antimicrobial (broth microdilution assay) effects of the crude extract and of its major components were also evaluated. Finally, the cytotoxicity of this extract and pure compounds (1-3 and polyphenols) was tested in human umbilical vein endothelial cells (HUVEC) and evaluated as a percentage of apoptotic cells as measured by analysis of hypodiploid nuclei, using a propidium iodide method.

Gastroresistant microparticles for oral administration of hesperidin (Hd) were produced by spray-drying using cellulose acetate phthalate (CAP) as enteric polymer in different polymer/Hd weight ratio (1:1, 3:1, and 5:1), and a series of enhancers of the dissolution rate, such as sodium carboxymethylcellulose crosslinked (CMC), sodium dodecylbenzene sulfonate (SDBS), or Tween85. The raw materials and the microparticles were investigated by differential-scanning calorimetry, X-ray diffraction, infrared spectroscopy and imaged using scanning electron and fluorescence microscopy. In vitro dissolution tests were conducted using a pH-change method to investigate the influence of formulative parameters on the dissolution/release properties of the drug. CAP/Hd microparticles showed a good gastro-resistance but incomplete drug dissolution in the simulated intestinal fluid (SIF). The presence of the enhancers in the formulation produced well-formed microparticles with different size and morphology, containing the drug well coated by the polymer. All the enhancers were able to increase the dissolution rate of Hd in the simulated intestinal environment without altering CAP ability to protect Hd in the acidic fluid. The spray-drying technique and process conditions selected were effective in microencapsulating and stabilizing the flavonoid giving satisfactory encapsulation efficiency, product yield, and microparticles morphology, and a complete drug release in the intestine.