Enhanced Oral Bioavailability of Rivaroxaban-Loaded Microspheres by Optimizing the Polymer and Surfactant Based on Molecular Interaction Mechanisms.

This study aimed to develop microspheres using water-soluble carriers and surfactants to improve the solubility, dissolution, and oral bioavailability of rivaroxaban (RXB). RXB-loaded microspheres with optimal carrier (poly(vinylpyrrolidone) K30, PVP) and surfactant (sodium lauryl sulfate (SLS)) ratios were prepared. 1H NMR and Fourier transform infrared (FTIR) analyses showed that drug-excipient and excipient-excipient interactions affected RXB solubility, dissolution, and oral absorption. Therefore, molecular interactions between RXB, PVP, and SLS played an important role in improving RXB solubility, dissolution, and oral bioavailability. Formulations IV and VIII, containing optimized RXB/PVP/SLS ratios (1:0.25:2 and 1:1:2, w/w/w), had significantly improved solubility by approximately 160- and 86-fold, respectively, compared to RXB powder, with the final dissolution rates improved by approximately 4.5- and 3.4-fold, respectively, compared to those of RXB powder at 120 min. Moreover, the oral bioavailability of RXB was improved by 2.4- and 1.7-fold, respectively, compared to that of RXB powder. Formulation IV showed the highest improvement in oral bioavailability compared to RXB powder (AUC, 2400.8 ± 237.1 vs 1002.0 ± 82.3 h·ng/mL). Finally, the microspheres developed in this study successfully improved the solubility, dissolution rate, and bioavailability of RXB, suggesting that formulation optimization with the optimal drug-to-excipient ratio can lead to successful formulation development.

Thickness-Tunable Eggshell Membrane Hydrolysate Nanocoating with Enhanced Cytocompatibility and Neurite Outgrowth.

The eggshell membrane is one of the easily obtainable natural biomaterials, but has been neglected in the biomaterial community, compared with marine biomaterials and discarded as a food waste. In this work, we utilized the ESM hydrolysate (ESMH), which was obtained by the enzymochemical method, as a bioactive functional material for interfacial bioengineering, exemplified by thickness-tunable, layer-by-layer (LbL) nanocoating with the Fe(III)-tannic acid (TA) complex. [Fe(III)-TA/ESMH] LbL films, ending with the ESMH layer, showed great cytocompatiblility with HeLa cells and even primary hippocampal neuron cells. More importantly, the films were found to be neurochemically active, inducing the acceleration of neurite outgrowth for the long-term neuron culture. We believe that the ability for building cytocompatible ESMH films in a thickness-tunable manner would be applicable to a broad range of different nanomaterials in shape and size and would be utilized with multimodal functionalities for biomedical applications, such as bioencapsulation, theranostics, and regenerative medicine.

Comparative Study on Surface-Initiated ATRP and SI-ARGET ATRP of Oligo(Ethylene Glycol) Methacrylate on Gold.

Oligo(ethylene glycol) methacrylate (OEGMA) was polymerized from a polymerization initiator-presenting gold substrate by Activator ReGenerated by Electron Transfer Atom Transfer Radical Polymerization (ARGET ATRP) in water. Compared with the normal surface-initiated ATRP (SI-ATRP), SI-ARGET ATRP of OEGMA proceeded smoothly in the presence of air with L-ascorbic acid as a reducing agent and a CuBr2/2,2'-bipyridyl complex at the ppm level. In addition, SI-ARGET ATRP did not require the additional steps for removing a polymerization inhibitor from the OEGMA monomer and for deoxygenating the solvent. The ellipsometric measurements showed that the polymerized OEGMA (pOEGMA) films prepared by SI-ARGET ATRP were on average 10 times thicker than those prepared by normal SI-ATRP with the same monomer concentration and polymerization time.

Development of a regenerative porous PLCL nerve guidance conduit with swellable hydrogel-based microgrooved surface pattern via 3D printing.

Peripheral nerve injury causes severe loss of motor and sensory functions, consequently increasing morbidity in affected patients. An autogenous nerve graft is considered the current gold standard for reconstructing nerve defects and recovering lost neurological functions; however, there are certain limitations to this method, such as limited donor nerve supply. With advances in regenerative medicine, recent research has focused on the fabrication of tissue-engineered nerve grafts as promising alternatives to the autogenous nerve grafts. In this study, we designed a nerve guidance conduit using an electrospun poly(lactide-co-ε-caprolactone) (PLCL) membrane with a visible light-crosslinked gelatin hydrogel. The PLCL nanoporous membrane with permeability served as a flexible and non-collapsible epineurium for the nerve conduit; the inner-aligned gelatin hydrogel paths were fabricated via 3D printing and a photocrosslinking system. The resultant gelatin hydrogel with microgrooved surface pattern was established as a conducting guidance path for the effective regeneration of axons and served as a reservoir that can incorporate and release bioactive molecules. From in vivo performance tests using a rat sciatic nerve defect model, our PLCL/gelatin conduit demonstrated successful axonal regeneration, remyelination capacities and facilitated functional recovery. Hence, the PLCL/gelatin conduit developed in this study is a promising substitute for autogenous nerve grafts. STATEMENT OF SIGNIFICANCE: Nerve guidance conduits (NGCs) are developed as promising recovery techniques for bridging peripheral nerve defects. However, there are still technological limitations including differences in the structures and components between natural peripheral nerve and NGCs. In this study, we designed a NGC composed of an electrospun poly(lactide-co-ε-caprolactone) (PLCL) membrane and 3D printed inner gelatin hydrogel to serve as a flexible and non-collapsible epineurium and a conducting guidance path, respectively, to mimic the fascicular structure of the peripheral nerve. In particular, in vitro cell tests clearly showed that gelatin hydrogel could guide the cells and function as a reservoir that incorporate and release nerve growth factor. From in vivo performance tests, our regenerative conduit successfully led to axonal regeneration with effective functional recovery.

A Decade of Advances in Single-Cell Nanocoating for Mammalian Cells.

Strategic advances in the single-cell nanocoating of mammalian cells have noticeably been made during the last decade, and many potential applications have been demonstrated. Various cell-coating strategies have been proposed via adaptation of reported methods in the surface sciences and/or materials identification that ensure the sustainability of labile mammalian cells during chemical manipulation. Here an overview of the methodological development and potential applications to the healthcare sector in the nanocoating of mammalian cells made during the last decade is provided. The materials used for the nanocoating are categorized into polymers, hydrogels, polyphenolic compounds, nanoparticles, and minerals, and the corresponding strategies are described under the given set of materials. It also suggests, as a future direction, the creation of the cytospace system that is hierarchically composed of the physically separated but mutually interacting cellular hybrids.

Effect of chitin/silk fibroin nanofibrous bicomponent structures on interaction with human epidermal keratinocytes.

To fabricate a biomimetic nanostructured bicomponent scaffolds, two types of chitin/silk fibroin (SF) nanofibrous scaffolds (blend scaffolds and hybrid scaffolds) were prepared by electrospinning or simultaneous electrospinning of chitin/SF solutions. The chitin/SF bicomponent scaffolds were after-treated with water vapor, and their nanofibrous structures were almost maintained. From the cytocompatibility and cell behavior on the chitin/SF blend or hybrid nanofibrous scaffolds, the hybrid matrix with 25% chitin and 75% SF as well as the chitin/SF blend nanofibers could be a potential candidate for tissue engineering scaffolds.

[Short-term therapy with pegylated interferon plus ribavirin for the chronic hepatitis C genotype 2 patients].

BACKGROUND/AIMS: The standard treatment for chronic hepatitis C patients infected with HCV genotype-2 is a combination of pegylated interferon alfa and ribavirin over a 24 week period. It is unclear if a shorter treatment duration is possible for patients showing a rapid virological response (RVR) without compromising the sustained virologic response (SVR) in Korea. METHODS: 42 patients chronically infected with the HCV genotype-2 were treated with peginterferon alfa-2a 180 mcg/wk plus ribavirin 800 mg/d for 24 weeks and followed up for 24 weeks. The HCV RNA was qualitatively assessed after 4 weeks of treatment, and RVR was defined as undetectable HCV RNA at the 4th week. Retrospectively, 26 patients were treated with the standard treatment strategy (>/=80% of the intended duration and dosage), 14 patients with a short-term treatment strategy (<80% intended duration and dosage) and 2 patients were excluded. RESULTS: Among the 42 patients, 35 patients (83%) had RVR and 38 patients (90%) had a sustained virologic response (SVR). All 7 patients without RVR were treated with the standard treatment strategy, in whom 6 patients (86%) had SVR. Among the 35 patients with RVR, 14 patients were treated with short-term treatment and 19 patients were treated with the standard treatment. SVR was obtained in 12 out of the 14 patients (86%) in the short-term treatment group and 18 out of the 19 (95%) in the standard treatment group (P=0.373). CONCLUSION: HCV genotype-2 patients who have RVR with peginterferon and ribavirin treatment can be treated with a short-term treatment without compromising the chances for SVR. However, an additional trial will be needed to optimize the treatment duration.

Systematic Study of Functionalizable, Non-Biofouling Agarose Films with Protein and Cellular Patterns on Glass Slides.

Herein we demonstrate a systematic investigation of chemically functionalizable, non-biofouling agarose films over large-area glass surfaces. Agarose films, prepared with various concentrations of aqueous agarose, were activated by using periodate oxidation to generate aldehyde groups at the termini of the agarose chains. The non-biofouling efficacy and binding capabilities of the activated films were evaluated by using protein and cellular patterning, performed by using a microarrayer, microcontact printing, and micromolding in capillaries. Characterization by using a fluorescence slide scanner and a scanning-probe microscope revealed that the pore sizes of the agarose films played an important role in achieving desirable film performance; the 0.2 wt % agarose film exhibited the optimum efficacy in this work.

A computer-designed scaffold for bone regeneration within cranial defect using human dental pulp stem cells.

A computer-designed, solvent-free scaffold offer several potential advantages such as ease of customized manufacture and in vivo safety. In this work, we firstly used a computer-designed, solvent-free scaffold and human dental pulp stem cells (hDPSCs) to regenerate neo-bone within cranial bone defects. The hDPSCs expressed mesenchymal stem cell markers and served as an abundant source of stem cells with a high proliferation rate. In addition, hDPSCs showed a phenotype of differentiated osteoblasts in the presence of osteogenic factors (OF). We used solid freeform fabrication (SFF) with biodegradable polyesters (MPEG-(PLLA-co-PGA-co-PCL) (PLGC)) to fabricate a computer-designed scaffold. The SFF technology gave quick and reproducible results. To assess bone tissue engineering in vivo, the computer-designed, circular PLGC scaffold was implanted into a full-thickness cranial bone defect and monitored by micro-computed tomography (CT) and histology of the in vivo tissue-engineered bone. Neo-bone formation of more than 50% in both micro-CT and histology tests was observed at only PLGC scaffold with hDPSCs/OF. Furthermore, the PLGC scaffold gradually degraded, as evidenced by the fluorescent-labeled PLGC scaffold, which provides information to tract biodegradation of implanted PLGC scaffold. In conclusion, we confirmed neo-bone formation within a cranial bone defect using hDPSCs and a computer-designed PLGC scaffold.

Mussel-inspired, perfluorinated polydopamine for self-cleaning coating on various substrates.

We designed a perfluorinated dopamine derivative, which, upon oxidative polymerization, formed a structurally rough film of extremely low surface energy on various substrates. The static water contact angles larger than 150° and the low water sliding angles less than 7° confirmed the formation of superhydrophobic, self-cleaning surfaces.