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.

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.

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.

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.

Enhanced dispersion stability of gold nanoparticles by the physisorption of cyclic poly(ethylene glycol).

Nano-sized metal particles are attracting much interest in industrial and biomedical applications due to the recent progress and development of nanotechnology, and the surface-modifications by appropriate polymers are key techniques to stably express their characteristics. Herein, we applied cyclic poly(ethylene glycol) (c-PEG), having no chemical inhomogeneity, to provide a polymer topology-dependent stabilization for the surface-modification of gold nanoparticles (AuNPs) through physisorption. By simply mixing c-PEG, but not linear counterparts, enables AuNPs to maintain dispersibility through freezing, lyophilization, or heating. Surprisingly, c-PEG endowed AuNPs with even better dispersion stability than thiolated PEG (HS-PEG-OMe). The stronger affinity of c-PEG was confirmed by DLS, ζ-potential, and FT-IR. Furthermore, the c-PEG system exhibited prolonged blood circulation and enhanced tumor accumulation in mice. Our data suggests that c-PEG induces physisorption on AuNPs, supplying sufficient stability toward bio-medical applications, and would be an alternative approach to the gold-sulfur chemisorption.

Advanced functionalization of polyhydroxyalkanoate via the UV-initiated thiol-ene click reaction.

Polyhydroxyalkanoates (PHAs) incorporating vinyl-bearing 3-hydroxyalkanoates were prepared in 8.5-12.9 g L(-1) yield. The molar ratios (0-16 mol%) of the vinyl-bearing 3-hydroxyalkanoate derivatives were controlled by the continuous feeding of undecylenate at various concentrations. Subsequently, the PHAs were functionalized by UV-initiated thiol-ene click reaction and chemical modification. (1)H NMR spectra suggested that 3-mercaptopropionic acid and 2-aminoethanethiol were successfully introduced into the vinyl-bearing PHA. Subsequently, chemical modification using fluorescein or a fibronectin active fragment (GRGDS) was attempted. The former yielded a PHA derivative capable of emitting fluorescence under UV irradiation, which was useful for determining the miscibility of PHA in a composite film comprising poly-ʟ-lactic acid (PLLA) and PHA. In the latter case, PHA bearing GRGDS peptides exhibited cell adhesiveness, suggesting that its biocompatibility was improved upon peptide introduction. Taken together, the UV-initiated thiol-ene click reaction was demonstrated to be useful in PHA modification.

Isolation and characterization of Bacillus sp. INT005 accumulating polyhydroxyalkanoate (PHA) from gas field soil.

A gram-positive bacterium (designated strain INT005) that accumulated polyhydroxyalkanoate (PHA) was isolated from gas field soil. From its morphological and physiological properties and the partial nucleotide sequence (about 500 bp) of its 16S rDNA, it was suggested that strain INT005 was similar to several species of the genus Bacillus. We confirmed that strain INT005 is a Bacillus sp. The PHA productivities of strain INT005 were higher than those of Bacillus megaterium and Ralstonia eutropha at 37-45 degrees C reported to date, and it was suggested that the PHA synthase of INT005 may exhibit moderate thermostability. The bacterium had the ability to produce poly(3-hydroxybutyrate), poly(3-hydroxybutyrate-co-3-hydroxyvalerate), poly(3-hydroxybutyrate-co-3-hydroxyhexanoate), poly(3-hydroxybutyrate-co-4-hydroxybutyrate-co-3-hydroxyhexanoate), and poly(3-hydroxybutyrate-co-6-hydroxyhexanoate-co-3-hydroxyhexanoate) from the appropriate carbon sources. The PHA synthase from INT005 showed similar substrate specificity to those of class I and III PHA synthases and strain INT005 produced PHAs with various monomer compositions. From the analysis of monomer composition and PHA accumulation in the presence of acrylic acid, it was suggested that de novo fatty acid synthesis and beta-oxidation are involved in the PHA synthesis of Bacillus sp. INT005. Since Bacillus sp. INT005 could synthesize PHA even at 45 degrees C and PHAs with various monomer compositions, and only one report on the cloning of the synthesis-related genes from a Bacillus species (B. megaterium) has been published;Bacillus sp. INT005 is thought to be very valuable source of PHA synthesis-related genes.