Encapsulation of ciprofloxacin within modified xanthan gum- chitosan based hydrogel for drug delivery

The aim of the present work was to investigate the preparation of polyelectrolyte hydrogel as potential drug carrier for antibacterial Ciprofloxacin drug (CFX), intended for controlled release formulation. Hydrogel of N-trimehtyl chitosan (TMC)/sodium carboxymethyl xanthan gum (CMXG) was prepared and ciprofloxacin was employed as a model drug to investigate the loading and release performance of the prepared hydrogel. FTIR, DSC, TGA and SEM analysis were used to characterize the TMC/CMXG hydrogel and its CFX loaded hydrogel. The results showed that the ciprofloxacin was successfully incorporated and released from the prepared hydrogel without the loss of structural integrity or the change in its functionality. The encapsulation efficiency of CFX within the prepared hydrogel was found to be increased with increasing the concentration of drug reaching about 93.8 ± 2.1% with concentration of CFX 250 µg/ml. It was shown also that the drug is entrapped within the gel without significant interaction as confirmed from FTIR spectra and DSC analysis. In vitro release study in phosphate buffer saline (PBS), indicated the steady rise in cumulative drug release with the highest release amount, reaching about 96.1 ± 1.8% up to 150 min, whereby the gel with high drug loading efficiency (3.52 ± 0.07%) displayed faster and higher release rate than that of gel containing a smaller amount of drug (0.44 ± 0.01%). The release kinetics of loaded drug followed zero-order kinetics. CFX drug loaded hydrogel showed high activity against the gram positive and gram negative bacterial strains due to the successful released of CFX from the CFX loaded hydrogel into the tested bacterial strains with the highest diameter of inhibition zone against Escherichia coli (67.0 ± 1.0) as compared to reference antibiotic, Gentamicin (28 ± 0.5). Cytotoxicity of the prepared hydrogel was examined in vitro using lung human normal cell lines and showed the highest cell viability (97 ± 0.5%) at concentration up to 50 µg/ml. Consequently, TMC/CMXG hydrogel can be proposed as new controlled release drug delivery system.     

Encapsulation of Sorbitan Ester-Based Organogels in Alginate Microparticles

Leaching of the internal apolar phase from the biopolymeric microparticles during storage is a great concern as it undoes the beneficial effects of encapsulation. In this paper, a novel formulation was prepared by encapsulating the sunflower oil-based organogels in alginate microparticles. Salicylic acid and metronidazole were used as the model drugs. The microparticles were prepared by double emulsion methodology. Physico-chemical characterization of the microparticles was done by microscopy, FTIR, XRD, and DSC studies. Oil leaching studies, biocompatibility, mucoadhesivity, in vitro drug release, and the antimicrobial efficiency of the microparticles were also performed. The microparticles were found to be spherical in shape. Gelation of the sunflower oil prevented leaching of the internal phase from the microparticles. Release of drugs from the microparticles followed Fickian kinetics and non-Fickian kinetics in gastric and intestinal environments, respectively. Microparticles showed good antimicrobial activity against both Gram-positive (Bacillus subtilis) and Gram-negative (Escherichia coli) bacteria. The results suggested that the developed formulations hold promise to carry oils without leakage of the internal phase. Encapsulation of organogels within the microparticles has improved the drug entrapment efficiency and improved characteristics for controlled delivery applications.

Electronic supplementary material

The online version of this article (doi:10.1208/s12249-014-0147-2) contains supplementary material, which is available to authorized users.KEY WORDS: alginate, drug delivery, leaching, microparticles, organogels     

Alterations in the antibacterial potential of Synechococcus spp. PCC7942 under the influence of UV-B radiations on skin pathogens

Marine organisms are seen as a source of novel drugs and the discovery of new pharmaceutical is increasingly in demand. Cyanobacteria are regarded as a potential target for this as antibacterial, antiviral, antifungal, algicide and cytotoxic activities have been reported in these organisms. They have been identified as a new and rich source of bioactive compounds belonging to diversified groups. Radiation in the UV-B range interferes with various metabolic reactions by generating free radicals and active oxygen species. These deleterious compounds are inactivated by antioxidants. Among them are the carotenoids and phycocyanin which protect against photodynamic action in different ways. Stress plays an important role in the production of bioactive metabolites from organisms. Synechococcus spp. PCC7942 was studied for antibacterial activity against various pathogenic bacteria resistant to a number of available antibiotics after being exposed to UV-B radiation. The antibacterial activity of Synechococcus spp. PCC7942 was studied on five potent skin pathogens. The highest antibacterial activity was seen the methanol extracts of 24 h UV-B exposed cultures of Synechococcus spp. PCC7942. It can be concluded that there was moderate antibacterial activity. Results showed stress, solvent and dose-dependent activity. This antibacterial activity might be due to the enhanced synthesis of carotenoids and phycocyanin under UV-B stress. The purpose of the present study was to relate the inhibitory effects of the cyanobacterial compounds specifically on skin pathogens with exposure to UV-B radiation as UV protecting compounds are already reported in these organisms.     

Injectable biodegradable starch/chitosan delivery system for the sustained release of gentamicin to treat bone infections

Starch-conjugated chitosan microparticles were produced aimed to be used as a carrier for the long term sustained/controlled release of antibiotic drugs to control bone infection. The microparticles were prepared by a reductive alkylation crosslinking method. The obtained microparticles showed a spherical shape, with a slightly rough and porous surface, and a size range of 80-150 μm. Gentamicin was entrapped into the starch-conjugated chitosan microparticles and its release profile was studied in vitro. Increasing concentrations of gentamicin (from 50 to 150 mg/mL) led to a decrease in the encapsulation efficiency (from 67 to 55%), while drug loading increased from 4 to 27%. A sustained release of gentamicin was observed over a period of 30 days. The release kinetics could be controlled using an ionic crosslinker agent. In addition, a bacterial inhibition test on Staphylococcus aureus shows a diameter of the sample inhibition zone ranging from 12 to 17 mm (70-100% of relative activity).     

Preparation and characterization of poly(D,L-lactide-co-glycolide) microspheres for controlled release of human growth hormone

The purpose of this research was to assess the physicochemical properties of a controlled release formulation of recombinant human growth hormone (rHGH) encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) composite microspheres. rHGH was loaded in poly(acryloyl hydroxyethyl) starch (acHES) microparticles, and then the protein-containing microparticles were encapsulated in the PLGA matrix by a solvent extraction/evaporation method. rHGH-loaded PLGA microspheres were also prepared using mannitol without the starch hydrogel microparticle microspheres for comparison. The detection of secondary structure changes in protein was investigated by using a Fourier Transfer Infrared (FTIR) technique. The composite microspheres were spherical in shape (44.6±2.47 μm), and the PLGA-mannitol microspheres were 39.7±2.50 μm. Drug-loading efficiency varied from 93.2% to 104%. The composite microspheres showed higher overall drug release than the PLGA/mannitol microspheres. FTIR analyses indicated good stability and structural integrity of HGH localized in the microspheres. The PLGA-acHES composite microsphere system could be useful for the controlled delivery of protein drugs.     

Solid Lipid Nanoparticles as Delivery Systems for Bioactive Food Components

The inclusion of bioactive compounds, such as carotenoids, omega-3 fatty acids, or phytosterols, is an essential requisite for the production of functional foods designed to improve the long-term health and well-being of consumers worldwide. To incorporate these functional components successfully in a food system, structurally sophisticated encapsulation matrices have to be engineered, which provide maximal physical stability, protect ingredients against chemical degradation, and allow for precise control over the release of encapsulated components during mastication and digestion to maximize adsorption. A novel encapsulation system initially developed in the pharmaceutical industries to deliver lipophilic bioactive compounds is solid lipid nanoparticles (SLN). SLN consist of crystallized nanoemulsions with the dispersed phase being composed of a solid carrier lipid–bioactive ingredient mixture. Contrary to larger colloidal solid lipid particles, specific crystal structures can be “dialed-in” in SLN by using specific surfactant mixtures and ensuring that mean particle sizes are below 100–200 nm. Moreover, in SLN, microphase separations of the bioactive compound from the solidifying lipid matrix can be prevented resulting in an even dispersion of the encapsulated compound in the solid matrix thereby improving chemical and physical stability of the bioactive. In this review article, we will briefly introduce the structure, properties, stability, and manufacturing of solid lipid particles and discuss their emerging use in food science.     

Formulation and in vitro transfection efficiency of poly (D, L-lactideco-glycolide) microspheres containing plasmid DNA for gene delivery

The stability, in vitro release, and in vitro cell transfection efficiency of plasmid DNA (pDNA) poly (D,L.-lactide-co-glycolide) (PLGA) microsphere formulations were investigated. PLGA microspheres containing free and polylysine (PLL)-complexed pDNA were prepared by a water-oil-water solvent extraction/evaporation technique. Encapsulation enhanced the retention of the supereoiled structure of pDNA as determined by gel electrophoresis. PLL complexation of pDNA prior to encapsulation increased both the stability of the supercoiled form and the encapsulation efficiency. Free pDNA was completely degraded after exposure to DNase while encapsulation protected the pDNA from enzymatic degradation. Rapid initial in vitro release of pDNA was obtained from microspheres containing free pDNA. while the release from microspheres containing PLL-complexed pDNA was sustained for more than 42 days. Bioactivity of encapsulated pDNA determined by in vitro cell transfection using Chinese hamster ovary cells (CHO) showed that the bioactivity of encapsulated pDNA was retained in both formulations but to a greater extent with PLL-complexed pDNA microspheres. These results demonstrated that PLGA microspheres could be used to formulate a controlledrelease delivery system for pDNA that can protect the pDNA from DNase degradation without loss of functional activity.     

Swellable Ciprofloxacin-Loaded Nano-in-Micro Hydrogel Particles for Local Lung Drug Delivery

Incorporation of drug-loaded nanoparticles into swellable and respirable microparticles is a promising strategy to avoid rapid clearance from the lung and achieve sustained drug release. In this investigation, a copolymer of polyethylene glycol grafted onto phthaloyl chitosan (PEG-g-PHCs) was synthesized and then self-assembled with ciprofloxacin to form drug-loaded nanoparticles. The nanoparticles and free drug were encapsulated into respirable and swellable alginate micro hydrogel particles and assessed as a novel system for sustained pulmonary drug delivery. Particle size, morphology, dynamic swelling profile, and in vitro drug release were investigated. Results showed that drug-loaded nanoparticles with size of 218 nm were entrapped into 3.9-μm micro hydrogel particles. The dry nano-in-micro hydrogel particles exhibited a rapid initial swelling within 2 min and showed sustained drug release. Preliminary in vivo pharmacokinetic studies were performed with formulations delivered to rats by intratracheal insufflation. Ciprofloxacin concentrations in plasma and in lung tissue and lavage were measured up to 7 h. The swellable particles showed lower ciprofloxacin levels in plasma than the controlled group (a mixture of lactose with micronized ciprofloxacin), while swellable particles achieved higher concentrations in lung tissue and lavage, indicating the swellable particles could be used for controlling drug release and prolonging lung drug concentrations.KEY WORDS: alveolar macrophage, antibiotics, cross-linking, hydrogel swelling, intratracheal insufflation     

Biodegradation of xanthan by salt-tolerant aerobic microorganisms

Summary Three salt-tolerant bacteria which degraded xanthan were isolated from various water and soil samples collected from New Jersey, Illinois, and Louisiana. The mixed culture, HD1, contained aBacillus sp. which produced an inducible enzyme(s) having the highest extracellular xanthan-degrading activity found. Xanthan alone induced the observed xanthan-degrading activity. The optimum pH and temperature for cell growth were 5–7 and 30–35°C, respectively. The optimum temperature for activity of the xanthan-degrading enzyme(s) was 35–45°C, slightly higher than the optimum growth temperature. With a cell-free enzyme preparation, the optimum pH for the reduction of solution viscosity and for the release of reducing sugar groups were different (5 and 6, respectively), suggesting the involvement of more than one enzyme for these two reactions. Products of enzymatic xanthan degradation were identified as glucose, glucuronic acid, mannose, pyruvated mannose, acetylated mannose and unidentified oligo- and polysaccharides. The weight average molecular weight of xanthan samples shifted from 6.5·10⁶ down to 6.0·10⁴ during 18 h of incubation with the cell-free crude enzymes. The activity of the xanthan-degrading enzyme(s) was not influenced by the presence or absence of air or by the presence of Na₂S₂O₄ and low levels of biocides such as formaldehyde (25 ppm) and 2,2-dibromo-3-nitrilopropionamide (10 ppm). Formaldehyde at 50 ppm effectively inhibited growth of the xanthan degraders.     

Stability of Poly(ε-caprolactone) Microparticles Containing Brucella ovis Antigens as a Vaccine Delivery System Against Brucellosis

In previous works, our research group has successfully proved the use of subcellular vaccines based on poly(ε-caprolactone) (PEC) microparticles containing an antigenic extract of Brucella ovis (HS) against experimental brucellosis in both mice and rams. However, the successful exploitation of pharmaceutical products, and therefore of this product as veterinary vaccine, requires preservation of both biological activity and native structure in all steps of development from purification to storage. In this context, we have carried out an accelerated stability study to evaluate the relative stability of HS when loading in PEC microparticles. For this purpose, freeze-dried microparticles were stored at 40 ± 1°C and 75% RH as a preliminary analysis of a stability testing. The results showed that both physico-chemical (size, morphology, antigen content, release profile) and biological (integrity and antigenicity of the HS) properties were preserved after 6 months of storage. On the contrary, after 1 year of storage, the HS release profile was dramatically affected probably due to a progressive loss of the polymer microstructure. In addition, the degradation and loss of the antigenicity of the HS components was also evident by SDS-PAGE and immunoblotting analysis. In fact, after 12 months of storage, only the integrity and antigenicity of two of the major protective proteins of the HS antigenic complex were preserved.     

Morphology and Release Profiles of Biodegradable Microparticles Containing Rhamnolipid Biosurfactant

In an effort to expand the technology of bioremediation of hydrophobic organic compounds, microencapsulation technology was investigated as a method of biosurfactant delivery to contaminated sites. Microparticles are composed of active or inactive materials encapsulated in a polymer coating designed for controlled release of the encapsulated substance. Surface morphology and release profiles of microparticles containing rhamnolipid biosurfactant were investigated for development of a controlled release bioremediation scheme. The evaluation was conducted under laboratory conditions with 45 mg/ml concentration of biosurfactant and a representative environmental medium; using artificial salt water (35 ppt) and deionized water medium as a control. The microparticles were prepared by the water–in–oil–in–water double emulsion solvent evaporation method. The surface morphology was examined after initial preparation, at 0, 15 and 31 days incubation, using light microscopy. Light microscopic images revealed smooth, spherical microparticles that degraded over time in the media. Results indicated that microparticle degradation occurred mostly in the salt water environment, suggesting that the presence of salts (Na⁺ and Cl^? ions) in the water enhanced microparticle degradation. The deionized water environment achieved polymeric degradation that was similar to what was generally reported in the literature. Biosurfactant release was evaluated for polymer molecular weights (M_w) 40, 80, and 200 kDa, in salt water and deionized water media, each of which showed a high initial burst release of biosurfactant, followed by pulse releases that occurred over the 31 day period. The highest level of biosurfactant release of all the molecular weights tested occurred in the M_w 80 kDa. The release from M_w 40 kDa and M_w 200 kDa was not significantly different (P > 0.05). The results showed that this technology may be useful for enhancing bioremediation of residual hydrophobic organic contaminants (HOC) in estuarine and marine environments.     

Immobilization of maltogenase onto polyurethane microparticles from poly(vinyl alcohol) and hexamethylene diisocyanate

A series of porous polyurethane (PU) microparticles from poly(vinyl alcohol) (PVA) and hexamethylene diisocyanate (HMDI) using different ratios of components were obtained by one step method. Molar compositions of PU microparticles were estimated by determination of nitrogen, isocyanate and hydroxyl groups. PU carriers which were synthesized using optimal initial molar ratios of PVA and HMDI were applied for immobilization of maltogenase (MG) from Bacillus stearothermophilus. Immobilized enzyme exhibited higher catalytic activity and enhanced temperature stability in comparison with the native MG. Maximal loading 7.78 mg/g wet carrier was reached when PU microparticles with initial molar ratio of PVA and HMDI = 1:3 was used as a carrier for immobilization. The high efficiency of immobilization (EI) was obtained using PU microparticles when initial molar ratio of HMDI and PVA was 1:1–1:10. High stability of MG immobilized onto PU microparticles during storage was demonstrated. Immobilized starch hydrolyzing enzyme was successfully tested in batch and column type reactors for hydrolysis of potato starch. MG immobilized onto PU enables easy separation from the reaction medium and reuse of the immobilized preparation over seven reaction cycles in bath operation and at least three cycles in column type reactor.     

A Pyruvated Mannose-Specific Xanthan Lyase Involved in Xanthan Degradation by Paenibacillus alginolyticus XL-1

The xanthan-degrading bacterium Paenibacillus alginolyticus XL-1, isolated from soil, degrades approximately 28% of the xanthan molecule and appears to leave the backbone intact. Several xanthan-degrading enzymes were excreted during growth on xanthan, including xanthan lyase. Xanthan lyase production was induced by xanthan and inhibited by glucose and low-molecular-weight enzymatic degradation products from xanthan. A xanthan lyase with a molecular mass of 85 kDa and a pI of 7.9 was purified and characterized. The enzyme is specific for pyruvated mannosyl side chain residues and optimally active at pH 6.0 and 55°C.     

Characterization and Antilisterial Effect of Phosphatidylcholine Nanovesicles Containing the Antimicrobial Peptide Pediocin

Encapsulation may provide increased stability and antimicrobial efficiency to bacteriocins. In this work, the antilisterial peptide pediocin was encapsulated in nanovesicles prepared from partially purified soybean phosphatidylcholine. The maintenance of antimicrobial activity and properties of free and encapsulated pediocin was observed during 13 days at 4 °C, and after this period, the encapsulated pediocin retained 50 % its initial activity. The maintenance of the bioactive properties of free and encapsulated pediocin was observed against different species of Listeria, inhibiting Listeria monocytogenes, Listeria innocua and Listeria ivanovii. The size of vesicles containing pediocin was determined by dynamic light scattering as an average of 190 nm, with little change throughout the observation period. Polydispersity index values were around 0.201 and are considered satisfactory, indicating an adequate size distribution of liposomes. The efficiency of encapsulation was 80 %. Considering these results, the protocol used was appropriate for the encapsulation of this bacteriocin. Results demonstrate the production of stable nanoparticulate material. The maintenance of the properties of pediocin encapsulated in liposomes is fundamental to prospect the stability in different conditions of the food matrix.     

Agglomerates Containing Pantoprazole Microparticles: Modulating the Drug Release

Pantoprazole-loaded microparticles were prepared using a blend of Eudragit® S100 and Methocel® F4M. The accelerated stability was carried out during 6 months at 40°C and 75% relative humidity. In order to improve technological characteristics of the pantoprazole-loaded microparticles, soft agglomerates were prepared viewing an oral delayed release and gastro-resistant solid dosage form. The agglomeration was performed by mixing the pantoprazole microparticles with spray-dried mannitol/lecithin powders. The effects of factors such as the amount of lecithin in the spray-dried mannitol/lecithin powders and the ratio between pantoprazole microparticles and spray-dried mannitol/lecithin powders were evaluated. The pantoprazole-loaded microparticles present no significant degradation in 6 months. The agglomerates presented spherical shape, with smooth surface and very small quantity of non-agglomerated particles. The agglomerates presented different yields (35.5–79.0%), drug loading (58–101%), and mechanical properties (tensile strength varied from 44 to 69 mN mm⁻²), when the spray-dried mannitol/lecithin powders with different lecithin amounts were used. The biopharmaceutical characteristics of pantoprazole microparticles, i.e., their delayed-release properties, were not affected by the agglomeration process. The gastro-resistance of the agglomerates was affected by the amount of spray-dried mannitol/lecithin powders. The ratio of lecithin in the spray-dried mannitol/lecithin powders was the key factor in the agglomerate formation and in the drug release profiles. The agglomerates presenting better mechanical and biopharmaceutical characteristics were prepared with 1:2 (w/w) ratio of pantoprazole-loaded microparticles and mannitol/lecithin (80:20) powder.Key words: agglomerates, delayed release, gastro-resistance, microparticles     

Laccase production and wood degradation by a white-rot fungus Daedalea flavida

A comparative study has been conducted on seven white rot fungi to investigate their abilities to produce laccase and selectively degrade lignin. Laccase was produced constitutively on the different media tested. Of the different lignins, phenolic compounds and sugars involved, the highest laccase yield was obtained on indulin AT. Salicylic acid inhibited enzyme activity. A temperature of 20°C and 0.2% of indulin AT were found to be optimum for enzyme activity. No correlation was found between the amount of enzyme and fungal mass produced. During semisolid degradation of angiospermic wood sawdust, Daedalea flavida caused a total weight loss of 11%, with a lignin loss of 15.77% during two months of decay. Lignin removal was comparatively selective during the first month, during which time laccase production was also higher, indicating its probable role in lignin degradation.     

Polymeric Nanoparticles as Oral Delivery Systems for Encapsulation and Release of Polyphenolic Compounds: Impact on Quercetin Antioxidant Activity & Bioaccessibility

A delivery system containing polymeric (Eudragit) nanoparticles has been developed for encapsulation and controlled release of bioactive flavonoids (quercetin). Nanoparticles were fabricated using a solvent displacement method. Particle size, morphology, and charge were measured by light scattering, electron microscopy and ??-potential. Encapsulation efficiency (EE) and release profiles were determined using electrochemical methods. Molecular interactions within the particle matrix were characterized by X-ray diffraction, differential scanning calorimetry, and infrared spectroscopy. Antioxidant properties of free and encapsulated quercetin were analyzed by TBARS and fluorescence spectroscopy. Bioaccessibility of quercetin was evaluated using an in vitro digestion model. Relatively small (d????370?nm) anionic polymeric nanoparticles were formed containing quercetin in a non-crystalline form (EE????67?%). The main interaction between quercetin and Eudragit was hydrogen bonding. Encapsulated quercetin remained stable during 6?months storage and maintained its antioxidant activity. Quercetin bioaccessibility within simulated small intestinal conditions was improved by encapsulation. The knowledge obtained from this study will facilitate the rational design and fabrication of polymeric nanoparticles as oral delivery systems for encapsulation, protection, and release of bioactive compounds.     

Galactomannan (from Gleditsia sinensis Lam.) and xanthan gum matrix tablets for controlled delivery of theophylline: In vitro drug release and swelling behavior

Galactomannan (G) from Gleditsia sinensis Lam. and xanthan gum (X), as sustained release materials for controlled delivery of theophylline, were mixed in different ratios of 7:3, 5:5, and 3:7 to yield enhanced release-controlling performance. The polysaccharides content of tablets was 10% (w/w), either alone or in mixtures. From in vitro dissolution test, G10% and X10% matrices released 91.4 and 87.7% of drug within 24 h, respectively. The synergistic interactions between galactomannan and xanthan effectively retarded the drug diffusion, and the most sustained drug release (75.5% at 24 h) was found in formulation GX7:3. The drug release data fitted to the kinetic model indicated the anomalous transport mechanism (0.5 < n < 1.0). Additionally, the swelling behavior and morphological changes of the tablets were investigated. The results illustrated the potential of binary mixtures of G. sinensis galactomannan and xanthan as novel sustained release materials for controlled drug delivery.     

Development of Hydrophobized Alginate Hydrogels for the Vessel-Simulating Flow-Through Cell and Their Usage for Biorelevant Drug-Eluting Stent Testing

The vessel-simulating flow-through cell (vFTC) has been used to examine release and distribution from drug-eluting stents in an in vitro model adapted to the stent placement in vivo. The aim of this study was to examine the effect of the admixture of different hydrophobic additives to the vessel wall simulating hydrogel compartment on release and distribution from model substance-coated stents. Four alginate-based gel formulations containing reversed-phase column microparticles LiChroprep® RP-18 or medium-chain triglycerides in form of preprocessed oil-in-water emulsions Lipofundin® MCT in different concentrations were successfully developed. Alginate and modified gels were characterized regarding the distribution coefficient for the fluorescent model substances, fluorescein and triamterene, and release as well as distribution of model substances from coated stents were investigated in the vFTC. Distribution coefficients for the hydrophobic model substance triamterene and the hydrophobized gel formulations were up to four times higher than for the reference gel. However, comparison of the obtained release profiles yielded no major differences in dissolution and distribution behavior for both fluorescent model substances (fluorescein, triamterene). Comparison of the test results with mathematically modeled data acquired using finite element methods demonstrated a good agreement between modeled data and experimental results indicating that gel hydrophobicity will only influence release in cases of fast releasing stent coatings.     

Anti-inflammatory activity of benzophenone and xanthone derivatives isolated from Garcinia (Clusiaceae) species

Species of the genus Garcinia have been the source of many benzophenone and xanthone derivatives. Recent data regarding potent biological properties of natural compounds in Garcinia species led us to investigate the in vitro anti-inflammatory effect of three known xanthones, lichexanthone (1), 1,3,6,7-tetrahydroxyxanthone (2), 1,3,5,6-tetrahydroxyxanthone (3), two new xanthones 1-hydroxy-3,6,7-tri-O,O,O-triprenylxanthone (4), 1,6-dihydroxy-3,7-di-O,O-diprenylxanthone (5) and two benzophenones isoxanthochymol (6), guttiferone E (7), isolated from Garcinia nobilis and Garcinia punctata. The Griess assay was used for the measurement of nitric oxide (NO) production in RAW264.7 macrophages and the ferrous oxidation-xylenol orange assay was used to determine the 15-lipoxygenase (15-LOX) inhibitory activity. All the compounds had inhibitory effect on 15-LOX activity to different extents. Compound (7) had the highest anti-LOX activity with an IC₅₀ value of 43.05 μg/mL. At the highest studied concentration (25 μg/mL), compound (4) had the most potent inhibitory activity against NO release with a% of inhibition of 95.42% and less cytotoxic effect on RAW264.7 cells (% of cell viability of 81.40).The results presented here suggest that 1,3,5,6-tetrahydroxyxanthone (3) and guttiferone E (7) are promising inhibitors of NO production and 15-LOX activity. Further studies should be considered in order to elucidate the mechanism by which these compounds exert their inhibitory activities.