Elucidating the structural changes of cellulose molecules and dynamics of Na ions during the crystal transition from cellulose I to II in low temperature and low concentration NaOH solution.

Low-concentration alkali treatments at low temperatures facilitate the crystal transition of cellulose I to II. However, the transition mechanism remains unclear. Hence, in this study, we traced the transition using in situ solid-state 13C CP/MAS NMR, WAXS, and 23Na NMR relaxation measurements. In situ solid-state 13C CP/MAS NMR and WAXS measurements revealed that soaking cellulose in NaOH at low temperatures disrupts the intramolecular hydrogen bonds and lowers the crystallinity of cellulose. The dynamics of Na ions (NaOH) play a crucial role in causing these phenomena. 23Na NMR relaxation measurements indicated that the Na-ion correlation time becomes longer during the crystal transition. This transition requires the penetration of Na ions (NaOH) into the cellulose crystal and a reduction in Na-ion mobility, which occurs at low temperatures or high NaOH concentrations. The interactions between cellulose and NaOH disrupt intramolecular hydrogen bonds, inducing a conformational change in the cellulose molecules into a more stable arrangement. This weakens the hydrophobic interactions of cellulose, and facilitates the penetration of NaOH and water into the crystal, leading to the formation of alkali cellulose. Our findings suggest that a strategy to control NaOH dynamics could lead to the discovery of a novel preparation method for cellulose II.

Chemically Recyclable Unnatural (1→6)-Polysaccharides from Cellulose-Derived Levoglucosenone and Dihydrolevoglucosenone.

Unnatural polysaccharide analogs and their biological activities and material properties have attracted considerable research interest. However, these efforts often encounter challenges, especially those related to synthetic complexity and scalability. Here, we report the chemical synthesis of unnatural (1→6)-polysaccharides using levoglucosenone (LGO) and dihydrolevoglucosenone (Cyrene), which are derived from cellulose. Using a versatile monomer synthesis from LGO and Cyrene and cationic ring-opening polymerization, (1→6)-polysaccharides with various tailored substituent patterns are obtained. Additionally, environmentally benign and easy-to-handle organic Brønsted acid catalysts are investigated. This study demonstrates well-controlled first-order polymerization kinetics for the reactive (1S,5R)-6,8-dioxabicyclo[3,2,1]octane (DBO) monomer. The synthesized (1→6)-polysaccharides exhibit high thermal stability and form amorphous solids under ambient conditions, which could be processed into highly transparent self-standing films. Additionally, these polymers exhibit excellent closed-loop chemical recyclability. This study provides an important approach to explore the chemical spaces of unnatural polysaccharides and contributes to the development of sustainable polymer materials from abundant biomass resources.

Rotaxane Formation of Multicyclic Polydimethylsiloxane in a Silicone Network: A Step toward Constructing "Macro-Rotaxanes" from High-Molecular-Weight Axle and Wheel Components.

Rotaxanes consisting of a high-molecular-weight axle and wheel components (macro-rotaxanes) have high structural freedom, and are attractive for soft-material applications. However, their synthesis remains underexplored. Here, we investigated macro-rotaxane formation by the topological trapping of multicyclic polydimethylsiloxanes (mc-PDMSs) in silicone networks. mc-PDMS with different numbers of cyclic units and ring sizes was synthesized by cyclopolymerization of a α,ω-norbornenyl-functionalized PDMS. Silicone networks were prepared in the presence of 10-60 wt % mc-PDMS, and the trapping efficiency of mc-PDMS was determined. In contrast to monocyclic PDMS, mc-PDMSs with more cyclic units and larger ring sizes can be quantitatively trapped in the network as macro-rotaxanes. The damping performance of a 60 wt % mc-PDMS-blended silicone network was evaluated, revealing a higher tan δ value than the bare PDMS network. Thus, macro-rotaxanes are promising as non-leaching additives for network polymers.

Effect of degree of substitution on the microphase separation and mechanical properties of cellooligosaccharide acetate-based elastomers.

Thermoplastic elastomers (TPEs) have long been used in a wide range of industries. However, most existing TPEs are petroleum-derived polymers. To realize environmentally benign alternatives to conventional TPEs, cellulose acetate is a promising TPE hard segment because of its sufficient mechanical properties, availability from renewable sources, and biodegradability in natural environments. Because the degree of substitution (DS) of cellulose acetate governs a range of physical properties, it is a useful parameter for designing novel cellulose acetate-based TPEs. In this study, we synthesized cellulose acetate-based ABA-type triblock copolymers (AcCelx-b-PDL-b-AcCelx) containing a celloologosaccharide acetate hard A segment (AcCelx, where x is the DS; x = 3.0, 2.6, and 2.3) and a poly(δ-decanolactone) (PDL) soft B segment. Small-angle X-ray scattering showed that decreasing the DS of AcCelx-b-PDL-b-AcCelx resulted in the formation of a more ordered microphase-separated structure. Owing to the microphase separation of the hard cellulosic and soft PDL segments, all the AcCelx-b-PDL-b-AcCelx samples exhibited elastomer-like properties. Moreover, the decrease in DS improved toughness and suppressed stress relaxation. Furthermore, preliminary biodegradation tests in an aqueous environment revealed that the decrease in DS endowed AcCelx-b-PDL-b-AcCelx with greater biodegradability potential. This work demonstrates the usefulness of cellulose acetate-based TPEs as next-generation sustainable materials.

Molecular Weight-Dependent Oxidation and Optoelectronic Properties of Defect-Free Macrocyclic Poly(3-hexylthiophene).

The redox behaviors of macrocyclic molecules with an entirely π-conjugated system are of interest due to their unique optical, electronic, and magnetic properties. In this study, defect-free cyclic P3HT with a degree of polymerization (DPn) from 14 to 43 was synthesized based on our previously established method, and its unique redox behaviors arising from the cyclic topology were investigated. Cyclic voltammetry (CV) showed that the HOMO level of cyclic P3HT decreases from -4.86 eV (14 mer) to -4.89 eV (43 mer), in contrast to the linear counterparts increasing from -4.94 eV (14 mer) to -4.91 eV (43 mer). During the CV measurement, linear P3HT suffered from electro-oxidation at the chain ends, while cyclic P3HT was stable. ESR and UV-Vis-NIR spectroscopy suggested that cyclic P3HT has stronger dicationic properties due to the interactions between the polarons. On the other hand, linear P3HT showed characteristics of polaron pairs with multiple isolated polarons. Moreover, the dicationic properties of cyclic P3HT were more pronounced for the smaller macrocycles.

Size Control and Enhanced Stability of Silver Nanoparticles by Cyclic Poly(ethylene glycol).

Silver nanoparticles (AgNPs) are used in a wide range of applications, and the size control and stability of the nanoparticles are crucial aspects in their applications. In the present study, cyclized poly(ethylene glycol) (c-PEG) with various molecular weights, along with linear PEG with hydroxy chain ends (HO-PEG-OH) and methoxy chain ends (MeO-PEG-OMe) were applied for the Tollens' synthesis of AgNPs. The particle size was significantly affected by the topology and end groups of PEG. For example, the size determined by TEM was 40 ± 7 nm for HO-PEG5k-OH, 21 ± 4 nm for c-PEG5k, and 48 ± 9 nm for MeO-PEG5k-OMe when the molar ratio of PEG to AgNO3 (ω) was 44. The stability of AgNPs was also drastically improved by cyclization; the relative UV-Vis absorption intensity (A/A0 × 100%) at λmax to determine the proportion of persisting AgNPs in an aqueous NaCl solution (37.5 mM) was 58% for HO-PEG5k-OH, 80% for c-PEG5k, and 40% for MeO-PEG5k-OMe, despite the fact that AgNPs with c-PEG5k were much smaller than those with HO-PEG5k-OH and MeO-PEG5k-OMe.

PEGylation of silver nanoparticles by physisorption of cyclic poly(ethylene glycol) for enhanced dispersion stability, antimicrobial activity, and cytotoxicity.

Silver nanoparticles (AgNPs) are practically valuable in biological applications. However, no steady PEGylation has been established, which is essential for internal use in humans or animals. In this study, cyclic PEG (c-PEG) without any chemical inhomogeneity is physisorbed onto AgNPs to successfully PEGylate and drastically enhance the dispersion stability against physiological conditions, white light, and high temperature. In contrast, linear HO-PEG-OH and MeO-PEG-OMe do not confer stability to AgNPs, and HS-PEG-OMe, which is often used for gold nanoparticles, sulfidates the surface to considerably degrade the properties. TEM shows an essentially intact nanostructure of c-PEG-physisorbed AgNPs even after heating at 95 °C, while complete disturbance is observed for other AgNPs. Molecular weight- and concentration-dependent stabilization by c-PEG is investigated, and DLS and ζ-potential measurements prove the formation of a c-PEG layer on the surface of AgNPs. Furthermore, c-PEG-physisorbed AgNPs exhibit persistent antimicrobial activity and cytotoxicity.

Tailored Solid-State Carbohydrate Nanostructures Based on Star-Shaped Discrete Block Co-Oligomers.

Carbohydrates are key building blocks for advanced functional materials owing to their biological functions and unique material properties. Here, we propose a star-shaped discrete block co-oligomer (BCO) platform to access carbohydrate nanostructures in bulk and thin-film states via the microphase separation of immiscible carbohydrate and hydrophobic blocks (maltooligosaccharides with 1-4 glucose units and solanesol, respectively). BCOs with various star-shaped architectures and saccharide volume fractions were synthesized using a modular approach. In the bulk, the BCOs self-assembled into common lamellar, cylindrical, and spherical carbohydrate microdomains as well as double gyroid, hexagonally perforated lamellar, and Fddd network morphologies with domain spacings of ∼7 nm. In thin films, long-range-ordered periodic carbohydrate microdomains were fabricated via spin coating. Such controlled spatial arrangements of functional carbohydrate moieties on the nanoscale have great application potential in biomedical and nanofabrication fields.

Topology and Sequence-Dependent Micellization and Phase Separation of Pluronic L35, L64, 10R5, and 17R4: Effects of Cyclization and the Chain Ends.

The topology effects of cyclization on thermal phase transition behaviors were investigated for a series of amphiphilic Pluronic copolymers of both hydrophilic-hydrophobic-hydrophilic and hydrophobic-hydrophilic-hydrophobic block sequences. The dye solubilization measurements revealed the lowered critical micelle temperatures (TCMT) along with the decreased micellization enthalpy (ΔHmic) and entropy (ΔSmic) for the cyclized species. Furthermore, the transmittance and dynamic light scattering (DLS) measurements indicated a block sequence-dependent effect on the clouding phenomena, where a profound decrease in cloud point (Tc) was only found for the copolymers with a hydrophilic-hydrophobic-hydrophilic block sequence. Thus, the effect of cyclization on these critical temperatures was manifested differently depending on its block sequence. Finally, a comparison of the linear hydroxy-terminated, methoxy-terminated, and cyclized species indicated the effect of cyclization to be unique from a simple elimination of the terminal hydrophilic moieties.

Fabrication of Ultrafine, Highly Ordered Nanostructures Using Carbohydrate-Inorganic Hybrid Block Copolymers.

Block copolymers (BCPs) have garnered considerable interest due to their ability to form microphase-separated structures suitable for nanofabrication. For these applications, it is critical to achieve both sufficient etch selectivity and a small domain size. To meet both requirements concurrently, we propose the use of oligosaccharide and oligodimethylsiloxane as hydrophilic and etch-resistant hydrophobic inorganic blocks, respectively, to build up a novel BCP system, i.e., carbohydrate-inorganic hybrid BCP. The carbohydrate-inorganic hybrid BCPs were synthesized via a click reaction between oligodimethylsiloxane with an azido group at each chain end and propargyl-functionalized maltooligosaccharide (consisting of one, two, and three glucose units). In the bulk state, small-angle X-ray scattering revealed that these BCPs microphase separated into gyroid, asymmetric lamellar, and symmetric lamellar structures with domain-spacing ranging from 5.0 to 5.9 nm depending on the volume fraction. Additionally, we investigated microphase-separated structures in the thin film state and discovered that the BCP with the most asymmetric composition formed an ultrafine and highly oriented gyroid structure as well as in the bulk state. After reactive ion etching, the gyroid thin film was transformed into a nanoporous-structured gyroid SiO2 material, demonstrating the material's promising potential as nanotemplates.

Reinforcing Poly(methyl methacrylate) with Bacterial Cellulose Nanofibers Chemically Modified with Methacryolyl Groups.

Nanofibrillated bacterial cellulose (NFBC), a type of cellulose nanofiber biosynthesized by Gluconacetobacter sp., has extremely long (i.e., high-aspect-ratio) fibers that are expected to be useful as nanofillers for fiber-reinforced composite resins. In this study, we investigated a composite of NFBC and poly(methyl methacrylate) (PMMA), a highly transparent resin, with the aim of improving the mechanical properties of the latter. The abundant hydroxyl groups on the NFBC surface were silylated using 3-(methacryloyloxy)propyltrimethoxysilane (MPTMS), a silane coupling agent bearing a methacryloyl group as the organic functional group. The surface-modified NFBC was homogeneously dispersed in chloroform, mixed with neat PMMA, and converted into PMMA composites using a simple solvent-casting method. The tensile strength and Young's modulus of the composite increased by factors of 1.6 and 1.8, respectively, when only 0.10 wt% of the surface-modified NFBC was added, without sacrificing the maximum elongation rate. In addition, the composite maintained the high transparency of PMMA, highlighting that the addition of MPTMS-modified NFBC easily reinforce PMMA. Furthermore, interactions involving the organic functional groups of MPTMS were found to be very important for reinforcing PMMA.

Structural snapshot of a glycoside hydrolase family 8 endo-ß-1,4-glucanase capturing the state after cleavage of the scissile bond.

Bacterial cellulose (BC), which is produced by bacteria, is a biodegradable and biocompatible natural resource. Because of its remarkable physicochemical properties, BC has attracted attention for the development and manufacture of biomedical and industrial materials. In the BC production system, the enzyme endo-ß-1,4-glucanase, which belongs to glycoside hydrolase family 8 (GH8), acts as a cleaner by trimming disordered cellulose fibers to produce high-quality BC. Understanding the molecular mechanism of the endo-ß-1,4-glucanase would help in developing a reasonable biosynthesis of BC. Nevertheless, all of the steps in the reaction of this endo-ß-1,4-glucanase are not clear. This study confirms the BC hydrolytic activity of the endo-ß-1,4-glucanase from the BC-producing bacterium Enterobacter sp. CJF-002 (EbBcsZ) and reports crystal structures of EbBcsZ. Unlike in previously reported GH8 endo-ß-1,4-glucanase structures, here the base catalyst was mutated (D242A) and the structure of this mutant bound to cellooligosaccharide [EbBcsZ(D242A)CPT] was analyzed. The EbBcsZ(D242A)CPT structure showed two cellooligosaccharides individually bound to the plus and minus subsites of EbBcsZ. The glucosyl unit in subsite -1 presented a distorted 5S1 conformation, a novel snapshot of a state immediately after scissile-bond cleavage. In combination with previous studies, the reaction process of endo-ß-1,4-glucanase is described and the ß-1,4-glucan-trimming mechanism of EbBcsZ is proposed. The EbBcsZ(D242A)CPT structure also showed an additional ß-1,4-glucan binding site on the EbBcsZ surface, which may help to accept the substrate.

Topology-Dependent Interaction of Cyclic Poly(ethylene glycol) Complexed with Gold Nanoparticles against Bovine Serum Albumin for a Colorimetric Change.

Unique physical and chemical properties arising from a polymer topology recently draw significant attention. In this study, cyclic poly(ethylene glycol) (c-PEG) was found to significantly interact with bovine serum albumin (BSA), suggested by nuclear magnetic resonance, dynamic light scattering, and fluorescence spectroscopy. On the other hand, linear HO-PEG-OH and MeO-PEG-OMe showed no affinity. Furthermore, a complex of gold nanoparticles and c-PEG (AuNPs/c-PEG) attracted BSA to form aggregates, and the red color of the AuNPs dispersion evidently disappeared, whereas ones with linear PEG or without PEG did not demonstrate such a phenomenon. The interactions among BSA, AuNPs, and PEG were investigated by changing the incubation time and concentration of the components by using UV-Vis and fluorescence spectroscopy.

Facile Post-Carboxymethylation of Cellulose Nanofiber Surfaces for Enhanced Water Dispersibility.

To improve the water dispersibility of cellulose nanofibers without deteriorating the physical properties, it is necessary to develop methods that can selectively modify fiber surfaces. Herein, the reaction conditions for carboxymethylation of the surface of nanofibrillated bacterial cellulose were optimized using chloroacetic acid as an etherification agent. Carboxymethylation in a high-concentration alkaline solution (>5 wt %) in the presence of isopropanol caused the mercerization and carboxymethylation of not only the nanofiber surface but also the cellulose crystals within the nanofiber, resulting in nanofiber swelling and an increase in fiber width. In contrast, with a dilute alkaline aqueous solution (3 wt %), the nanofiber surface was successfully carboxymethylated without changing the inner structure. Furthermore, the morphology was not affected by the carboxymethylation reaction, and no fiber swelling occurred under these reaction conditions. When the substitution reaction proceeded only on the nanofiber surface, the maximum degree of substitution (i.e., the average number of carboxymethyl groups substituted per anhydroglucose residue in cellulose) was 0.091. After surface modification, the nanofibers became more negatively charged, which improved the dispersibility in water through electrostatic repulsion, resulting in a drastic increase in the transparency of the nanofiber dispersion. This method provides a general approach for the surface modification of cellulose nanofibers to increase water dispersibility.

Suzuki-Miyaura Catalyst-Transfer Polycondensation of Triolborate-Type Carbazole Monomers.

Herein, we report the Suzuki-Miyaura catalyst-transfer polycondensation (SCTP) of triolborate-type carbazole monomers, i.e., potassium 3-(6-bromo-9-(2-octyldodecyl)-9H-carbazole-2-yl)triolborate (M1) and potassium 2-(7-bromo-9-(2-octyldodecyl)-9H-carbazole-2-yl) triolborate (M2), as an efficient and versatile approach for precisely synthesizing poly[9-(2-octyldodecyl)-3,6-carbazole] (3,6-PCz) and poly[9-(2-octyldodecyl)-2,7-carbazole] (2,7-PCz), respectively. The SCTP of triolborate-type carbazole monomers was performed in a mixture of THF/H2O using an initiating system consisted of 4-iodobenzyl alcohol, Pd2(dba)3•CHCl3, and t-Bu3P. In the SCTP of M1, cyclic by-product formation was confirmed, as reported for the corresponding pinacolboronate-type monomer. By optimizing the reaction temperature and reaction time, we successfully synthesized linear end-functionalized 3,6-PCz for the first time. The SCTP of M2 proceeded with almost no side reaction, yielding 2,7-PCz with a functional initiator residue at the α-chain end. Kinetic and block copolymerization experiments demonstrated that the SCTP of M2 proceeded in a chain-growth and controlled/living polymerization manner. This is a novel study on the synthesis of 2,7-PCz via SCTP. By taking advantage of the well-controlled nature of this polymerization system, we demonstrated the synthesis of high-molecular-weight 2,7-PCzs (Mn = 5-38 kg mol-1) with a relatively narrow ÐM (1.35-1.48). Furthermore, we successfully synthesized fluorene/carbazole copolymers as well as 2,7-PCz-containing diblock copolymers, demonstrating the versatility of the present polymerization system as a novel synthetic strategy for well-defined polycarbazole-based materials.

Biofabrication of a Hyaluronan/Bacterial Cellulose Composite Nanofibril by Secretion from Engineered Gluconacetobacter.

Naturally occurring polysaccharides, such as cellulose, hemicellulose, and chitin, have roles in plant skeletons and/or related properties in living organisms. Their hierarchically regulated production systems show potential for designing nanocomposite fabrication using engineered microorganisms. This study has demonstrated that genetically engineered Gluconacetobacter hansenii (G. hansenii) individual cells can fabricate naturally composited nanofibrils by simultaneous production of hyaluronan (HA) and bacterial cellulose (BC). The cells were manipulated to contain hyaluronan synthase and UDP-glucose dehydrogenase genes, which are essential for HA biosynthesis. Fluorescence microscopic observations indicated the production of composited nanofibrils and suggested that HA secretion was associated with the cellulose secretory pathway in G. hansenii. The gel-like nanocomposite materials produced by the engineered G. hansenii exhibited superior properties compared with conventional in situ nanocomposites. This genetic engineering approach facilitates the use of G. hansenii for designing integrated cellulose-based nanomaterials.

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.

One-Shot Intrablock Cross-Linking of Linear Diblock Copolymer to Realize Janus-Shaped Single-Chain Nanoparticles.

Developing an efficient and versatile process to transform a single linear polymer chain into a shape-defined nanoobject is a major challenge in the fields of chemistry and nanotechnology to replicate sophisticated biological functions of proteins and nucleic acids in a synthetic polymer system. In this study, we performed one-shot intrablock cross-linking of linear block copolymers (BCPs) to realize single-chain nanoparticles (SCNPs) with two chemically compartmentalized domains (Janus-shaped SCNPs). Detailed structural characterizations of the Janus-shaped SCNP composed of polystyrene-block-poly(glycolic acid) revealed its compactly folded conformation and compartmentalized block localization, similar to the self-folded tertiary structures of natural proteins. Versatility of the one-shot intrablock cross-linking was demonstrated using several different BCP precursors. In addition, the Janus-shaped SCNP produce miniscule microphase-separated structures.

Cyclization of PEG and Pluronic Surfactants and the Effects of the Topology on Their Interfacial Activity.

A series of cyclic surfactants were synthesized from a poly(ethylene glycol) (PEG) homopolymer and Pluronic surfactants L35, L64, P123, F68, 10R5, and 17R4, and their interfacial activity depending on the topology, chain ends, and block sequence was investigated. The cyclization was performed in a single step through etherification of the PEG homopolymer and the hydrophilic-hydrophobic-hydrophilic (ABA type) poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) (PEG-PPG-PEG), while the hydrophobic-hydrophilic-hydrophobic (BAB type) PPG-PEG-PPG was cyclized via acetalization. The cyclized surfactants were rigorously characterized by nuclear magnetic resonance spectroscopy and size exclusion chromatography. Cyclization of the surfactants induced a significant decrease in the hydrodynamic volume, which was more pronounced than that of the PEG homopolymer. Surface tension (γ) measurements indicated that the interfacial activity of the cyclized surfactants is stronger than their corresponding linear precursors, due to the increase in the surfactant density at the air-water interface as a consequence of the decreased molecular occupational area (A) upon cyclization. In the case of the PEG homopolymer, A considerably decreased from 410 Å2 for the linear PEG prepolymer to 100 Å2 for the cyclized PEG product. While the effects of chain-end groups were found to be limited to surfactants of relatively small molecular weights, the influence of cyclization depended strongly on the hydrophilic/hydrophobic ratio; the higher the PEG composition the surfactants had, the larger the decrease in γ and A; in other words, stronger enhancement in the interfacial activity was observed.

Therapeutic efficacy of a paclitaxel-loaded nanofibrillated bacterial cellulose (PTX/NFBC) formulation in a peritoneally disseminated gastric cancer xenograft model.

Nano-fibrillated bacterial cellulose (NFBC) is a safe, biocompatible material that can be prepared by culturing a cellulose-producing bacterium in a culture supplemented with carboxymethylcellulose (CMC) or hydroxypropylcellulose (HPC). CM-NFBC and HP-NFBC, prepared using CMC or HPC, show hydrophilicity and amphiphilicity, respectively, and thus they could be useful carriers for hydrophobic anticancer agents such as paclitaxel (PTX). In the present study, we prepared novel PTX formulations for intraperitoneal administration by associating PTX with either CM-NFBC or HP-NFBC and studied their therapeutic efficacy on peritoneally disseminated gastric cancer in a xenograft nude mouse model. Freeze-dried PTX formulations (PTX/CM-NFBC and PTX/HP-NFBC) were quickly reconstituted with saline without any foaming, compared to nanoparticle albumin-bound PTX (nab-PTX, Abraxane®). Both PTX/NFBC formulations extended the mean survival times in our xenograft murine models compared with either free PTX or nab-PTX. The PTX/NFBC formulations reduced systemic side effects of free PTX relating to weight loss. In our disseminated gastric peritoneal cancer model, the PTX/NFBC formulation increased the therapeutic index for PTX by increasing the therapeutic efficacy and decreasing toxicity. NFBCs should receive consideration as improved carriers for the clinical delivery of hydrophobic anticancer drugs such as PTX in malignancies in the abdominal cavity with peritoneal metastasis and dissemination.