Development and characterization of an amorphous curcumin-Eudragit®E100 solid dispersions with improved solubility, stability, and pharmacokinetic properties.

The development of amorphous solid dispersions (ASD) is one way to overcome the bioavailability challenges of poorly water-soluble drug. Herein, Curcumin (CUR) was dispersed in the polymeric matrix of Eudragit®E100 by solvent evaporation, giving ASD, donated as CUR@Eudragit®E100. Solubility and stability of CUR were greatly enhanced. DSC and XRD analysis confirmed that the incorporated CUR was present in an amorphous state. The interaction between CUR and Eudragit®E100 was investigated through FTIR and molecular modelling studies which implied that -OH groups in CUR, and carboxyl and amino groups in Eudragit®E100 involved in the hydrogen bond formation. High resolution atomic force microscopy was employed to directly visualize the molecular morphology of Eudragit®E100 and CUR in CUR@Eudragit®E100 and the interaction between CUR and the polymer. pH influenced CUR release profile in which the sustained release pattern was revealed vs the physical mixtures. From the plasma concentration vs time profile graph, oral bioavailability of Cur@Eudragit®E100 was approximately 5-fold higher than that of native CUR. These results confirmed the potential of designing ASD to enhance the solubility and bioavailability of CUR, simultaneously deliver CUR through this alternative administration route.

Dose Dependencies and Biocompatibility of Renal Clearable Gold Nanoparticles: From Mice to Non-human Primates.

While dose dependencies in pharmacokinetics and clearance are often observed in clinically used small molecules, very few studies have been dedicated to the understandings of potential dose-dependent in vivo transport of nanomedicines. Here we report that the pharmacokinetics and clearance of renal clearable gold nanoparticles (GS-AuNPs) are strongly dose-dependent once injection doses are above 15 mg kg-1 : high dose expedited the renal excretion and shortened the blood retention. As a result, the no-observed-adverse-effect-level (NOAEL) of GS-AuNPs was >1000 mg kg-1 in CD-1 mice. The efficient renal clearance and high compatibility can be translated to the non-human primates: no adverse effects were observed within 90 days after intravenous injection of 250 mg kg-1 GS-AuNPs. These fundamental understandings of dose effect on the in vivo transport of ultrasmall AuNPs open up a pathway to maximize their biomedical potentials and minimize their toxicity in the future clinical translation.

Three-dimensional bioprinting of tissue-engineered skin: Biomaterials, fabrication techniques, challenging difficulties, and future directions: A review.

As an emerging new manufacturing technology, Three-dimensional (3D) bioprinting provides the potential for the biomimetic construction of multifaceted and intricate architectures of functional integument, particularly functional biomimetic dermal structures inclusive of cutaneous appendages. Although the tissue-engineered skin with complete biological activity and physiological functions is still cannot be manufactured, it is believed that with the advances in matrix materials, molding process, and biotechnology, a new generation of physiologically active skin will be born in the future. In pursuit of furnishing readers and researchers involved in relevant research to have a systematic and comprehensive understanding of 3D printed tissue-engineered skin, this paper furnishes an exegesis on the prevailing research landscape, formidable obstacles, and forthcoming trajectories within the sphere of tissue-engineered skin, including: (1) the prevalent biomaterials (collagen, chitosan, agarose, alginate, etc.) routinely employed in tissue-engineered skin, and a discerning analysis and comparison of their respective merits, demerits, and inherent characteristics; (2) the underlying principles and distinguishing attributes of various current printing methodologies utilized in tissue-engineered skin fabrication; (3) the present research status and progression in the realm of tissue-engineered biomimetic skin; (4) meticulous scrutiny and summation of the extant research underpinning tissue-engineered skin inform the identification of prevailing challenges and issues.

Circulating miRNAs as Epigenetic Mediators of Periodontitis and Preeclampsia Association.

Objective: Periodontal disease has been associated with pregnancy complications including preeclampsia. This bioinformatic study is aimed at investigating the possible role of circulating microRNAs (miRNAs) as mediators of the association between maternal periodontal disease and preeclampsia. Methods: Peripheral blood miRNA profiles of periodontitis and controls were sought from Gene Expression Omnibus (GEO), and differential expression analysis was performed. Experimentally validated circulating miRNAs associated with preeclampsia were determined from the Human MicroRNA Disease Database (HMDD v3.0). Venn diagrams were drawn to identify shared circulating differential miRNAs (DEmiRNAs). Significantly enriched target genes, KEGG pathways, and Gene Ontology (GO) terms for the set of shared DEmiRNA were predicted using miRNA enrichment analysis and annotation tool (miEAA v 2.0). Additionally, the shared DEmiRNA-enriched target genes were analyzed for enriched WikiPathways, BioCarta metabolic pathways, and tissue proteins in the human proteome map. Results: Among 183 circulating DEmiRNA in periodontitis and 60 experimentally validated miRNA in preeclampsia, 9 shared DEmiRNA were identified. The top among 32 overrepresented target genes included MAFB, PSAP, and CDK5RAP2, top among 14 enriched KEGG pathways were renin-angiotensin system and graft-versus-host disease, and that among enriched 44 GO profiles included "positive regulation of epidermal growth factor-activated receptor activity" and "sequestering of calcium ion." In the overrepresented target gene set, among 10 enriched WikiPathways, the top included "NAD metabolism, sirtuins, and aging" and "regulation of Wnt/B-catenin signaling by small molecule compounds" and PPAR-related mechanisms was top among 13 enriched BioCarta metabolic pathways. Conclusion: A circulating 9-DEmiRNA set was significantly linked to both periodontitis and preeclampsia. Enrichment analysis identified specific genes, pathways, and functional mechanisms, which may be epigenetically altered and thereby mediate the biological association of periodontitis and preeclampsia.

Fracture Behavior and Digital Image Analysis of GFRP Reinforced Concrete Notched Beams.

This study presents three-point bending fracture tests on glass fiber-reinforced polymer (GFRP) reinforced concrete notched beams. Few studies have been conducted to date to understand the fracture behavior of this type of specimens. The specimens have nominal depth, width, and length equal to 150 mm, 150 mm, and 550 mm. Plain concrete notched beams with the same dimensions are cast from the same batch of concrete to compare the responses with GFRP reinforced concrete notched beams. The notch of the plain concrete specimens is either saw cut or cast. These two notch fabrication methods are compared based on the load responses. The peak load, crack mouth opening displacement (CMOD), GFRP bar slip at two ends, and load point displacement are used to discuss the results of the fracture tests. In addition, digital image analysis is performed to identify the fracture process zone (FPZ) and the location of the neutral axis, which are used to determine the force in the GFRP bar via cross-sectional analysis. Finally, the GFRP bar force versus slip responses are compared with those from the pull-out tests performed on the same bar to show that the bond of the bar in the pull-out tests represents an upper bound limit compared to the behavior in bending.

Highly Ordered, Plasmonic Enhanced Inverse Opal Photonic Crystal for Ultrasensitive Detection of Staphylococcal Enterotoxin B.

Although there is considerable interest in self-assembly of ordered, porous "inverse opal" structures for optical, electronic, and chemical applications, uncontrolled defect formation limits the usefulness of such materials. Herein, we develop a highly ordered and plasmonic enhanced sensing inverse opal photonic crystal (IOPC) material. The co-assembly of the colloidal template with the matrix material avoids the need for liquid penetration into the preassembled colloidal crystals and minimizes the associated rupture and inhomogeneity of the resulting IOPC. Au nanoparticles (Au NPs) not only act as a "bridge" between recognition elements (aptamers) and IOPCs, but also can amplify optical signals. Furthermore, the enhancement mechanism of Au NPs is simulated by COMSOL. During the detection process, the optical signal of the sensing Au-Apt IOPC responds to the Staphylococcal enterotoxin B with a concentration ranging from 10-2 to 103 pg mL-1, and the limit of detection is 2.820 fg mL-1. Spiked real sample detection indicates that the as-proposed method possessed good accuracy. The sensing Au-Apt IOPC provides an extensive biosensor platform to detect a variety of toxic and harmful substances through replacing the aptamer by other recognition elements, such as antibodies or receptors.