Pre-mixing of omega-3 fatty acid-containing liposomes enhances the drug release rate and therapeutic efficacy of anticancer drugs loaded in liposomes.

The therapeutic efficacy of anticancer drugs loaded in liposomes composed of rigid phosphatidylcholine (PC) is hindered by the limited release of these drugs at the tumor site, which in turn hampers delivery of the drug to its intracellular target. In an attempt to improve the therapeutic efficacy of liposomal anticancer drugs, we here explored the use of empty liposomes as "trigger" vehicles to induce drug release from drug-loaded liposomes through liposome-liposome interactions. Empty liposomes containing PC in which omega-3 fatty acids comprised both fatty acid strands (Omega-L) showed a triggering effect on drug release from doxorubicin (DOX)-loaded liposomes (Caelyx). The effectiveness of this triggered-release effect was dependent on the Omega-L composition as well as the mixing ratio of Omega-L to Caelyx. Cryo-TEM and differential calorimetry studies revealed that the Omega-L effect was associated with liposome-liposome interactions that led to loosened membrane packing and increased fluidity of Caelyx. In cultured cells, the intracellular/intranuclear DOX uptake and anticancer efficacy of Caelyx was greatly improved by Omega-L pre-mixing. Intravenous injection of rats with Caelyx, premixed with Omega-L, decreased the area under the plasma concentration-time curve from time zero to time infinity and increased clearance without significantly changing the mean residence time or terminal half-life of DOX compared with Caelyx alone. Ex vivo bioimaging showed that DOX fluorescence in tumors, but not in other organs, was significantly increased by Omega-L premixing. In the mouse xenograft model, premixing of Omega-L with Caelyx suppressed tumor growth 2.5-fold compared with Caelyx. Collectively, the data provide preliminary evidence that the Omega-L-triggered drug release that occurs before and after dosing, particularly at tumor site, improved the therapeutic efficacy of Caelyx. The simple approach described here could enhance the therapeutic value of Caelyx and other anticancer drug-loaded liposomes.

Impact of carrier hydrophilicity on solid self nano-emulsifying drug delivery system and self nano-emulsifying granule system.

The purpose of this study was to investigate the impact of carrier hydrophilicity on solid self nano-emulsifying drug delivery system (SNEDDS) and self nano-emulsifying granule system (SEGS). The mesoporous calcium silicate (Ca-silicate) and hydroxypropyl-ß-cyclodextrin (HP-ß-CD) were utilised as hydrophobic carrier and hydrophilic carrier, respectively. The liquid SNEDDS formulation, composed of Tween80/Kollipohr EL/corn oil (35/50/15%) with 31% (w/w) dexibuprofen, was spray-dried and fluid-bed granulated together with Avicel using Ca-silicate or HP- ß-CD as a solid carrier, producing four different solid SNEDDS and SEGS formulations. Unlike the Ca-silicate-based systems, spherical shape and aggregated particles were shown in HP-ß-CD-based solid SNEDDS and SEGS, respectively. Molecular interaction was detected between Ca-silicate and the drug; though, none was shown between HP-ß-CD and the drug. Each system prepared with either carrier gave no significant differences in micromeritic properties, crystallinity, droplet morphology, size, dissolution and oral bioavailability in rats. However, the HP-ß-CD-based system more significantly improved the drug solubility than did the Ca-silicate-based system. Therefore, both carriers hardly affected the properties of both solid SNEDDS and SEGS; though, there were differences in the aspect of appearance, molecular interaction and solubility.

Aminoclay Nanoparticles Induce Anti-Inflammatory Dendritic Cells to Attenuate LPS-Elicited Pro-Inflammatory Immune Responses.

Although 3-aminopropyl functionalized magnesium phyllosilicate nanoparticles (hereafter aminoclay nanoparticles, ACNs) are well-known nanomaterials employed as drug carriers, their effects on immune cells remain unclear. To address this issue, we explored murine dendritic cells (DCs) as these cells belong to the innate arm of the immune system and function as antigen-presenting cells to elicit adaptive immune responses. We examined the in vitro effects of ACNs on DCs isolated from B6 mice. ACN treatment significantly down-regulated the expression of inflammasome-related markers, including NLRP3, caspase-1, and IL1ß. The ACNs-induced anti-inflammatory DC phenotype was further confirmed by down-regulation of the AKT/mTOR/HIF1α signaling pathway. Such anti-inflammatory effects of ACNs on DCs occurred independently of DC subtypes. To document the effects of ACNs on DCs more clearly, we examined their anti-inflammatory effects on lipopolysaccharide (LPS)-activated DCs. As expected, excessive inflammatory responses (increased mitochondrial ROS and Th1-type cytokines such as IL12 and IL1ß) of LPS-activated DCs were dramatically attenuated by ACN treatment. Furthermore, ACNs down-regulated IFNγ production by antigen-specific CD4+ T cells, which is consistent with a reduced inflammatory phenotype of DCs. Overall, our results provide support for employing ACNs as drug delivery materials with therapeutic potential to control inflammatory disorders.

Hydroxypropyl-ß-cyclodextrin-based solid dispersed granules: A prospective alternative to conventional solid dispersion.

The purpose of the present study was to develop hydroxypropyl-ß-cyclodextrin (HP-ß-CD)-based solid dispersed granules as a superior system to solid dispersion. The solid dispersed granules and solid dispersion were compared in terms of powder property improvement, solubility increment and oral bioavailability enhancement of poorly water-soluble dexibuprofen. Solid dispersion (drug/HP-ß-CD/Tween80 = 1:7:0.1, weight ratio) and solid dispersed granules (drug/HP-ß-CD/Tween80/Microcrystalline cellulose = 1:7:0.1:4) were fabricated using a spray-dryer and fluid bed granulator, respectively. The HP-ß-CD-based solid dispersed granules significantly improved solubility, dissolution profile and oral bioavailability of dexibuprofen compared to pure drug powder. Moreover, the solid dispersed granules maximised the oral bioavailability of dexibuprofen to the same extent as the solid dispersion. However, considerable improvements of powder and tablet properties were observed in solid dispersed granules as compared with solid dispersion. Therefore, HP-ß-CD-based solid dispersed granules would be a prospective alternative to solid dispersion.

Comparison of Three Different Aqueous Microenvironments for Enhancing Oral Bioavailability of Sildenafil: Solid Self-Nanoemulsifying Drug Delivery System, Amorphous Microspheres and Crystalline Microspheres.

BACKGROUND: The purpose of this study was to screen various drug delivery systems for improving the aqueous solubility and oral bioavailability of sildenafil. Three representative techniques, solid self-nanoemulsifying drug delivery systems (SNEDDS), amorphous microspheres and crystalline microspheres, were compared. METHODS: Both microspheres systems contained sildenafil:Labrasol:PVP at a weight ratio of 1:1:6. The amorphous microspheres were manufactured using ethanol, while crystalline microspheres were generated using distilled water. Liquid SNEDDS was composed of sildenafil:Labrasol:Transcutol HP:Captex 300 in the ratio of 1:70:15:15 (w:w:w:w). The solidification process in SNEDDS was performed using HDK N20 Pharma as a solid carrier. RESULTS: The amorphous microspheres appeared spherical with significantly decreased particle size compared to the drug powder. The crystalline microspheres exhibited a rough surface with no major particle-size difference compared with sildenafil powder, indicating that the hydrophilic excipients adhered to the sildenafil crystal. Solid SNEDDS presented a smooth surface, assuming that the oily liquid was adsorbed to the porous solid carrier. According to the physicochemical evaluation, the crystalline state maintained in crystalline microspheres, whereas the crystal state changed to amorphous state in other formulations. Amorphous microspheres, crystalline microspheres and solid SNEDDS produced about 79, 55, 82-fold increased solubility, compared to drug powder. Moreover, the prepared formulations provided a higher dissolution rate (%) and plasma concentration than did the drug powder (performance order; solid SNEDDS ≥ amorphous microspheres ≥ crystalline microspheres > drug powder). Among the formulations, solid SNEDDS demonstrated the highest improvement in oral bioavailability (AUC; 1508.78 ± 343.95 h·ng/mL). CONCLUSION: Therefore, solid SNEDDS could be recommended as an oral dosage form for enhancing the oral bioavailability of sildenafil.

New potential application of hydroxypropyl-ß-cyclodextrin in solid self-nanoemulsifying drug delivery system and solid dispersion.

The purpose of this study was to use hydroxypropyl-ß-cyclodextrin (HP-ß-CD) as a novel carrier in solid SNEDDS and solid dispersions to enhance the solubility and oral bioavailability of poorly water-soluble dexibuprofen. The novel dexibuprofen-loaded solid SNEDDS was composed of dexibuprofen, corn oil, polysorbate 80, Cremophor® EL, and HP-ß-CD at a weight ratio of 45/35/50/15/100. This solid SNEDDS spontaneously formed a nano-emulsion with a size of approximately 120 nm. Unlike the conventional solid SNEDDS prepared with colloidal silica as a carrier, this dexibuprofen-loaded solid SNEDDS exhibited a spherical structure. Similar to the dexibuprofen-loaded solid dispersion prepared with HP-ß-CD, the transformation of the crystalline drug to an amorphous state with no molecular interactions were observed in the solid SNEDDS. Compared to the solid dispersion and dexibuprofen powder, solid SNEDDS significantly enhanced drug solubility and AUC. Therefore, HP-ß-CD is a novel potential carrier in SNEDDS for improving the oral bioavailability of dexibuprofen.

The Effect of a TLR4 Agonist/Cationic Liposome Adjuvant on Varicella-Zoster Virus Glycoprotein E Vaccine Efficacy: Antigen Presentation, Uptake, and Delivery to Lymph Nodes.

Adjuvant CIA09, composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)-based cationic liposomes and the toll-like receptor 4 agonist de-O-acylated lipooligosaccharide (dLOS), has been shown to enhance antibody and cellular immune responses to varicella-zoster virus (VZV) glycoprotein E (gE), recombinant tuberculosis vaccine antigen, and inactivated Japanese encephalitis vaccine. In this study, we investigated its modes of action using VZV gE as a model antigen. Liposomes adsorbed gE and cooperatively with dLOS promoted endocytosis-mediated cellular uptake of gE by mouse dendritic cells in vitro. CIA09 increased the stability and cellular uptake of the antigen at the muscle site of injection, and induced immune cell recruitment and cytokine and chemokine production, which led to efficient antigen delivery to draining lymph nodes. Mouse bone marrow-derived dendritic cells, pulsed with CIA09-adjuvanted gE, efficiently presented gE to antigen-specific T cells, inducing Th1-type biased immunity, as shown by high IFN-γ production. The data indicate that liposomes and dLOS cooperate in the adjuvant activity of CIA09 by promoting antigen uptake and delivery to lymph nodes as well as antigen presentation to T cells.

Enhanced Stability of Indocyanine Green by Encapsulation in Zein-Phosphatidylcholine Hybrid Nanoparticles for Use in the Phototherapy of Cancer.

Indocyanine green (ICG) is a clinically approved near-infrared dye that has shown promise as a photosensitizer for the phototherapy of cancer. However, its chemical instability in an aqueous solution has limited its clinical application. Encapsulating ICG in liposomes, phosphatidylcholine nanoparticles (PC-NP), has shown partial effectiveness in stabilizing it. Prompted by our recent finding that the zein-phosphatidylcholine hybrid nanoparticles (Z/PC-NP) provide an advanced drug carrier compared to PC-NP, we herein investigated the potential of Z/PC-NP as an improved ICG formulation. Dynamic light scattering analysis, transmission electron microscopy, and Fourier-transform infrared spectroscopy studies showed that ICG was encapsulated in Z/PC-NP without hampering the high colloidal stability of the Z/PC-NP. During storage, the Z/PC-NP almost completely inhibited the ICG aggregation, whereas the PC-NP did so partially. The Z/PC-NP also more effectively blocked the ICG degradation compared to the PC-NP. The phototoxicity of ICG encapsulated in Z/PC-NP on cancer cells was twofold higher than that in the PC-NP. The ICG encapsulated in Z/PC-NP, but not in PC-NP, maintained its photocytotoxicity after four-day storage. These findings highlight the promising potential of Z/PC-NP as an ICG formulation that provides a higher stabilization effect than PC-NP.

Nanocomposites-based targeted oral drug delivery systems with infliximab in a murine colitis model.

BACKGROUND: Infliximab (IFX), a TNF-α blocking chimeric monoclonal antibody, induces clinical response and mucosal healing in patients with inflammatory bowel disease (IBD). However, systemic administration of this agent causes unwanted side effects. Oral delivery of antibody therapeutics might be an effective treatment strategy for IBD compared to intravenous administration. RESULTS: All three carriers had a high encapsulation efficiency, narrow size distribution, and minimal systemic exposure. There was a higher interaction between nanocomposite carriers and monocytes compared to lymphocytes in the PBMC of IBD patients. Orally administered nanocomposite carriers targeted to inflamed colitis minimized systemic exposure. All IFX delivery formulations with nanocomposite carriers had a significantly less colitis-induced body weight loss, colon shortening and histomorphological score, compared to the DSS-treated group. AC-IFX-L and EAC-IFX-L groups showed significantly higher improvement of the disease activity index, compared to the DSS-treated group. In addition, AC-IFX-L and EAC-IFX-L alleviated pro-inflammatory cytokine expressions (Tnfa, Il1b, and Il17). CONCLUSION: We present orally administered antibody delivery systems which improved efficacy in murine colitis while reducing systemic exposure. These oral delivery systems suggest a promising therapeutic approach for treating IBD.

Ternary nanocomposite carriers based on organic clay-lipid vesicles as an effective colon-targeted drug delivery system: preparation and in vitro/in vivo characterization.

This study aimed to develop a new colon-targeted drug delivery system via the preparation of ternary nanocomposite carriers based on organic polymer, aminoclay and lipid vesicles. Budesonide (Bud), an anti-inflammatory drug was chosen as a model drug and encapsulated into three different formulations: liposome (Bud-Lip), aminoclay-coated liposome (AC-Bud-Lip), and Eudragit® S100-aminoclay double coated liposome (EAC-Bud-Lip). The formation of the aminoclay-lipid vesicle nanocomposite was confirmed by energy dispersive X-ray spectrum, transmission electron microscopy, and Fourier-transform infrared spectroscopy. All formulations were produced with a high encapsulation efficiency in a narrow size distribution. Drug release from EAC-Bud-Lip was approximately 10% for 2-h incubation at pH 1.2, implying the minimal drug release in acidic gastric condition. At pH 7.4, EAC-Bud-Lip underwent significant size reduction and exhibited drug release profiles similar to that from AC-Bud-Lip, implying the pH-dependent removal of the outer coating layer. Compared to free Bud solution, EAC-Bud-Lip achieved a higher drug uptake in Caco-2 cells and exhibited a stronger inhibition of TNF-α and IL-6 secretion in LPS-stimulated Raw264.7 cells. Furthermore, a bio-distribution study in mice demonstrated that Eudragit® S100-aminoclay dual coating led to a higher colonic distribution with a longer residence time, which correlated well with the delayed systemic drug exposure in rats. Taken together, the present study suggests that the ternary nanocomposite carrier consisting of Eudragit® S100, aminoclay, and lipid vesicle might be useful as an effective colon-targeted drug delivery system.

Krill Oil-Incorporated Liposomes As An Effective Nanovehicle To Ameliorate The Inflammatory Responses Of DSS-Induced Colitis.

BACKGROUND: Phosphatidylcholine (PC) and Omega-3 fatty acid (Omega-3) are promising therapeutic molecules for treating inflammatory bowel disease (IBD). PURPOSE: Based on the IBD therapeutic potential of nanoparticles, we herein sought to develop Omega-3-incorporated PC nanoparticles (liposomes) as an orally administrable vehicle for treating IBD. METHODS: Liposomes prepared with or without Omega-3 incorporation were compared in terms of colloidal stability and anitiinflammatory effects. RESULTS: The incorporation of free Omega-3 (alpha-linolenic acid, eicosapentaenoic acid or docosahexaenoic acid) into liposomes induced time-dependent membrane fusion, resulting in particle size increase from nm to µm during storage. In contrast, krill oil incorporation into liposomes (KO liposomes) did not induce the fusion and the particle size maintained <250 nm during storage. KO liposomes also maintained colloidal stability in simulated gastrointestinal conditions and exhibited a high capacity to entrap the IBD drug, budesonide (BDS). KO liposomes greatly suppressed the lipopolysaccharide-induced production of pro-inflammatory cytokines in cultured macrophages and completely restored inflammation-impaired membrane barrier function in an intestinal barrier model. In mice subjected to dextran sulfate sodium-induced colitis, oral administration of BDS-entrapped KO liposomes suppressed tumor necrosis factor-α production (by 84.1%), interleukin-6 production (by 35.3%), and the systemic level of endotoxin (by 96.8%), and slightly reduced the macroscopic signs of the disease. CONCLUSION: Taken together, KO liposomes may have great potential as a nanovehicle for oral delivery of IBD drugs.

Liposomal Formulations for Nose-to-Brain Delivery: Recent Advances and Future Perspectives.

Restricted drug entry to the brain that is closely associated with the existence of the blood brain barrier (BBB) has limited the accessibility of most potential active therapeutic compounds to the brain from the systemic circulation. Recently, evidences for the presence of direct nose-to-brain drug transport pathways have been accumulated by several studies and an intranasal drug administration route has gained attention as a promising way for providing direct access to the brain without the needs to cross to the BBB. Studies aiming for developing nanoparticles as an intranasal drug carrier have shown considerable promise in overcoming the challenges of intranasal drug delivery route. This review gives a comprehensive overview of works having investigated liposomes as a potential vehicle to deliver drugs to the brain through nose-to-brain route while considering the excellent biocompatibility and high potential of liposomes for clinical development. Herein, studies are reviewed with special emphasis on the impact of formulation factors, such as liposome composition and surface modification of liposomes with targeting moieties, in addition to intranasal environmental factors that may affect the extent/site of absorption of intranasally administered, liposome-encapsulated drugs.

Chitosan-coated liposomes to stabilize and enhance transdermal delivery of indocyanine green for photodynamic therapy of melanoma.

Indocyanine green (ICG) has been used clinically and noticed as a promising candidate for the topical melanoma photodynamic therapy (PDT). Despite its high potentials in topical PDT, the use of ICG has been hampered by the instability in aqueous solution. In the present study, chitosan-coated liposomes were adopted as a formulation strategy which could stabilize and enhance skin permeation of ICG. Chitosan-coating was verified by the significantly increased liposomal size and reversed zeta potential from negative to positive value by positive chitosan coating. Chitosan-coating liposomes protected ICG from degradation while uncoated liposomes did not. Moreover, they significantly increased cellular uptake and photocytotoxicity of ICG in B16-F10 melanoma cells in a chitosan-dependent manner. The skin permeation of ICG was also drastically improved by chitosan-coated liposomes. These findings emphasize the promising potential of ICG-loaded chitosan-coated liposomes for topical PDT of melanoma.

Comparison of 1-Palmitoyl-2-Linoleoyl-3-Acetyl-Rac-Glycerol-Loaded Self-Emulsifying Granule and Solid Self-Nanoemulsifying Drug Delivery System: Powder Property, Dissolution and Oral Bioavailability.

The main objective of this study was to compare the powder property, dissolution and bioavailability of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG)-loaded self-emulsifying granule system (SEGS) and solid self-nanoemulsifying drug delivery system (SNEDDS). Various SEGS formulations were prepared, and the effect of surfactant and binder on the drug solubility in them, leading to selecting sodium lauryl sulphate (SLS) and hydroxyl propyl methyl cellulose (HPMC). The SEGS and SNEDDS were prepared with PLAG/SLS/HPMC/calcium silicate/microcrystalline cellulose at the weight ratio of 1:0.25:0.1:0.5:3 employing the fluid bed granulation and spray-drying technique, respectively. Their powder properties were compared in terms of flow ability, emulsion droplet size, scanning electron microscopy, and powder X-ray diffraction. Furthermore, the solubility, dissolution, and oral bioavailability in rats of the SEGS were assessed in comparison with the SNEDDS. The SEGS and SNEDDS enhanced the solubility of the drug approximately 36- and 32-fold as compared with the drug alone; but they had no differences. The crystalline drug may exist in both the calcium silicate and microcrystalline cellulose (MCC) in the SEGS, but only in the calcium silicate in the SNEDDS. The SEGS had considerably improved the flow ability (Hausner ratio, 1.23 vs. 1.07; Carr index, 19.8 vs. 43.5%) and drug dissolution as compared with the SNEDDS. The SEGS and SNEDDS with double peak profiles, unlike the single peak of drug alone, showed a significantly higher plasma concentration and area under the curve (AUC), as compared with drug alone. Although they were not significantly different, the SEGS gave higher AUC than did the SNEDDS, suggesting its enhanced oral bioavailability of PLAG. Thus, the SEGS could be used as a powerful oral dosage form to improve the flow ability and oral bioavailability of PLAG, an oily drug.

Efficient induction of cell-mediated immunity to varicella-zoster virus glycoprotein E co-lyophilized with a cationic liposome-based adjuvant in mice.

Varicella zoster virus (VZV) is a neurotropic and lymphotropic alpha herpesvirus that causes varicella and herpes zoster (HZ). At a primary infection, VZV causes varicella in young children. Reactivation of latent VZV in sensory ganglia causes painful HZ in elderly people, occasionally leading to a serious complication, postherpetic neuralgia (PHN). A live attenuated VZV vaccine, the first vaccine licensed for the prevention of HZ and PHN is not very effective, while a recombinant subunit vaccine provides higher and longer protection against HZ. In the present study, we developed a new adjuvant system CIA09A, which is composed of cationic liposomes, the Toll-like receptor 4 (TLR4) agonist de-O-acylated lipooligosaccharide, and Quillaja saponin fraction QS-21. We then determined its adjuvant activity for recombinant VZV glycoprotein E (gE) in mice. Co-lyophilization of the liposomal adjuvant formulation with gE did not abolish the immune-stimulating activity. In fact, the CIA09A-adjuvanted gE vaccine was highly effective in eliciting both humoral and cellular immune responses to the recombinant gE protein and VZV in a VZV-primed mouse model. Furthermore, the frequency of gE-specific polyfunctional CD4+ T cells expressing interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-2 was significantly increased in mice immunized with the adjuvanted vaccine. These data indicate that co-lyophilization of protein antigens with CIA09A enables development of a liposome-adjuvanted vaccine in a single vial to induce strong cell-mediated immunity required for vaccine efficacy. Thus, the CIA09A-adjuvanted gE vaccine warrants further development as a new prophylactic vaccine against HZ.

Role of zein incorporation on hydrophobic drug-loading capacity and colloidal stability of phospholipid nanoparticles.

Liposome, phosphatidylcholine nanoparticle (PC-NP), is an attractive colloidal carrier of hydrophobic drugs but its clinical development is often limited by low drug-loading capacity and the physical instability. Zein is a water-insoluble amphiphilic protein obtained from the corn. We herein investigated a possibility to develop zein-phosphatidylcholine hybrid nanoparticle (Z/PC-NP) as an advanced hydrophobic drug carrier. By employing the conventional liposome preparation method with the addition of zein, Z/PC-NP were produced. The extent of zein incorporation in PC-NP was affected by PC composition. DSC demonstrated the lowered phase transition temperature of PC by zein and FTIR showed the appearance of weakened but clear amide bonds of zein as well as increased levels of heterogeneous hydrogen bonding of Z/PC-NP compared to PC-NP. DLS, TEM and cryo-TEM studies suggested Z/PC-NP to be spherical nanoparticles composed of a zein core and a zein-PC hybrid shell. Z/PC-NP exhibited a higher loading capacity for hydrophobic model drugs (paclitaxel, docetaxel, celecoxib and curcumin), than did the zein nanoparticle and PC-NP, while exhibiting an intermediate drug release rate. The serum stability and the storage stability of Z/PC-NP were greater than those of PC-NP. Zein functioned as a cryoprotectant of PC-NP during freeze-drying. Z/PC-NP may provide a promising nanoparticle carrier of hydrophobic drugs.

Hymenobacter segetis sp. nov., isolated from soil.

A polyphasic taxonomic study was performed on a novel strain designated as S7-3-11T, which was isolated from soil of the Gyeongsangnam-do province in Republic of Korea. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain S7-3-11T belongs to the genus Hymenobacter and is most closely related to Hymenobacter ruber PB156T (97.9%), Hymenobacter daeguensis 16F3Y-2T (97.8%), Hymenobacter glaciei VUG-A130T (97.7%), Hymenobacter soli PB17T (97.5%), Hymenobacter terrae DG7AT (97.5%), and Hymenobacter antarcticus VUG-A42aaT (97.3%). However, DNA-DNA hybridization results showed less than 50% relatedness with respect to the type strains of the six most closely related species. The DNA G + C content of strain S7-3-11T was 60.2 mol%. MK-7 was identified as the predominant respiratory quinone, and summed feature 3 (C16:1 ω7c/C16:1 ω6c; 21.5%), C15:0 iso (16.8%), C15:0 anteiso (16.2%), and C15:1 iso G (10.8%) were the major fatty acids. Phosphatidylethanolamine, an unidentified aminolipid, and an unidentified aminophospholipid were detected as major polar lipids. On the basis of the polyphasic evidence presented, strain S7-3-11T is considered to represent a novel species of the genus Hymenobacter, for which the name Hymenobacter segetis sp. nov. is proposed. The type strain is S7-3-11T (= KCTC 52732T = JCM 32197T).

Hymenobacter pedocola sp. nov., a novel bacterium isolated from soil.

Strain S12-2-1T was isolated from a soil sample collected in the Gyeongsangnam-do province of the Republic of Korea. The isolate is a Gram-stain-negative, aerobic, short, rod-shaped bacterium, and its colonies are red to pink in colour. Analysis of the 16S rRNA gene identified strain S12-2-1T as a member of the genus Hymenobacter in the family Cytophagaceae, with high levels of 16S rRNA gene sequence similarity to Hymenobacter arizonensis OR362-8T (97.7 %), Hymenobacter sedentarius DG5BT (97.4 %) and Hymenobacter humi DG31AT (97.2 %). The isolate was positive for catalase and oxidase, but negative for acid production from glucose. The growth of strain S12-2-1T was supported at 4-30 °C, pH 7-10 and in the presence of 0-0.5 % NaCl. Strain S12-2-1T contained menaquinone-7 as the predominant respiratory quinone, sym-homospermidine as the major polyamine and iso-C15 : 0, anteiso-C15 : 0 and summed feature 3 (C16 : 1ω7c/C16 : 1ω6c) as the major fatty acids. Phosphatidylethanolamine was the major polar lipid. The genomic DNA G+C content was 58.7 mol%. Phenotypic and chemotaxonomic data supported the assignment of the isolate to the genus Hymenobacter. However, strain S12-2-1T exhibited a relatively low level of DNA-DNA relatedness with H. humi (31.7 %), H. arizonensis (24.4 %) and H. sedentarius (21.3 %). Based on its phenotypic and genotypic properties, along with its phylogenetic distinctiveness, strain S12-2-1T should be considered a novel species in the genus Hymenobacter, for which the name Hymenobacter pedocola sp. nov. is proposed. The type strain is S12-2-1T (=KCTC 52730T=JCM 32198T).

Comparison of a revaprazan-loaded solid dispersion, solid SNEDDS and inclusion compound: Physicochemical characterisation and pharmacokinetics.

The aim of this research was to compare three strategies for enhancing the solubility of poorly water-soluble revaprazan hydrochloride: solid dispersion, solid SNEDDS and inclusion compound. The influence of polymers, surfactants and oils on the drug solubility was assessed, and via the chosen carriers, the three types of formulations were prepared utilising spray drying technique. Their physicochemical properties, solubility, dissolution and pharmacokinetics in rats were performed compared with revaprazan powder. Among the liquid SNEDDS formulations assessed, the compositions of revaprazan, peceol, Tween 80 and Labrasol (10:15:55:30, weight ratio) provided the smallest emulsion size. Moreover, this liquid SNEDDS and dextran were suspended/dissolved in distilled water, and spray-dried, producing an optimal revaprazan-loaded solid SNEDDS. The appropriate solid dispersion and inclusion compound were composed of revaprazan, hydroxypropylmethylcellulose and cremophor A25 (5:1.4:5.6) and drug and hydroxyl-ß-cyclodextrin (2.5:8.77), respectively. The crystalline drug was converted to an amorphous state in all formulations. In the solid dispersion, the drug was attached to the hydrophilic carrier. The solid SNEDDS and inclusion compound contained aggregate microspheres and separate microspheres, respectively. All formulations significantly increased the drug solubility, dissolution, plasma concentration and AUC compared with revaprazan powder. These properties were ranked in the order solid dispersion ≥ solid SNEDDS > inclusion compound. Particularly, the solid dispersion improved about 9500-fold drug solubility and 10-fold oral bioavailability. Thus, the improved properties were considerably dependent upon these techniques, although all of the techniques employed similar mechanisms. Among the strategies checked, the solid dispersion system would be recommended as an oral revaprazan-loaded pharmaceutical product.

Electrostatic interaction of tumor-targeting adenoviruses with aminoclay acquires enhanced infectivity to tumor cells inside the bladder and has better cytotoxic activity.

In a previous report, 3-aminopropyl functionalized magnesium phyllosilicate (aminoclay) improved adenovirus transduction efficiency by shielding the negative surface charges of adenovirus particles. The present study analyzed the physicochemical characterization of the electrostatic complex of adenoviruses with aminoclay and explored whether it could be utilized for enhancing tumor suppressive activity in the bladder. As a result of aminoclay-adenovirus nanobiohybridization, its transduction was enhanced in a dose-dependent manner, increasing transgene expression in bladder cancer cells and in in vivo animal models. Physicochemical studies demonstrated that positively charged aminoclay led to the neutralization of negative surface charges of adenoviruses, protection of adenoviruses from neutralizing antibodies and lowered transepithelial electrical resistance (TEER). As expected from the physicochemical properties, the aminoclay enabled tumor-targeting adenoviruses to be more potent in killing bladder cancer cells and suppressing tumor growth in orthotopic bladder tumors, suggesting that aminoclay would be an efficient, versatile and biocompatible delivery carrier for intravesical instillation of adenoviruses.