Doxorubicin Embedded into Nanofibrillated Bacterial Cellulose (NFBC) Produces a Promising Therapeutic Outcome for Peritoneally Metastatic Gastric Cancer in Mice Models via Intraperitoneal Direct Injection

Natural materials such as bacterial cellulose are gaining interest for their use as drug-delivery vehicles. Herein, the utility of nanofibrillated bacterial cellulose (NFBC), which is produced by culturing a cellulose-producing bacterium (Gluconacetobacter intermedius NEDO-01) in a medium supplemented with carboxymethylcellulose (CMC) that is referred to as CM-NFBC, is described. Recently, we demonstrated that intraperitoneal administration of paclitaxel (PTX)-containing CM-NFBC efficiently suppressed tumor growth in a peritoneally disseminated cancer xenograft model. In this study, to confirm the applicability of NFBC in cancer therapy, a chemotherapeutic agent, doxorubicin (DXR), embedded into CM-NFBC, was examined for its efficiency to treat a peritoneally disseminated gastric cancer via intraperitoneal administration. DXR was efficiently embedded into CM-NFBC (DXR/CM-NFBC). In an in vitro release experiment, 79.5% of DXR was released linearly into the peritoneal wash fluid over a period of 24 h. In the peritoneally disseminated gastric cancer xenograft model, intraperitoneal administration of DXR/CM-NFBC induced superior tumor growth inhibition (TGI = 85.5%) by day 35 post-tumor inoculation, compared to free DXR (TGI = 62.4%). In addition, compared with free DXR, the severe side effects that cause body weight loss were lessened via treatment with DXR/CM-NFBC. These results support the feasibility of CM-NFBC as a drug-delivery vehicle for various anticancer agents. This approach may lead to improved therapeutic outcomes for the treatment of intraperitoneally disseminated cancers

Chemo-enzymatic synthesis of polyhydroxyalkanoate by an improved two-phase reaction system (TPRS)

In our previous paper, we synthesized poly-3-hydroxybutyrate [P(3HB)] by using the water-organic solvent two-phase reaction system (TPRS), in which thiophenyl (R)-3-hydroxybutyrate [(R)-3HBTP] was used as a precursor of 3HBCoA. We have developed an improved TPRS for the chemo-enzymatic synthesis of polyhydroxyalkanoate (PHA). In this method, acetyl thioester of ethyl thioglycolate (AcETG) was used as a precursor of acetylCoA (AcCoA), which was a donor of CoA. The AcCoA was formed by the ester exchange reaction between CoA in the water phase and AcETG in the organic solvent phase. The AcCoA and free 3-hydroxybutyrate (3HB) in the water phase were converted into 3HBCoA and acetate by a CoA-transfer reaction of propionylCoA transferase (PCT). The synthesized 3HBCoA was polymerized sequentially by PHA synthase, and P(3HB) was successfully formed. The maximal yield of P(3HB) was 1.2 g/l under the optimal reaction condition; this is comparable to that of in vivo PHA production. Furthermore, the number of enzymes was reduced and enzyme preparation was simplified by the construction of a fusion protein, PCT-PhaC. The chemo-enzymatic synthesis of P(3HB-co-3-hydroxypropionate) and P(3HB-co-3-mercaptopropionate) was also achieved by the improved TPRS using the fusion protein

Nanofibrillated Bacterial Cellulose Modified with (3-Aminopropyl)trimethoxysilane under Aqueous Conditions: Applications to Poly(methyl methacrylate) Fiber-Reinforced Nanocomposites

The development of eco-friendly fiber-reinforced composite resins is an important objective from an environmental perspective, and nanofibrillated bacterial cellulose (NFBC), with extremely long high-aspect-ratio fibers, is a filler material with high potential for use in such composite resins. In this study, we investigated chemical modification of the surfaces of NFBC fibers by coupling with (3-aminopropyl)trimethoxysilane and fabricated nanocomposite materials using the prepared surface-modified NFBC. The product prepared by the one-pot reaction of (3-aminopropyl)trimethoxysilane with NFBC microfibrils dispersed in aqueous acid retained the same nanofibril structure as the intact NFBC. The degree of molar substitution and the silicon states on the surface of the product depended on the NFBC/(3-aminopropyl)trimethoxysilane ratio. The thermal analysis revealed that the thermal degradation temperature of the products increases with an increase of degree of molar substitution. Highly transparent (78-89% at 600 nm) poly(methyl methacrylate)-based nanocomposites were prepared by solvent casting; the nanocomposite containing 1.0 wt % (3-aminopropyl)-trimethoxysilylated NFBC was only 8% less transparent than neat poly(methyl methacrylate) at 600 nm. In addition, the tensile strength of the nanocomposite was more than twice that of neat poly(methyl methacrylate) when 1 wt of the surface-modified NFBC was added. The surface-modified NFBC is expected to be a reinforcing nanofiber material that imparts excellent physical properties to fiber-reinforced resins

Isolation of a thermotolerant bacterium producing medium-chain-length polyhydroxyalkanoate

Aims: The aim of the present study was to isolate a thermotolerant microorganism that produces polyhydroxyalkanoates (PHAs) composed of medium-chain-length (mcl)-HA units from a biodiesel fuel (BDF) by-product as a carbon source. Methods and Results: We successfully isolated a thermotolerant microorganism, strain SG4502, capable to accumulate mcl-PHA from a BDF by-product as a carbon source at a cultivation temperature of 45℃. The strain could also produce mcl-PHA from acetate, octanoate, and dodecanoate as sole carbon sources at cultivation temperatures up to 55℃. Taxonomic studies and 16S rRNA gene sequence analysis revealed that strain SG4502 was phylogenetically affiliated with species of the genus Pseudomonas. This study is the first report of PHA synthesis by a thermotolerant Pseudomonas. Conclusions: A novel thermotolerant bacterium capable to accumulate mcl-PHA from a BDF by-product was successfully isolated. Significance and Impact of the Study: A major issue regarding industrial production of microbial PHAs is their much higher production cost compared with conventional petrochemical-based plastic materials. Especially significant are the cost of a fermentative substrate and the running cost to maintain a temperature suitable for microbial growth. Thus, strain SG4502, isolated in this study, which assimilates BDF by-product and produces PHA at high temperature, would be very useful for practical application in industry