Morphological Changes and Cellular Uptake of Functionalized Graphene Oxide Loaded with Protocatechuic Acid and Folic Acid in Hepatocellular Carcinoma Cancer Cell.

The development of nanocomposites has swiftly changed the horizon of drug delivery systems in defining a new platform. Major understanding of the interaction of nanocomposites with cells and how the interaction influences intracellular uptake is an important aspect to study in order to ensure successful utilisation of the nanocomposites. Studies have suggested that the nanocomposites' ability to permeate into biological cells is attributable to their well-defined physicochemical properties with nanoscale size, which is relevant to the nanoscale components of biology and cellular organelles. The functionalized graphene oxide coated with polyethylene glycol, loaded with protocatechuic acid and folic acid (GOP-PCA-FA) nanocomposite intracellular uptake was analysed using transmission electron microscope. The accumulation of fluorescent-labelled nanocomposites in the HepG2 cell was also analysed using a fluorescent microscope. In vitro cellular uptake showed that there was uptake of the drug from 24 h into the cells and the release study using fluorescently tagged nanocomposite demonstrated that release and accumulation were observed at 24 h and 48 h. Moreover, the migration ability of tumor cells is a key step in tumor progression which was observed 48 h after treatment. The GOP serves as a potential nanocarrier system which is capable of improving the therapeutic efficacy of drugs and biomolecules in medical as well as pharmaceutical applications through the enhanced intracellular release and accumulation of the encapsulated drugs. Nonetheless, it is essential to analyse the translocation of our newly developed GOP-PCA-FA, and its efficiency for drug delivery, effective cellular uptake, and abundant intracellular accumulation would be compromised by possible untoward side effects.

Cyanobacteria and Microalgae as Sources of Functional Foods to Improve Human General and Oral Health.

In the scenario of promising sources of functional foods and preventive drugs, microalgae and cyanobacteria are attracting global attention. In this review, the current and future role of microalgae as natural sources of functional foods for human health and, in particular, for oral health has been reported and discussed in order to provide an overview on the state of art on microalgal effects on human oral health. It is well known that due to their richness in high-valuable products, microalgae offer good anti-inflammatory, antioxidant, antitumoral, anti-glycemic, cholesterol-lowering, and antimicrobial activity. Moreover, the findings of the present research show that microalgae could also have a significant impact on oral health: several studies agree on the potential application of microalgae for oral cancer prevention as well as for the treatment of chronic periodontitis and different oral diseases with microbial origin. Thus, beneficial effects of microalgae could be implemented in different medical fields. Microalgae and cyanobacteria could represent a potential natural alternative to antibiotic, antiviral, or antimycotic therapies, as well as a good supplement for the prevention and co-adjuvant treatment of different oral diseases. Nevertheless, more studies are required to identify strains of interest, increase overall functioning, and make safe, effective products available for the whole population.

Design and Development of Spray-Dried Microsystems to Improve Technological and Functional Properties of Bioactive Compounds from Hazelnut Shells.

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.

MAPLE-based method to obtain biodegradable hybrid polymeric thin films with embedded antitumoral agents.

In this work, antitumor compounds, lactoferrin [recombinant iron-free (Apo-rLf)], cisplatin (Cis) or their combination were embedded within a biodegradable polycaprolactone (PCL) polymer thin film, by a modified approach of a laser-based technique, matrix-assisted pulsed laser evaporation (MAPLE). The structural and morphological properties of the deposited hybrid films were analyzed by Fourier-transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). The in vitro effect on the cells' morphology and proliferation of murine melanoma B16-F10 cells was investigated and correlated with the films' surface chemistry and topography. Biological assays revealed decreased viability and proliferation, lower adherence, and morphological modifications in the case of melanoma cells cultured on both Apo-rLf and Cis thin films. The antitumor effect was enhanced by deposition of Apo-rLf with Cis within the same film. The unique capability of the new approach, based on MAPLE, to embed antitumor active factors within a biodegradable matrix for obtaining novel biodegradable hybrid platform with increased antitumor efficiency has been demonstrated.

Stability of sulforaphane for topical formulation.

CONTEXT: Sulforaphane (SFN) is a natural compound that has been investigated as a chemopreventive agent. SFN has been shown to inhibit the activator-protein-1 (AP-1) transcription factor and may be effective for inhibition of ultraviolet (UV) induced skin carcinogenesis. This study was designed to investigate the stability of SFN as a function of pH, temperature and in various solvents and formulations. MATERIALS AND METHODS: Stability was analyzed using high-performance liquid chromatography. A potential lead formulation was identified and evaluated in vivo. RESULTS: SFN was determined to undergo apparent first-order degradation kinetics for the conditions explored. It was observed that SFN undergoes base catalyzed degradation. Buffer species and solvent type impacts stability as well. SFN was found to be very sensitive to temperature with degradation rate changing by a factor of nearly 3.1 for every 10 °C change in temperature (at pH 4.0). SFN completely degraded after 30 days in a conventional pharmaceutical cream formulation. Improved stability was observed in organic formulation components. Stability studies were conducted on two nonaqueous topical formulations: a polyethylene glycol (PEG) ointment base and an organic oleaginous base. CONCLUSION: Topically applied SFN in the PEG base formulation significantly reduced AP-1 activation after UV stimulation in the skin of a transgenic mouse model, indicating that SFN in this formulation retains efficacy in vivo.

Sulfosalicylate mediates improved vinorelbine loading into LUVs and antineoplastic effects.

Liposomal vinorelbine formulation is desirable, as it might improve the therapeutic activity of vinorelbine. However, because of its lipophilic and membrane-permeable properties, vinorelbine is hard to be formulated into liposomes using conventional drug-loading technologies. To improve vinorelbine retention, ammonium salts of several anionic agents were employed to prepare liposomal vinorelbine formulations. It was found that 5-sulfosalicylate (5ssa) could form stable complexes with vinorelbine and stabilize entrapped vinorelbine. The resultant vesicles had an in vitro release t(1/2) of ~12.49 hours in NH(3)-containing media, which is longer than those of sulfate and phytate vesicles (~0.57 hours). The circulation half-life of vinorelbine after the injection of 5ssa vesicles into normal mice was ~13.01 hours, accounting for ~2-fold increase relative to that of sulfate vesicles. Improved drug retention correlated with enhanced antitumor efficacy. In the RM-1/c57 model, 5ssa vesicles were more efficacious than sulfate vesicles (P < 0.05). In RM-1/BDF1 and Lewis lung cancer/c57 models, antitumor efficacy was also considerably improved after vinorelbine encapsulation into 5ssa vesicles. For instance, in the RM/BDF1 model, liposomal vinorelbine was at least 4-fold more therapeutically active than free vinorelbine. Our results demonstrated that 5ssa could stabilize vinorelbine relative to other anions, resulting in the formulation with improved drug retention and efficacy. Improved vinorelbine retention might be associated with the formation of insoluble precipitate, which could be proved by precipitation study and decreased drug-release rate at a high D/L ratio.

Application of liposome encapsulation technique to improve anti-carcinoma effect of resveratrol.

AIM: The promising anti-tumor effect of resveratrol (RES) has aroused much interest in recent years, but its clinical application was seriously hindered due to its poor solubility in water. The aim of this study was to improve the water solubility of RES by liposome encapsulation technique for effective tumor treatment. METHODS: This study develops two liposomal formulations to solubilize RES by reverse-phase evaporation method with or without poly(ethylene glycol-2000)-grafted distearolyl phosphatidylethanolamine (DSPE-PEG(2000)). The effect of different formulation factors on the encapsulation efficiency (EE) and the particle sizes were investigated. These factors included the mass ratio of drug to soybean phosphatidylcholine (drug/SPC), the mass ratio of cholesterol to soybean phosphatidylcholine (chol/SPC), the volume ratio of water phase/organic phase and the microfluidization process. The drug release studies were performed in various media, simulating the desired application conditions. The cytotoxicity study was carried out by MTT assay on HeLa and Hep G2 cell lines. RESULTS: The RES EE of 95% was obtained when using drug/SPC (1:40 mass ratio), Chol/SPC (1:10 mass ratio), water phase/oil phase (1:2 volume ratio), microfluidization process (entrance pressure 6 kpa, two times of cycle time). The addition of DSPE-PEG(2000) into the formulation showed little effect on the formation and properties of RES liposome. The release of RES was pH-independent. RES liposomes and PEG-modified liposomes performed significant inhibition effects on both cells growth due to the solubilized RES. CONCLUSION: RES can be effectively loaded into liposomes and its anti-cancer effect was evidently improved by the application of liposome encapsulation technique.

Improving the anti-tumor effect of genistein with a biocompatible superparamagnetic drug delivery system.

The practical application of genistein as a low toxicity chemotherapeutic drug is hindered by many of its in vivo properties. To overcome these obstacles, a new multifunctional drug delivery system is developed, which is based on covalently attaching genistein onto Fe3O4 nanoparticles coated by cross-linked carboxymethylated chitosan (CMCH). The structure of the Fe3O4-CMCH-genistein nano-conjugate was confirmed by transmission electron micrographs (TEM), X-ray diffraction (XRD) and Fourier-transfer infrared (FT-IR) spectroscopy. The nano-conjugate shows good water solubility and superparamagnetic properties with a saturation magnetization of 55.1 emu/g. The effects of free genistein and FeO4-CMCH-genistein nano-conjugate on the proliferation and apoptosis of gastric cancer cell line SGC-7901 were investigated by MTT assay and flow cytometry (FACS). MTT results indicate that the Fe3O4-CMCH-genistein nano-conjugate exhibits a significantly enhanced inhibition effect to the SGC-7901 cancer cells than the free genistein. FACS data suggests that the inhibition on cell proliferation of the nano-conjugate is related with an induced apoptosis process. This drug delivery system is promising for future multifunctional chemotherapeutic application that combines drug release and magnetic hyperthermia therapy.

Microencapsulation of amorphous solid dispersions of fenretinide enhances drug solubility and release from PLGA in vitro and in vivo.

The purpose of this study was to develop solid dispersions of fenretinide(4HPR), incorporate them into poly(lactic-co-glycolic)(PLGA) millicylindrical implants, and evaluate the resulting implants in vitro and in vivo for future applications in oral cancer chemoprevention. Due to the extreme hydrophobicity of 4HPR, 4HPR-polyvinylpyrrolidone (PVP) amorphous solid dispersions(ASDs) were prepared for solubility enhancement. The optimal PVP-4HPR ratio of 9/1(w/w) provided a 50-fold solubility enhancement in aqueous media, which was sustained over 1 week. PVP-4HPR ASD particles were loaded into PLGA millicylinders and drug release was evaluated in vitro in PBST and in vivo by recovery from subcutaneous injection in rats. While initial formulations of PLGA PVP-4HPR millicylinders only released 10% 4HPR in vitro after 28 days, addition of the plasticizer triethyl-o-acetyl-citrate(TEAC) into PVP-4HPR ASDs resulted in a 5.6-fold total increase in drug release. Remarkably, the TEAC-PVP-4HPR PLGA implants demonstrated slow, continuous, and nearly complete release over 1 month in vivo compared to a 25% release for our previously reported formulation incorporating solubilizers and pore-forming agents. Hence, a combination of PLGA plasticizer and ASD formation provides an avenue for long-term controlled release in vivo for the exceptionally difficult drug to formulate, 4HPR, and a suitable formulation for future evaluation in rodent models of oral cancer.

Specific Modification with TPGS and Drug Loading of Cyclodextrin Polyrotaxanes and the Enhanced Antitumor Activity Study in Vitro and in Vivo.

A kind of specific cyclodextrin polyrotaxanes (PRs) drug delivery system was developed for an effective drug delivery and enhancing antitumor effect. In this work, we prepared the PR by using α-CD derivatives and dicarboxyl-PEG (Mn = 4200) self-assembling and end-capping with ß-CD derivatives. Then, we chose d-a-Tocopheryl polyethylene glycol 1000 succinate (TPGS) with an antitumor effect to modify the PR. The modified PRs have a certain anticancer effect and can assist the anticancer drug to treat cancer. The 10-hydroxycamptothecin (HCPT) was combined to the specific PRs by covalent bonds to prepare drug-loaded specificity PRs (PR-TPGS-HCPT). The enhanced antitumor activities of PR-TPGS-HCPT were studied by in vitro and in vivo experiments, and the experiment results proved that the TPGS could effectively assist the drug to treat cancer and prolong the lifetime of the tumor-bearing mice. Therefore, this research provides a promising drug-loaded material for the cancer treatment and the specific water-soluble PRs will have potential applications in the biomedical field.

Compatibility of chewing gum excipients with the amino acid L-cysteine and stability of the active substance in directly compressed chewing gum formulation.

Using L-cysteine chewing gum to eliminate carcinogenic acetaldehyde in the mouth during smoking has recently been introduced. Besides its efficacy, optimal properties of the gum include stability of the formulation. However, only a limited number of studies exist on the compatibility of chewing gum excipients and stability of gum formulations. In this study we used the solid-state stability method, Fourier transform infrared spectroscopy and isothermal microcalorimetry to investigate the interactions between L-cysteine (as a free base or as a salt) and excipients commonly used in gum. These excipients include xylitol, sorbitol, magnesium stearate, Pharmagum S, Every T Toco and Smily 2 Toco. The influence of temperature and relative humidity during a three-month storage period on gum formulation was also studied. Cysteine alone was stable at 25 degrees C/60% RH and 45 degrees C/75% RH whether stored in open or closed glass ambers. As a component of binary mixtures, cysteine base remained stable at lower temperature and humidity but the salt form was incompatible with all the studied excipients. The results obtained with the different methods corresponded with each other. At high temperature and humidity, excipient incompatibility with both forms of cysteine was obvious. Such sensitivity to heat and humidity during storage was also seen in studies on gum formulations. It was also found that cysteine is sensitive to high pressure and increase in temperature induced by compression. The results suggest that the final product should be well protected from temperature and humidity and, for example, cooling process before compression should be considered.

Gellan gum macrobeads loaded with naproxen: The impact of various naturally derived polymers on pH-dependent behavior.

Aims After oral administration, naproxen generates several side-effects related to stomach malfunction. Undoubtedly, the enteric dosage forms with naproxen can be considered as safer. Moreover, since it has been evidenced that development and growth of colorectal cancer is related to the presence of cyclooxygenase, naproxen is investigated in terms of the tumor prevention. The aim of the present work was to formulate and evaluate the properties of novel naproxen-loaded macrobeads, made on the basis of low-acyl gellan gum and its blends with carrageenans, guar gum, cellulose sulfate, and dextran sulfates. Method Seven formulations were prepared by ionotropic gelation. The morphology of the dried beads was evaluated by scanning electron microscopy. The next step focused on Raman spectroscopy and thermal analysis of naproxen, polymers, and the beads. Next, the swelling behavior was examined in three acceptor fluids at pH = 1.2; 4.5, and 7.4. The beads were evaluated regarding naproxen content and encapsulation efficiency. The last stage of the work concerned the drug release studies. Results Addition of any other polysaccharide than gellan resulted in flattening of the beads upon drying. Differential scanning calorimetry confirmed the crystalline form of naproxen. Raman spectra showed that no apparent interactions occurred. In the acidic environment, all the beads revealed the tendency to absorb water. The beads swelled to the greatest extent at pH = 4.5. Naproxen was released from the beads at a varied rate. At pH = 7.4, the most prolonged release was observed for the beads containing carrageenans. Conclusions We have proved that blending of gellan with various polysaccharides can change the pH-dependent properties of the beads loaded with naproxen. We believe that the information enclosed in the paper will be of particular importance regarding the development and characteristics of novel oral dosage forms based on natural polymers.

Gallic acid loaded PEO-core/zein-shell nanofibers for chemopreventive action on gallbladder cancer cells.

Coaxial electrospinning was used to develop gallic acid (GA) loaded poly(ethylene oxide)/zein nanofibers in order to improve its chemopreventive action on human gallbladder cancer cells. Using a Plackett-Burman design, the effects of poly(ethylene oxide) and zein concentration and applied voltage on the diameter and morphology index of nanofibers were investigated. Coaxial nanofibers were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). GA loading efficiency as high as 77% was obtained under optimal process conditions. The coaxial nanofibers controlled GA release in acid and neutral pH medium. Cytotoxicity and reactive oxygen species (ROS) production on gallbladder cancer cell lines GB-d1 and NOZ in the presence of GA-nanofibers were assessed. GA-nanofibers triggered an increase in the cellular cytotoxicity compared with free GA on GB-d1 and NOZ cells. Statistically significant differences were found in ROS levels of GA-nanofibers compared with free GA on NOZ cells. Differently, ROS production on GB-d1 cell line was similar. Based on these results, the coaxial nanofibers obtained in this study under optimized operational conditions offer an alternative for the development of a GA release system with improved chemopreventive action on gallbladder cancer cells.

Development of Colorectal-Targeted Dietary Supplement Tablets Containing Natural Purple Rice Bran Oil as a Colorectal Chemopreventive.

Colorectal cancer occurs due to various factors. The important risks are dietary lifestyle and inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis. It has been found that the inhibitory enzyme cyclooxygenase-2 (COX-2) in the colorectal region can potentially reduce the risk of colorectal cancer. The present study investigated rice bran oil from natural purple rice bran, which exhibits antioxidant and anti-inflammatory activity. This study aimed to evaluate the bioactive compound content of natural purple rice bran oil (NPRBO) derived from native Thai purple rice and the anti-inflammatory activity of NPRBO in colorectal cancer cells, and to develop a colorectal delivery platform in the form of film-coated tablets. NPRBO from the rice bran of five different Thai purple rice cultivars, namely Khao’ Gam Leum-Phua (KGLP), Khao’ Gam Boung (KGB), Khao’ Gam Thor (KGT), Khao’ Gam Pah E-Kaw (KGPEK), and Khao’ Niaw Dam (KND), were extracted using the supercritical carbon dioxide extraction technique. The amount of γ-oryzanol (ORY), tocotrienols, and tocopherols present in NPRBOs and the in vitro anti-inflammatory activity of NPRBO were investigated. The highest anti-inflammatory NPRBO was transformed into a dry and free-flowing powder by liquisolid techniques. Then, it was compressed into core tablets and coated with Eudragit®L100 and Eudragit® NE30D. The in vitro release study of the film-coated NPRBO tablets was performed in three-phase simulated gastrointestinal media. The cultivar KGLP was superior to the other samples in terms of the ORY, tocotrienol and tocopherol contents and anti-inflammatory activity. Aerosil® was the most suitable absorbent for transforming NPRBO into a free-flowing powder and was used to prepare the NPRBO core tablets. The in vitro KGLP-NPRBO film-coated tablet release profile showed that no ORY was released at gastric pH while 85% of ORY was released at pH 7.4 after 6 h; this would be expected to occur in the colorectal area. Therefore, this study demonstrates the potential of KGLP-NPRBO to prevent colorectal cancer via a specific colorectal dietary supplement delivery system.

Computer simulations on the pH-sensitive tri-block copolymer containing zwitterionic sulfobetaine as a novel anti-cancer drug carrier.

In this work, dissipative particle dynamics (DPD) simulations were performed to study the self-assembled microstructures and doxorubicin (DOX) loading/release properties of pH-sensitive amphiphilic triblock copolymer: poly(ε-caprolactone)-b-poly(diethylaminoethyl methacrylate)-b-poly(sulfobetaine methacrylate) or poly (ethylene glycol methacrylate) (PCL-PDEA-PSBMA/PEGMA). Our results show that both copolymers can self-assemble into core-shell-corona micelles in aqueous environment. However, the corona structures are quite different for the two copolymer micelles. The shell layers formed by PEGMA have heterogeneous sizes while the shell layers in PCL-PDEA-PSBMA micelles are homogenous. This is mainly attributed to the stronger hydrophilicity of PSBMA than PEGMA. As the mole concentration of copolymer is increased from 10% to 50%, the microstructures formed by PCL-PDEA-PSBMA and DOX remains spherical micelles whereas PCL-PDEA-PEGMA undergoes structural transition from spherical to cylindrical and finally to lamellar micelles. Interestingly, the studied micelles have a pH-responsive drug release property, owing to the protonation of the PDEA block. The drug release process follows a "swelling-demicellization-release" mode. The multi-scale simulations demonstrate an avenue to the optimal design of nanomaterials for drug delivery with desired properties.

Cancer therapeutics with epigallocatechin-3-gallate encapsulated in biopolymeric nanoparticles.

With the recent quantum leap in chemoprevention by dietary products, their use as cancer therapeutics is garnering worldwide attention. The concept of effortlessly fighting this deadly disease by gulping cups of green tea or swallowing green tea extract capsules is appreciated universally. Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, has generated significant interest in controlling carcinogenesis due to its growth-inhibitory efficacy against a variety of cancers by targeting multiple signaling pathways. However, the success of EGCG in preclinical studies is difficult to translate into clinical trials due to issues of low solubility, bioavailability and an uncertain therapeutic window. The laborious and expensive journey of drugs from the laboratory to commercialization can be improved by utilizing nanoparticles as anti-cancer drug carriers. Exploitation of biopolymeric nanoparticles in recent years has improved EGCG's biodistribution, stability and tumor selectivity, revealing its superior chemopreventive effects. This review briefly summarizes recent developments regarding the targets and side effects of EGCG, complications associated with its low bioavailability and critically analyses the application of biopolymeric nanoparticles encapsulating EGCG as a next generation delivery systems.

Enhancing the oral bioavailability of biochanin A by encapsulation in mixed micelles containing Pluronic F127 and Plasdone S630.

Biochanin A (BCA), a natural dietary isoflavone, has been reported to show anticancer activities. However, its low biological availability and poor aqueous solubility limit its usefulness as a chemotherapeutic agent. We developed BCA-loaded micelles with Pluronic F127 and Plasdone S630 (BCA-FS). The optimized, spherical-shaped BCA-FS was obtained at a ratio of 1:1 (F127:S630). The particle size was 25.17±1.2 nm, and the zeta potential was -10.9±0.24 mV. BCA solubility in water increased to 5.0 mg/mL after encapsulation, and the drug-loading efficiency was 5.88%±0.76%. In vitro release experiments showed a delayed release of BCA from the mixed micelles. Furthermore, the BCA absorption permeability across a Caco-2 cell monolayer from the apical side to the basolateral side increased by 54% in BCA-FS. A pharmacokinetics evaluation showed a 2.16-fold increase in the relative oral bioavailability of BCA-FS compared with raw BCA, indicating that the mixed micelles may promote absorption in the gastrointestinal tract. A gastrointestinal safety assay was used to assess the reliability and safety of BCA-FS. On the basis of these findings, we conclude that this simple nanomicelle system could be leveraged to deliver BCA and other hydrophobic drugs.

Targeted nanoparticles encapsulating (-)-epigallocatechin-3-gallate for prostate cancer prevention and therapy.

Earlier we introduced the concept of 'nanochemoprevention' i.e. the use of nanotechnology to improve the outcome of cancer chemoprevention. Here, we extended our work and developed polymeric EGCG-encapsulated nanoparticles (NPs) targeted with small molecular entities, able to bind to prostate specific membrane antigen (PSMA), a transmembrane protein that is overexpressed in prostate cancer (PCa), and evaluated their efficacy in preclinical studies. First, we performed a molecular recognition of DCL- and AG-PEGylation on ligand binding on PSMA active site. Next, the biocompatible polymers PLGA-PEG-A were synthesized and used as base to conjugate DCL or AG to obtain the respective copolymers, needed for the preparation of targeted NPs. The resulting EGCG encapsulating NPs led to an enhanced anti-proliferative activity in PCa cell lines compared to the free EGCG. The behavior of EGCG encapsulated in NPs in modulating apoptosis and cell-cycle, was also determined. Then, in vivo experiments, in mouse xenograft model of prostatic tumor, using EGCG-loaded NPs, with a model of targeted nanosystems, were conducted. The obtained data supported our hypothesis of target-specific enhanced bioavailability and limited unwanted toxicity, thus leading to a significant potential for probable clinical outcome.

Kinetic and thermodynamic studies of sulforaphane adsorption on macroporous resin.

The adsorption equilibrium, kinetic and thermodynamic of sulforaphane (SF) adsorption onto macroporous resin in aqueous phase were studied. The SP850 resin was screened as the appropriate resin for SF purification. From the equilibrium studies, the Redlich-Peterson model was found to be the best for description of the adsorption behavior of SF onto SP850 resin, followed by the Freundlich model and the Langmuir model. Batch equilibrium experiments demonstrated that, in the examined temperature range, the equilibrium adsorption capacity of SP850 resin decreased with increasing adsorption temperature. Thermodynamics studies indicated that the adsorption of SF was a physical, exothermic, and spontaneous process. The adsorption kinetics revealed that the pseudo-second-order kinetic model was suitable to characterize the kinetics of adsorption of SF onto SP850. Finally, the intra-particle diffusion model demonstrated that SF diffused quickly into macropores, and that diffusion slowed down in the meso- and micropores.

Stability of (-)-epigallocatechin gallate and its activity in liquid formulations and delivery systems.

(-)-Epigallocatechin gallate (EGCG) has become a popular disease-preventive supplement worldwide because it may aid in slowing down the onset of age-related diseases such as cancer, diabetes and tissue degeneration. As largely demonstrated in cell culture studies, EGCG possesses antioxidant properties and exhibits favorable effects on gene expression, signal transduction and other cell functions. However, only limited effects have been observed in experimental animals and human epidemiological studies. The inconsistency between the biological activity of EGCG in cell cultures and in vivo can be attributed to its low stability, which not only decreases its bioavailability but also leads to the formation of degradation products and prooxidant molecules with possible side-effects. Understanding EGCG degradation kinetics in solution and in vivo is crucial for its successful clinical application. Ambient conditions (pH, temperature, oxygen) can either enhance or decrease the stability of EGCG, thus influencing its biological activity. Usage of stabilizers and/or encapsulation of EGCG into particulate systems such as nanoparticles or microparticles can significantly increase its stability. In this review, the effects of ambient conditions, stabilizers and encapsulation systems on EGCG stability, activity and degradation rate are illustrated.