Polymer structure-property requirements for stereolithographic 3D printing of soft tissue engineering scaffolds

Publication date: September 2017
Source:Biomaterials, Volume 140
Author(s): Ryan J. Mondschein, Akanksha Kanitkar, Christopher B. Williams, Scott S. Verbridge, Timothy E. Long
This review highlights the synthesis, properties, and advanced applications of synthetic and natural polymers 3D printed using stereolithography for soft tissue engineering applications. Soft tissue scaffolds are of great interest due to the number of musculoskeletal, cardiovascular, and connective tissue injuries and replacements humans face each year. Accurately replacing or repairing these tissues is challenging due to the variation in size, shape, and strength of different types of soft tissue. With advancing processing techniques such as stereolithography, control of scaffold resolution down to the μm scale is achievable along with the ability to customize each fabricated scaffold to match the targeted replacement tissue. Matching the advanced manufacturing technique to polymer properties as well as maintaining the proper chemical, biological, and mechanical properties for tissue replacement is extremely challenging. This review discusses the design of polymers with tailored structure, architecture, and functionality for stereolithography, while maintaining chemical, biological, and mechanical properties to mimic a broad range of soft tissue types.



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Investigation of itraconazole ternary amorphous solid dispersions based on povidone and Carbopol

Publication date: 30 August 2017
Source:European Journal of Pharmaceutical Sciences, Volume 106
Author(s): Fan Meng, Jordan Meckel, Feng Zhang
We investigate a ternary system that consists of itraconazole (ITZ) and two polymers: povidone K12 and Carbopol 907. The interactions between these two polymers and their effects on the properties of ternary ITZ amorphous solid dispersions (ASDs) are studied. These two polymers can form a water-insoluble complex in acidic aqueous media. The critical pH is determined to be 4.17. The weight percentage of Carbopol 907 in the interpolymer complex range from 59 to 70%, depending on the initial ratios between these two polymers in the starting solutions. This complexation is driven by a negative enthalpy change from the H-bonding between the two polymers and a positive entropy change from the freed water molecules. Due to the slow precipitation of the interpolymer complex in aqueous media, the attempt to prepare ternary ASD using solvent-controlled coprecipitation is not successful. Melt extrusion is identified to be the only viable method to prepare this ternary ASD. We find that interpolymer complex–based ASDs are physically less stable and demonstrate the poorest drug-release properties when compared to individual polymer-based binary ASDs. This study illustrates that the too strong interaction between polymers in ternary ASDs is detrimental to their performance.

Graphical abstract

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Influence of the drug distribution in electrospun gliadin fibers on drug-release behavior

Publication date: 30 August 2017
Source:European Journal of Pharmaceutical Sciences, Volume 106
Author(s): Ying Xu, Jiao-Jiao Li, Deng-Guang Yu, Gareth R. Williams, Jun-He Yang, Xia Wang
Drug distribution within its carrier in a solid dosage form often generates a profound influence on its release profile, particularly when the physicochemical properties of the carrier are exploited to manipulate drug release behavior. In this job, two different types of distributions of a model drug ibuprofen (IBU) within a protein gliadin in their electrospun nanofibers were intentionally created. One was homogeneous distribution in the monolithic fibers fabricated using a modified coaxial process, and the other one was heterogeneous distribution in the core/shell fibers prepared through a traditional coaxial process. SEM observations clearly demonstrated the different distributions of IBU within gliadin in the two kinds of nanofibers although both of them had smooth surfaces and linear morphology. XRD results showed that IBU was amorphously distributed in the monolithic fibers, but that some IBU crystalline lattices presented in the core/shell fibers. FTIR and RM spectra suggested that gliadin had good compatibility with IBU. In vitro dissolution tests verified that the gliadin nanofibers with a heterogeneous drug distribution could provide a better sustained release profile than its counterpart in terms of initial burst release and sustained release time period. Both the fiber formation and drug-controlled release mechanisms are suggested. The present study demonstrated a concept that drug distribution with the medicated nanomaterials can be exploited as a tool to optimize the drug sustained release profile.



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Improved anticancer effects of albumin-bound paclitaxel nanoparticle via augmentation of EPR effect and albumin-protein interactions using S-nitrosated human serum albumin dimer

Publication date: September 2017
Source:Biomaterials, Volume 140
Author(s): Ryo Kinoshita, Yu Ishima, Victor T.G. Chuang, Hideaki Nakamura, Jun Fang, Hiroshi Watanabe, Taro Shimizu, Keiichiro Okuhira, Tatsuhiro Ishida, Hiroshi Maeda, Masaki Otagiri, Toru Maruyama
In the latest trend of anticancer chemotherapy research, there were many macromolecular anticancer drugs developed based on enhanced permeability and retention (EPR) effect, such as albumin bound paclitaxel nanoparticle (nab- PTX, also called Abraxane^®). However, cancers with low vascular permeability posed a challenge for these EPR based therapeutic systems. Augmenting the intrinsic EPR effect with an intrinsic vascular modulator such as nitric oxide (NO) could be a promising strategy. S-nitrosated human serum albumin dimer (SNO-HSA Dimer) shown promising activity previously was evaluated for the synergistic effect when used as a pretreatment agent in nab-PTX therapy against various tumor models. In the high vascular permeability C26 murine colon cancer subcutaneous inoculation model, SNO-HSA Dimer enhanced tumor selectivity of nab-PTX, and attenuated myelosuppression. SNO-HSA Dimer also augmented the tumor growth inhibition of nab-PTX in low vascular permeability B16 murine melanoma subcutaneous inoculation model. Furthermore, nab-PTX therapy combined with SNO-HSA Dimer showed higher antitumor activity and improved survival rate of SUIT2 human pancreatic cancer orthotopic model. In conclusion, SNO-HSA Dimer could enhance the therapeutic effect of nab-PTX even in low vascular permeability or intractable pancreatic cancers. The possible underlying mechanisms of action of SNO-HSA Dimer were discussed.

Graphical abstract

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Low expression of long noncoding RNA CASC2 indicates a poor prognosis and promotes tumorigenesis in thyroid carcinoma

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Xiangqing Xiong, Hua Zhu, Xiangjian Chen
Recently, long noncoding RNAs (lncRNAs) have been shown to be linked to regulate different biological processes, such as cell growth, differentiation and tumorigenesis. LncRNAs have been identified to be promising clinical biomarkers in various tumors. Long noncoding RNAs cancer susceptibility candidate 2 (CASC2) has recently been demonstrated to be correlated to tumorigenesis in renal cell carcinoma, lung carcinoma, glioma, and gastric carcinoma. Nevertheless, the research on the biological function and clinical significance of CASC2 in thyroid carcinoma are still unclear. In this research, we focused on the relationship between CASC2 expression and clinicopathological factors in thyroid cancer. We found that the low expression of CASC2 correlated with multifocality and advanced tumor-node-metastasis (TNM) stage. Kaplan-Meier survival analysis and multivariate analysis showed that CASC2 expression may be an independent prognostic factor in human thyroid carcinoma. Moreover, the area under the receiver operating characteristic (ROC) curve of CASC2 indicated that its diagnostic value in thyroid carcinoma. Additionally, overexpression of CASC2 significantly inhibited the proliferation of thyroid carcinoma cells and arrested cell cycle at G0/G1 stage in thyroid cancer cells. Our findings showed that CASC2 may be a potential prognostic marker and therapeutic target.



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The impact of gut microbiota on kidney function and pathogenesis

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Fariba Mahmoodpoor, Yalda Rahbar Saadat, Abolfazl Barzegari, Mohammadreza Ardalan, Sepideh V Zununi Vahed
Chronic kidney diseases (CKDs) are a global health problem. Besides diverse leading reasons in initiation and progression of CKDs, it is evident that they might largely originate from changes in the gut microbial community (microbiota). Mounting evidence indicates that a bidirectional relationship exists between host and microbiome in humans and animals with CKDs. Changes in the microbiota composition and structure (dysbiosis) produce excessive amounts of uremic toxins (e.g. indoxyl sulfate, p-cresyl sulfate and trimethylamine-N-oxide) but less reno-protective metabolites that are implicated in oxidative stress, uremia, inflammation, deterioration of kidney function, kidney diseases progression, a higher prevalence of cardiovascular risk, and mortality in patients with CKD. The present review focuses on the pathogenic association between gut microbiota and kidney diseases like CKD, IgA nephropathy, and kidney stone disease. Certainly, novel insights into the impact of the gut microbiota in kidney diseases can be helpful to develop therapeutic strategies in order to avoid and/or treat aforementioned conditions.



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Pure total flavonoids from citrus improve non-alcoholic fatty liver disease by regulating TLR/CCL signaling pathway: A preliminary high-throughput ‘omics’ study

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Liyan Wu, Maoxiang Yan, Jianping Jiang, Beihui He, Wei Hong, Zhiyun Chen
ObjectiveThis study investigated the possible molecular mechanisms of pure total flavonoids from citrus (PTFC) for the treatment of non-alcoholic fatty liver disease (NAFLD) via toll-like receptor/C-C chemokine ligand (TLR/CCL) signaling pathways by monitoring the changes in gene expression profile in liver tissues induced by high-fat diet.MethodsWe performed systematical analyses on hepatic expression profiles of mRNAs in a high-fat diet (HFD)-induced steatotic animal model with or without PTFC treatment. The study was conducted by using MouseOneArray^® v2 gene chip, and analyzed by bioinformatics tools for differential gene expression. Real time-PCR, Western blot and liquid suspension array analysis were used to validate specific genes in the NAFLD liver expression profile in which PTFC plays a role in the TLR/CCR pathway.ResultsWe found that a total of 562 genes showed varying degrees of reversal after PTFC intervention. Pathway analysis of the differential gene expression in the HFD group and the normal diet group (ND group) revealed six signaling pathways related to inflammatory responses in the top ten results. Comparison of genes between the HFD+PTFC and the HFD groups indicated seven signaling pathways correlated with inflammatory response in the top ten results of the pathway analysis. The TLR/CCL inflammatory signaling pathways played an essential role during liver inflammation in NAFLD mice induced by high-fat diet. Real-time PCR, Western blot and liquid suspension array analysis of the differential gene expression involving the TLR/CCL signaling pathways validated the results of microarray detection.ConclusionPTFC may improve NAFLD by regulating TLR/CCL signaling pathways. Genomic studies provide additional evidence supporting the role of PTFC in the treatment of NAFLD.



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