Relationship between gut microbiota and colorectal cancer: Probiotics as a potential strategy for prevention.

Gut microbiota comprise microorganisms residing in the gastrointestinal tract. Some of these microbiota are implicated in the progression of colorectal cancer (CRC). Here, we highlight studies on the effects of meat intake and fermented foods on characteristics of gut microbiota that can influence colitis-associated factors underlying CRC. Gut microbiota can influence the development and progression of CRC, through influencing factors such as secretion of toxins; enzymes for activating carcinogenesis (including ß-glucuronidase, ß-glucosidase, azoreductase, nitroreductase, and alcohol dehydrogenase); hydrogen sulfide generation; generation of reactive oxygen species and inflammation; secondary bile salt transformation; and products of protein fermentation. Additionally, some studies that the composition of gut microbiota (probiotics) or prebiotics plays an important role in the production of short chain fatty acids, inactivation enzymes for carcinogenesis, antioxidant activities, and inhibition of pathogen colonization. In this review, we discuss various explanatory mechanisms of the relationship between the multifactorial role of the gut microbiota and the development of CRC. Moreover, this review provides fundamental information on dietary fermented food and the gut microbiota, which is helpful for healthy people and those with CRC alike.

Study on the reduction of heterocyclic amines by marinated natural materials in pork belly.

This study was conducted to determine the effect of natural ingredient seasoning on the reduction of heterocyclic amine (HCA) production that may occur when pork belly is cooked at a very high temperature for a long time. Pork belly seasoned with natural ingredients, such as natural spices, blackcurrant, and gochujang, was cooked using the most common cooking methods, such as boiling, pan fry, and barbecue. HCAs in pork belly were extracted through solid-phase extraction and analyzed via high-performance liquid chromatography. For short-term toxicity, a mouse model was used to analyze weight, feed intake, organ weight, and length; hematology and serology analysis were also performed. Results revealed that HCAs formed only when heating was performed at a very high temperature for a long time, not under general cooking conditions. Although the toxicity levels were not dangerous, the method showing the relatively highest toxicity among various cooking methods was barbecue, and the natural material with the highest toxicity reduction effect was blackcurrant. Furthermore, seasoning pork belly with natural materials containing a large amount of antioxidants, such as vitamin C, can reduce the production of toxic substances, such as HCAs, even if pork belly is heated to high temperatures.

Main mechanisms for carcinogenic heterocyclic amine reduction in cooked meat by natural materials.

Carcinogens such as heterocyclic amine (HCA), produced during meat cooking, pose a risk of digestive and reproductive cancers in humans. Nevertheless, the exact mechanisms for HCA formation in meat and the control of HCA formation are not known. In this review, we provide an overview of the main cause of HCA formation in cooked meat, fundamental data on natural materials to inhibit HCA carcinogenicity, and methods to analyze HCA in cooked meat. Related past studies has shown that natural substances contain various components that act as antioxidants, and these antioxidants can prevent HCA and mutagenic factors. Free radicals and DNA adducts produced by HCA metabolism have carcinogenic properties. Antioxidants have been found to inhibit oxidative stress caused by free radicals and DNA adducts. Therefore, we can be hypothesized that various natural materials can inhibit HCA carcinogens and mutagens.

The active von Frey filament test: A new technique to evaluate hand tactile sensation in continuous variable units.

The von Frey filament test (vF) is a mainstay of clinical examination. However, its results can be affected by touch speed and other potentially confounding factors. Moreover, the differences between two adjacent filament levels are too large to detect subtle changes. Active vF (AvF) was developed to induce in-depth sensory change. The present study hypothesized that AvF produces different patterns of fingertip sensation; consequently, it could be used as a new assessment tool for neural impairment. The aim of the study was to provide preliminary normative comparative vF and AvF data. This study prospectively examined 32 healthy participants, using AvF and vF. The index and the fifth finger volar pad were examined using AvF and vF, without visual stimulation. The correlation between AvF and vF measurements was evaluated. In addition, differences according to innervation zone, right versus left hand, and gender, and the correlation between AvF values and subjects' age were analyzed. Mean AvF value was significantly higher and had greater variance than vF (111.3 ± 46.9 vs. 24.1 ± 9.8; P < 0.01). The Spearman correlation coefficient between AvF and vF was 0.341. Values were similar in the index and fifth fingers and right and left hands. However, values were significantly different between women and men. The correlation between age and AvF values was 0.259. AvF provided more precise values, with continuous units for tactile sensation, excluding tester-dependent factors. Furthermore, AvF and vF values may not be correlated.

Performance and Cost Analysis of Natural Gas Combined Cycle Plants with Chemical Looping Combustion.

The natural gas combined cycle (NGCC) is the most popular and efficient fossil fuel power plant; however, integrating a carbon capture system reduces its performance efficiency. The demand to reduce the carbon capture cost and improve eco-friendliness drives the development of alternatives. In this study, four alternative NGCC-based process schemes were designed: NGCC with amine carbon capture as a base configuration and NGCCs with three different chemical looping combustion (CLC) configurations. Detailed heat and material balances were evaluated for all four cases using the PRO/II simulation package. A comparative analysis of the gross and net power, plant efficiency, and carbon capture efficiency, which are imperative to optimizing the process configuration, was conducted for all of the proposed cases. All NGCC-CLC processes could produce higher net power than NGCC-MEA because the amine regenerator consumes a high amount of power in its operation. In the condition using an equal amount of natural gas supply, NGCC-CLC configurations using excess air could produce a net power of 510.1 MW with a plant efficiency of 44.35%. The excess air fed in both cases enabled the turbine to generate more power. NGCC-CLC using excess air with steam turbine integration has an investment cost of 132.9 $/net MWh, an operating cost of 56.7 $/net MWh year, and a levelized cost of electricity of 90.9 $/MWh. In addition, NGCC-CLC with excess air resulted in a carbon capture efficiency of 99.93% under 59.2 $/ton of CO2, which was higher than that of NGCC-MEA with a carbon efficiency of 95.1%. NGCC-CLC using excess air with steam turbine integration is considered as the most efficient process scheme for generating power from natural gas with regard to efficiency, cost, and environmental impact.

Synergistic Effect of a Dual-Salt Liquid Electrolyte with a LiNO3 Functional Additive toward Stabilizing Thin-Film Li Metal Electrodes for Li Secondary Batteries.

Li metal thickness has been considered a key factor in determining the electrochemical performance of Li metal anodes. The use of thin Li metal anodes is a prerequisite for increasing the energy density of Li secondary batteries intended for emerging large-scale electrical applications, such as electric vehicles and energy storage systems. To utilize thin (20 µm thick) Li metal anodes in Li metal secondary batteries, we investigated the synergistic effect of a functional additive (Li nitrate, LiNO3) and a dual-salt electrolyte (DSE) system composed of Li bis(fluorosulfonyl)imide (LiTFSI) and Li bis(oxalate)borate (LiBOB). By controlling the amount of LiNO3 in DSE, we found that DSE containing 0.05 M LiNO3 (DSE-0.05 M LiNO3) significantly improved the electrochemical performance of Li metal anodes. DSE-0.05 M LiNO3 increased the cycling performance by 146.3% [under the conditions of a 1C rate (2.0 mA cm-2), DSE alone maintained 80% of the initial discharge capacity up to the 205th cycle, whereas DSE-0.05 M LiNO3 maintained 80% up to the 300th cycle] and increased the rate capability by 128.2% compared with DSE alone [the rate capability of DSE-0.05 M LiNO3 = 50.4 mAh g-1, and DSE = 39.3 mAh g-1 under 7C rate conditions (14.0 mA cm-2)]. After analyzing the Li metal surface using scanning electron microscopy and X-ray photoelectron spectroscopy, we were able to infer that the stabilized solid electrolyte interphase layer formed by the combination of LiNO3 and the dual salt resulted in a uniform Li deposition during repeated Li plating/stripping processes.

Cognitive impairment is associated with elevated serum homocysteine levels among older adults.

PURPOSE: The aim of this study was to examine the associations between the risk of cognitive impairment and the serum levels of folate, vitamin B12, and homocysteine (Hcy). METHODS: Subjects were persons aged 60-79 years who participated in the Yangpyeong Cohort study between 2011 and 2012. Cognitive impairment and normal subjects consisted of 100 pairs of old adults matched by age, sex, and education levels. Cognitive function was evaluated with the Korean version of the Mini-Mental State Examination for Dementia Screening (MMSE-DS). Pearson's partial correlation coefficients and conditional multiple logistic regression analysis were applied to determine the associations between cognitive function and the serum levels of folate, vitamin B12, and Hcy. RESULTS: Compared with the matched normal group, the cognitive impairment group had higher proportions of folate deficiency (< 3 ng/mL) and hyperhomocysteinemia (≥ 15 µmol/L). Serum Hcy concentrations were inversely associated with serum folate (r = - 0.234, p = 0.001) and MMSE-DS score (r = - 0.150, p = 0.037) after adjusting for age, sex, and education. The high Hcy group showed a higher prevalence of cognitive impairment (4th vs. 1st quartile, OR 3.30, 95% CI 1.12-9.72, p for trend = 0.014) after adjusting for exercise. CONCLUSIONS: The present findings suggest a putative protective role of high serum folate and normal Hcy against cognitive impairment among older adults.

Virtual daily living test to screen for mild cognitive impairment using kinematic movement analysis.

Questionnaires or computer-based tests for assessing activities of daily living are well-known approaches to screen for mild cognitive impairment (MCI). However, questionnaires are subjective and computerized tests only collect simple performance data with conventional input devices such as a mouse and keyboard. This study explored the validity and discriminative power of a virtual daily living test as a new diagnostic approach to assess MCI. Twenty-two healthy controls and 20 patients with MCI were recruited. The virtual daily living test presents two complex daily living tasks in an immersive virtual reality environment. The tasks were conducted based on subject body movements and detailed behavioral data (i.e., kinematic measures) were collected. Performance in both the proposed virtual daily living test and conventional neuropsychological tests for patients with MCI was compared to healthy controls. Kinematic measures considered in this study, such as body movement trajectory, time to completion, and speed, classified patients with MCI from healthy controls, F(8, 33) = 5.648, p < 0.001, η2 = 0.578. When both hand and head speed were employed in conjunction with the immediate free-recall test, a conventional neuropsychological test, the discrimination power for screening MCI was significantly improved to 90% sensitivity and 95.5% specificity (cf. the immediate free-recall test alone has 80% sensitivity and 77.3% specificity). Inclusion of the kinematic measures in screening for MCI significantly improved the classification of patients with MCI compared to the healthy control group, Wilks' Lambda = 0.451, p < 0.001.

Predicting Autism Spectrum Disorder Using Blood-based Gene Expression Signatures and Machine Learning.

OBJECTIVE: The aim of this study was to identify a transcriptomic signature that could be used to classify subjects with autism spectrum disorder (ASD) compared to controls on the basis of blood gene expression profiles. The gene expression profiles could ultimately be used as diagnostic biomarkers for ASD. METHODS: We used the published microarray data (GSE26415) from the Gene Expression Omnibus database, which included 21 young adults with ASD and 21 age- and sex-matched unaffected controls. Nineteen differentially expressed probes were identified from a training dataset (n=26, 13 ASD cases and 13 controls) using the limma package in R language (adjusted p value ＜0.05) and were further analyzed in a test dataset (n=16, 8 ASD cases and 8 controls) using machine learning algorithms. RESULTS: Hierarchical cluster analysis showed that subjects with ASD were relatively well-discriminated from controls. Based on the support vector machine and K-nearest neighbors analysis, validation of 19-DE probes with a test dataset resulted in an overall class prediction accuracy of 93.8% as well as a sensitivity and specificity of 100% and 87.5%, respectively. CONCLUSION: The results of our exploratory study suggest that the gene expression profiles identified from the peripheral blood samples of young adults with ASD can be used to identify a biological signature for ASD. Further study using a larger cohort and more homogeneous datasets is required to improve the diagnostic accuracy.

Dietary Patterns Derived by Cluster Analysis are Associated with Cognitive Function among Korean Older Adults.

The objective of this study was to investigate major dietary patterns among older Korean adults through cluster analysis and to determine an association between dietary patterns and cognitive function. This is a cross-sectional study. The data from the Korean Multi-Rural Communities Cohort Study was used. Participants included 765 participants aged 60 years and over. A quantitative food frequency questionnaire with 106 items was used to investigate dietary intake. The Korean version of the MMSE-KC (Mini-Mental Status Examination-Korean version) was used to assess cognitive function. Two major dietary patterns were identified using K-means cluster analysis. The "MFDF" dietary pattern indicated high consumption of Multigrain rice, Fish, Dairy products, Fruits and fruit juices, while the "WNC" dietary pattern referred to higher intakes of White rice, Noodles, and Coffee. Means of the total MMSE-KC and orientation score of the participants in the MFDF dietary pattern were higher than those of the WNC dietary pattern. Compared with the WNC dietary pattern, the MFDF dietary pattern showed a lower risk of cognitive impairment after adjusting for covariates (OR 0.64, 95% CI 0.44-0.94). The MFDF dietary pattern, with high consumption of multigrain rice, fish, dairy products, and fruits may be related to better cognition among Korean older adults.

Supplementation of n-3 Polyunsaturated Fatty Acids for Major Depressive Disorder: A Randomized, Double-Blind, 12-Week, Placebo-Controlled Trial in Korea.

BACKGROUND: Controversy over the efficacy of n-3 polyunsaturated fatty acids (PUFAs) in depression continues to this day. The present study investigated the hypothesis that n-3 PUFA supplementation reduces depressive symptoms in Korean patients with major depressive disorder. METHODS: In a randomized, double-blind, placebo-controlled, 12-week, parallel-group trial, 35 patients with Center for Epidemiological Studies Depression Scale Korean version (CES-D-K) scores ≥25 and depression confirmed by a psychiatrist were assigned to take either 3 capsules of n-3 PUFAs (1,140 mg of EPA + 600 mg of DHA; n = 18) or placebo (olive oil + safflower oil; n = 17). RESULTS: Supplementation with n-3 PUFAs significantly reduced Clinical Global Impression Improvement (CGI-I) scores as compared with intake of placebo using intention-to-treat analysis with last-observation-carried-forward after adjusting for energy, fat, and fish intake. However, the CES-D-K, Hamilton Depression Rating Scale-17, and Clinical Global Impression Scale scores did not significantly differ between the n-3 PUFA and placebo groups. After supplementation with n-3 PUFAs, the erythrocyte levels of n-3 PUFAs were significantly increased, but n-6 PUFA levels were decreased. CONCLUSIONS: n-3 PUFAs demonstrated an advantage over placebo that did not reach clinical significance, although CGI-I score was significantly decreased in the n-3 PUFA group as compared with the placebo group.

Profiling of Proteins Regulated by Venlafaxine during Neural Differentiation of Human Cells.

OBJECTIVE: Antidepressants are known to positively influence several factors in patients with depressive disorders, resulting in increased neurogenesis and subsequent relief of depressive disorders. To study the effects of venlafaxine during neural differentiation at the cellular level, we looked at its effect on protein expression and regulation mechanisms during neural differentiation. METHODS: After exposing NCCIT cell-derived EBs to venlafaxine during differentiation (1 day and 7 days), changes in protein expression were analyzed by 2-DE and MALDI-TOF MS analysis. Gene levels of proteins regulated by venlafaxine were analyzed by real-time RT-PCR. RESULTS: Treatment with venlafaxine decreased expression of prolyl 4-hydroxylase (P4HB), ubiquitin-conjugating enzyme E2K (HIP2) and plastin 3 (T-plastin), and up-regulated expression of growth factor beta-3 (TGF-ß3), dihydropyrimidinase-like 3 (DPYSL3), and pyruvate kinase (PKM) after differentiation for 1 and 7 days. In cells exposed to venlafaxine, the mRNA expression patterns of HIP2 and PKM, which function as negative and positive regulators of differentiation and neuronal survival, respectively, were consistent with the observed changes in protein expression. CONCLUSION: Our findings may contribute to improve understanding of molecular mechanism of venlafaxine.

Dietary patterns and cognitive function in Korean older adults.

PURPOSE: The objectives of this study were to identify major dietary patterns and to investigate the association between dietary patterns and cognitive function in older adults. METHODS: This is a cross-sectional study. The data from the Korean Multi-Rural Communities Cohort Study, which is a part of the Korean Genome Epidemiology Study, were used. There were 806 (340 men and 466 women) subjects aged ≥ 60 years. Usual dietary intake was assessed using a quantitative food frequency questionnaire with 106 food items. Cognitive function was assessed using the Korean version Mini-Mental State Examination (MMSE-KC). We conducted factor analysis using the principal component analysis method to identify the major dietary patterns. The association between major dietary patterns and cognitive function was investigated by logistic regression analysis. RESULTS: Three major dietary patterns were identified and assigned descriptive names based on the food items with high loadings: "prudent" pattern, "bread, egg, and dairy" pattern, and "white rice only" pattern. As the white rice only pattern scores increased, a significant decreasing trend for MMSE-KC scores was observed after adjusting for covariates. The bread, egg, and dairy pattern was inversely related to the risk of cognitive impairment, and the white rice only pattern was positively associated with the risk of cognitive impairment. CONCLUSIONS: This study suggests that specific dietary patterns were significantly associated with cognitive impairment in older adults. In particular, like the white rice only pattern, a rice-centered diet without well-balanced meals may increase the risk of cognitive impairment. However, since our study is a cross-sectional design, the possibility of reverse causality should be considered.

Association between living arrangements and depressive symptoms among older women and men in South Korea.

PURPOSE: We investigated the relationship between different types of living arrangements and depressive symptoms among older Korean women and men. METHODS: Data were obtained from a nationally representative cross-sectional health survey conducted in 2009 in South Korea. A total of 60,305 participants (34,172 women and 26,133 men) aged 60 years and older were included in the analysis. The living arrangements were categorised into six types as follows: (1) living with a spouse only; (2) living with a spouse in an extended family; (3) living with a spouse in a nuclear family; (4) living alone; (5) living without a spouse in an extended family; and (6) living without a spouse in a nuclear family. The Korean version of the Center for Epidemiologic Studies Depression Scale was used as the measurement tool for depressive symptoms. We used multiple regression analysis to estimate the effects of living arrangement on depressive symptoms. RESULTS: A total of 16.8 % of the total study population showed depressive symptoms. Living with a spouse only was the most common type of living arrangement (46.3 %). Women and men living with a spouse only were the least likely to have depressive symptoms. However, living without a spouse in a nuclear family and living alone were most strongly associated with depressive symptoms in women (OR 1.81; 95 % CI 1.64-2.00) and men (OR 2.71; 95 % CI 2.43-3.03), respectively. CONCLUSIONS: The prevalence of depressive symptoms are associated with the living arrangements of elderly Koreans. There are gender differences in these associations, that may stem from the different demands of social roles and relationships in the family.

NCAM140 and pCREB Expression after Tianeptine Treatment of SH-SY5Y Cells.

OBJECTIVE: Antidepressants Modulate Neuronal Plasticity. Tianeptine, An Atypical Antidepressant, Might Be Involved In The Restoration Of Neuronal Plasticity; It Primarily Enhances The Synaptic Reuptake Of Serotonin. Ncam140 Is Involved In Neuronal Development Processes, Synaptogenesis And Synaptic Plasticity. We Investigated The Effect Of Tianeptine On The Expression Of Ncam140 And Its Downstream Signaling Molecule In The Human Neuroblastoma Cell Line Sh-sy5y. METHODS: NCAM protein expression was measured in human neuroblastoma SH-SY5Y cells that were cultivated in serum-free media and treated with 0, 10, or 20 µM tianeptine for 6, 24, or 72 hours. NCAM140 expression in the tianeptine treatment group was confirmed by Western blot, and quantified through measurement of band intensity by absorbance. CREB and pCREB expression was identified after treatment with 20 µM tianeptine for 6, 24, and 72 hours by Western blot. RESULTS: Compared to cells treated for 6 hours, cells treated with 0 or 10 µM tianeptine for 72 hours showed a significant increase in NCAM140 expression and cells treated with 20 µM tianeptine showed a significant increase after 24 and 72 hours. The pCREB level in cells treated with 20 µM tianeptine increased in time-dependent manner. CONCLUSION: Our findings indicated that the tianeptine antidepressant effect may occur by induction of NCAM140 expression and CREB phosphorylation.

Carbamylated erythropoietin promotes neurite outgrowth and neuronal spine formation in association with CBP/p300.

Both erythropoietin (EPO) and carbamylated EPO (cEPO) have been shown to increase the length of neurites and spine density in neurons. However, the molecular mechanism underlying the EPO- and cEPO-induced neuronal differentiation has yet to be investigated. To address this issue, we investigated epigenetic modifications that regulate gene expression in neurons. Neurons treated with EPO or cEPO display an upregulation of E1A-binding protein (p300) and p300-mediated p53 acetylation, possibly increasing the transactivation activity of p53 on growth-associated protein 43 (GAP43). Treatment of cells with cEPO markedly increases spine formation and potentiates p300-mediated transactivation of PSD95, Shank2 and 3 compared to EPO. These results demonstrate that cEPO controls neuronal differentiation via acetylation of transcription factors and subsequent transactivation of target genes. These findings have important medical implications because cEPO is of interest in the development of therapeutic agents against neuropsychiatric disorders.

An association between the reduced levels of SLC1A2 and GAD1 in the dorsolateral prefrontal cortex in major depressive disorder: possible involvement of an attenuated RAF/MEK/ERK signaling pathway.

Previous human postmortem studies have shown that expression of glutamate transporters (SLC1A2 and SLC1A3) and gamma-aminobutyric acid-synthesizing enzyme [glutamic acid decarboxylase 1 (GAD1)] are reduced in the dorsolateral prefrontal cortex (dlPFC) in subjects with major depressive disorder (MDD). However, no studies have explored the association between these two molecules and its related biological processes in MDD because of limited postmortem sample availability. Data sharing using the Stanley neuropathology consortium integrative database (SNCID), a web-based tool that integrates datasets from the same postmortem brain samples, allowed us to reanalyze existing postmortem data efficiently. We found two datasets where the mRNA levels of GAD1 and SLC1A2 in subregions of the dlPFC were significantly and marginally lower in subjects with MDD (n = 15) than in controls (n = 15) (p = 0.045 and 0.057, respectively). In addition, there was a positive correlation between these two molecules (n = 30, p < 0.05). Spearman's rank correlation analysis using all available datasets revealed that the expression levels of both GAD1 and SLC1A2 mRNAs were commonly correlated with the expression levels of several neuropathological markers in the dlPFC in all of the SNCID subjects (n = 60, p < 0.001). Most of these markers are known to be involved in the RAF/MEK/ERK signal transduction pathway. This exploratory study provides an initial step for future studies to investigate an association between the reductions in SLC1A2 and GAD1 mRNA expression and their relation to the attenuation of the RAF/MEK/ERK signaling pathway in the dlPFC in MDD. The integration of the existing archival data may shed light on one important aspect of the pathophysiology of MDD.

Evidence-based, non-pharmacological treatment guideline for depression in Korea.

Although pharmacological treatment constitutes the main therapeutic approach for depression, non-pharmacological treatments (self-care or psychotherapeutic approach) are usually regarded as more essential therapeutic approaches in clinical practice. However, there have been few clinical practice guidelines concerning self-care or psychotherapy in the management of depression. This study introduces the 'Evidence-Based, Non-Pharmacological Treatment Guideline for Depression in Korea.' For the first time, a guideline was developed for non-pharmacological treatments for Korean adults with mild-to-moderate depression. The guideline development process consisted of establishing several key questions related to non-pharmacologic treatments of depression, searching the literature for studies which answer these questions, assessing the evidence level of each selected study, drawing up draft recommendation, and peer review. The Scottish Intercollegiate Guidelines Network grading system was used to evaluate the quality of evidence. As a result of this process, the guideline recommends exercise therapy, bibliotherapy, cognitive behavior therapy, short-term psychodynamic supportive psychotherapy, and interpersonal psychotherapy as the non-pharmacological treatments for adult patients with mild-to-moderate depression in Korea. Hence, it is necessary to develop specific methodologies for several non-pharmacological treatment for Korean adults with depression.

Development of flurbiprofen-loaded nanoparticles with a narrow size distribution using sucrose.

OBJECTIVE: A novel flurbiprofen-loaded nanoemulsion which gave uniform emulsion droplets with a narrow size distribution was previously reported to be prepared using membrane emulsification method. The purpose of this study is to develop a novel flurbiprofen-loaded nanoparticle with a narrow size distribution and improved bioavailability. METHOD: The nanoparticle was prepared by solidifying nanoemulsion using sucrose as a carrier via spray drying method. Its physicochemical properties were investigated using SEM, DSC and PXRD. Furthermore, dissolution and bioavailability in rats were evaluated compared to a flurbiprofen-loaded commercial product. RESULTS: The flurbiprofen-loaded nanoparticles with flurbiprofen/sucrose/surfactant mixture (1/20/2, weight ratio) gave good solidification and no stickiness. They associated with about 70,000-fold improved drug solubility and had a mean size of about 300 nm with a narrow size distribution. Flurbiprofen was present in a changed amorphous state in these nanoparticles. Moreover, the nanoparticles gave significantly shorter Tmax, and higher AUC and Cmax of the drug compared to the commercial product (p < 0.05). In particular, they showed about nine-fold higher AUC of the drug than did the commercial product. CONCLUSION: These flurbiprofen-loaded nanoparticles prepared with sucrose by the membrane emulsification and spray drying method would be a potential candidate for orally delivering poorly water-soluble flurbiprofen with enhanced bioavailability.

Docetaxel-loaded thermosensitive and bioadhesive nanomicelles as a rectal drug delivery system for enhanced chemotherapeutic effect.

PURPOSE: To investigate the potential of thermosensitive and biadhesive nanomicelles in improving the bioavailability of docetaxel (DCT) and its chemotherapeutic effect. METHOD: DCT-loaded nanomicelles were prepared by emulsufication and characterized in terms of physico-chemical and visco-elastic parameters. The optimzed formulation was evaluated for in vivo localization, pharmacokinetic and anti-tumor efficacy. RESULTS: The hydrodynamic size of DCT-loaded nanomicelles was approximately 13 nm and the nanomicelles exhibited a sufficient gelation strength (9250 mPa·s) and bioadhesive force (2100 dyn/cm²) to be retained in the upper part of rectum. We observed a high rectal bioavailability of 29% DCT compared to that following oral administration in rats, as it successfully evaded the multidrug efflux transporters and hepatic first-pass metabolism. Plasma concentration around ∼50 ng/mL was maintained throughout the study period (12 h) while Taxotere® attained subtherapeutic range within 4 h of drug administration. Results also revealed that the rectally administered DCT-loaded nanomicelles exhibited a significant anti-tumor effect (200 mm³) with a reduced toxicity profile when compared to orally administered DCT (950 mm³). Furthermore, histological study showed that the rectal mucosa was completely intact with no signs of irritation upon treatment with DCT-loaded nanomicelles. CONCLUSIONS: Taken together, our novel thermosensitive and biadhesive nanomicelles demonstrated the ability to improve the bioavailability and chemotherapeutic potential of DCT in vivo. To the best of our knowledge, this is the first report describing the rectal delivery of DCT-loaded nanomicelles.