Hochuekkito, a Kampo (traditional Japanese herbal) Medicine, Enhances Mucosal IgA Antibody Response in Mice Immunized with Antigen-entrapped Biodegradable Microparticles

The effect of oral administration of Hochuekkito (HET; Bu-Zhong-Yi-Qi-Tang in Chinese), a traditional Japanese herbal medicine, on mucosal IgA immune response was investigated. To induce the antigen-specific antibodies in mucosal site, ovalbumin (OVA)-entrapped biodegradable microparticles (OVA-microparticles) were used as an antigen. Mice were orally immunized with OVA-microparticles for 3 successive days with intragastric gavage. From 7 days after the onset of immunization, the mice were boosted twice a week with the same antigen for 2 weeks. HET or water alone was orally administered to the mice via the intragastric route from 7 days before to 27 days after the onset of immunization. Although no significant change in total secretory IgA antibody level was observed in intestinal and nasal washes, OVA-specific IgA titers in intestinal washes were significantly enhanced by oral administration of HET. When lymphocytes from spleen, peripheral blood and Payer's patches were investigated for cytokines production, it was found that the IFN-γ secretion from the lymphocytes was increased by the administration of HET. Microarray analysis of Peyer's patch cells revealed enhanced expression of L-selectin gene. The increase of L-selectin positive cells in B lymphocytes fraction was observed in Peyer's patch cells and peripheral blood mononuclear cells by flow cytometry. These results suggest that the enhanced IFN-γ secretion and increased population of L-selectin positive B lymphocytes by orally administered HET may partly contribute to enhancement of IgA immune response against intestinal antigens, and orally administered HET may strengthen defensive systems against various pathogens and food antigens in intestine

Comunidade de Colêmbolos em florestas decíduas e em plantações da conífera Cryptomeria japonica no Japão central

Collembolan communities in conifer plantations (Japanese cedar, Cryptomeria japonica) and secondary deciduous broad-leaved forests of varying ages were investigated to determine the extent to which forest conversion (broad-leaved to coniferous) affects the species richness and assemblage composition of Collembola in central Japan. Density and total species richness of Collembola not differed between the broad-leaved and cedar forests except immediately after clear-cutting. The amount of forest-floor organic matter was larger in cedar forests and positively correlated with the species richness of detritus feeders. Species richness of fungal feeders and sucking feeders positively correlated with the species richness of forest-floor plants. There was difference in collembolan species composition between the forest types. The age of the forests seemed to have only small importance for the collembolan community, except during the first four years after clear-cutting. The conversion to artificial cedar stands has not reduced the abundance or species richness of collembolan communities, but has affected community composition. Differences in species composition may be related to the ground floras.As comunidades de colÛmbolos nas plantaþ§es da conÝfera Cryptomeria japonica (cedro japonês) e florestas decíduas secundárias de várias idades foram investigadas para determinar até que ponto a conversão da floresta decídua em conífera afeta a riqueza das espécies e a composição das comunidades de colêmbolos no Japão central. A densidade e a riqueza total de espécies de Collembola não foram diferentes entre as florestas decíduas e de cedro, exceto imediatamente depois do corte raso. A quantidade de matéria orgânica acumulada no solo foi maior sob cedro e positivamente correlacionada com a riqueza de espécies de detritívoros. A riqueza de espécies de fungívoros e sugadores foi positivamente correlacionada à riqueza de espécies de plantas do estrato herbáceo da floresta. Houve diferença na composição das espécies de colêmbolos entre os tipos de floresta. A idade das florestas parece ter pouca importância para a comunidade de colêmbolos, exceto nos primeiros quatro anos após o corte raso. Concluiu-se que a conversão da floresta decídua em plantações de cedro japonês não causou diminuição na abundância e na riqueza das espécies das comunidades de colêmbolos, mas afetou a composição dessas comunidades. As diferenças na composição das espécies podem ser relacionadas ao desenvolvimento de plantas do estrato herbáceo da floresta

Usefulness of percutaneous estradiol-loaded PLGA-PEG-PLGA nanoparticles for the treatment of osteoporosis

Compared with poly (dl-lactide-co-glycolide) (PLGA) nanoparticles, triblock copolymer (PLGA-PEG-PLGA) nanoparticles composed of PLGA and polyethylene glycol (PEG) may improve the skin permeability of drugs. In this study, the usefulness of estradiol-loaded (E2-loaded) PLGA-PEG-PLGA nanoparticles in the treatment of osteoporosis was investigated by comparison with E2-loaded PLGA nanoparticles. The cumulative E2 permeation of each nanoparticle through rat skin was quantified using a Franz cell. The results showed that PLGA-PEG-PLGA nanoparticles had significantly higher permeation than PLGA nanoparticles. Next, in vivo treatment experiments were conducted using an ovariectomized rat model of osteoporosis. Nanoparticles were administered once per week in combination with iontophoresis. At 6 weeks after the initiation of treatment, significant improvement in bone density was observed in the treated group compared with the untreated group. The improvement in bone density tended to be greater in the PLGA-PEG-PLGA nanoparticle group versus the PLGA nanoparticle group. This may be attributed to the higher hydrophilicity of the particle surface of PLGA-PEG-PLGA nanoparticles compared with PLGA nanoparticles and the improved skin permeability of the particles through the trans-adnexal pathway

pH-Sensitive Amphiphilic Diblock Polyphosphoesters with Lactate Units: Synthesis and Application as Drug Carriers

pH-sensitive amphiphilic diblock polyphosphoesters containing lactic acid units were synthesized by multistep one-pot polycondensation reactions. They comprise acid-labile P(O)-O-C and C(O)-O-C bonds, the cleavage of which depends on the pH of the medium. The structure of these copolymers was characterized by 1H, 13C {H}, 31P NMR, and size exclusion chromatography (SEC). The newly synthesized polymers self-assembled into the micellar structure in an aqueous solution. The effects of the molecular weight of the copolymer and the length of the hydrophobic chain on micelle formation and stabilityand micelle size were studied via dynamic light scattering (DLS). Drug loading and encapsulation efficiency tests using doxorubicin revealed that hydrophobic drugs can be delivered by copolymers. It was established that the molecular weight of the copolymer, length of the hydrophobic chain and content of lactate units affects the size of the micelles, drug loading, and efficiency of encapsulation. A copolymer with 10.7% lactate content has drug loading (3.2 ± 0.3) and efficiency of encapsulation (57.4 ± 3.2), compared to the same copolymer with 41.8% lactate content (1.63%) and (45.8%), respectively. It was demonstrated that the poly[alkylpoly(ethylene glycol) phosphate-b-alkylpoly(ethylene glycol)lactate phosphate] DOX system has a pH-sensitive response capability in the result in which DOX was selectively accumulated into the tumor, where pH is acidic. The results obtained indicate that amphiphilic diblock polyphosphoesters have potential as drug carriers

Thermoresponsive Polyphosphoester via Polycondensation Reactions: Synthesis, Characterization, and Self-Assembly

Using a novel strategy, amphiphilic polyphosphoesters based on poly(oxyethylene H-phosphonate)s (POEHP) with different poly(ethylene glycol) segment lengths and aliphatic alcohols with various alkyl chain lengths were synthesized using polycondensation reactions. They were characterized by 1H NMR, 13C {H} NMR 31P NMR, IR, and size exclusion chromatography (SEC). The effects of the polymer structure on micelle formation and stability, micelle size, and critical micelle temperature were studied via dynamic light scattering (DLS). The hydrophilic/hydrophobic balance of these polymers can be controlled by changing the chain lengths of hydrophilic PEG and hydrophobic alcohols. A solubilizing test, using Sudan III, revealed that hydrophobic substances can be incorporated inside the hydrophobic core of polymer associates. Loading capacity depends on the length of alkyl side chains. The results obtained indicate that these structurally flexible polymers have the potential as drug carriers