Long-Term Sustained Release of Salicylic Acid from Cross-Linked Biodegradable Polyester Induces a Reduced Foreign Body Response in Mice

There has been a continuous surge toward developing new biopolymers that exhibit better in vivo biocompatibility properties in terms of demonstrating a reduced foreign body response (FBR). One approach to mitigate the undesired FBR is to develop an implant capable of releasing anti-inflammatory molecules in a sustained manner over a long time period. Implants causing inflammation are also more susceptible to infection. In this article, the in vivo biocompatibility of a novel, biodegradable salicylic acid releasing polyester (SAP) has been investigated by subcutaneous implantation in a mouse model. The tissue response to SAP was compared with that of a widely used biodegradable polymer, poly(lactic acid-co-glycolic acid) (PLGA), as a control over three time points: 2, 4, and 16 weeks postimplantation. A long-term in vitro study illustrates a continuous, linear (zero order) release of salicylic acid with a cumulative mass percent release rate of 7.34 x 10(-4) h(-1) over similar to 1.5-17 months. On the basis of physicochemical analysis, surface erosion for SAP and bulk erosion for PLGA have been confirmed as their dominant degradation modes in vivo. On the basis of the histomorphometrical analysis of inflammatory cell densities and collagen distribution as well as quantification of proinflammatory cytokine levels (TNF-alpha and IL-1 beta), a reduced foreign body response toward SAP with respect to that generated by PLGA has been unambiguously established. The favorable in vivo tissue response to SAP, as manifest from the uniform and well-vascularized encapsulation around the implant, is consistent with the decrease in inflammatory cell density and increase in angiogenesis with time. The above observations, together with the demonstration of long-term and sustained release of salicylic acid, establish the potential use of SAP for applications in improved matrices for tissue engineering and chronic wound healing.

Validation of polyvinylidene fluoride nasal sensor to assess nasal obstruction in comparison with subjective technique

Objective: The aim of this study is to validate the applicability of the PolyVinyliDene Fluoride (PVDF) nasal sensor to assess the nasal airflow, in healthy subjects and patients with nasal obstruction and to correlate the results with the score of Visual Analogue Scale (VAS). Methods: PVDF nasal sensor and VAS measurements were carried out in 50 subjects (25-healthy subjects and 25 patients). The VAS score of nasal obstruction and peak-to-peak amplitude (Vp-p) of nasal cycle measured by PVDF nasal sensors were analyzed for right nostril (RN) and left nostril (LN) in both the groups. Spearman's rho correlation was calculated. The relationship between PVDF nasal sensor measurements and severity of nasal obstruction (VAS score) were assessed by ANOVA. Results: In healthy group, the measurement of nasal airflow by PVDF nasal sensor for RN and LN were found to be 51.14 +/- 5.87% and 48.85 +/- 5.87%, respectively. In patient group, PVDF nasal sensor indicated lesser nasal airflow in the blocked nostrils (RN: 23.33 +/- 10.54% and LN: 32.24 +/- 11.54%). Moderate correlation was observed in healthy group (r = 0.710, p < 0.001 for RN and r = 0.651, p < 0.001 for LN), and moderate to strong correlation in patient group (r = 0.751, p < 0.01 for RN and r = 0.885, p < 0.0001 for LN). Conclusion: PVDF nasal sensor method is a newly developed technique for measuring the nasal airflow. Moderate to strong correlation was observed between PVDF nasal sensor data and VAS scores for nasal obstruction. In our present study, PVDF nasal sensor technique successfully differentiated between healthy subjects and patients with nasal obstruction. Additionally, it can also assess severity of nasal obstruction in comparison with VAS. Thus, we propose that the PVDF nasal sensor technique could be used as a new diagnostic method to evaluate nasal obstruction in routine clinical practice. (C) 2015 Elsevier Inc. All rights reserved.

Polyvinylidene fluoride based lightweight and corrosion resistant electromagnetic shielding materials

Various NixCo1-x alloys (with x varying from 0-60 wt%, Ni: nickel, Co: cobalt) were prepared by vacuum arc melting and mixed with polyvinylidene fluoride (PVDF) to design lightweight, flexible and corrosion resistant materials that can attenuate electromagnetic radiation. The saturation magnetization scaled with the fraction of Co in the alloy. Two key properties such as high-magnetic permeability and high-electrical conductivity were targeted. While the former was achieved using a Ni-Co alloy, multiwalled carbon nanotubes (CNTs) in the composites accomplished the latter. A unique approach was adopted to prepare the composites wherein PVDF powder along with CNTs and Ni-Co flakes were made into a paste, using a solvent, followed by hot pressing. Interestingly, CNTs facilitated in uniform dispersion of the Ni-Co alloy in PVDF, as manifested from synergistic improvement in the electrical conductivity. A significant improvement in the shielding effectiveness (41 dB, >99.99% attenuation) was achieved with the addition of 50 wt% of Ni40Co60 alloy and 3 wt% CNTs. Intriguingly, due to the unique processing technique adopted here, the flexibility of the composites was retained and more interestingly, the composites were resistant to corrosion as compared to only Ni-Co alloy.

Panchromatic Borane-aza-BODIPY Conjugate: Synthesis, Intriguing Optical Properties, and Selective Fluorescent Sensing of Fluoride Anions

A new triarylborane-aza-BODIPY conjugate is reported. The compound consists of two blue emissive dimesitylarylborane moieties and a near-infrared (NIR) emissive aza-BOIDPY core and shows panchromatic absorption spanning approximately 300-800 nm. DFT computational studies suggest limited electronic communication between the individual fluorophore units. Hence, the partial energy transfer from blue fluorophore triarylborane to NIR chromophore aza-BODIPY unit leads to a broad dual-emissive feature covering a large part of visible and NIR region. Furthermore, the broadband emissive compound can act as a selective sensor for fluoride anion as a result of fluorescence quenching response in both visible and NIR spectral regions.

Photonic monitoring of chitosan nanostructured alginate microcapsules for drug release

By using a novel microfluidic set-up for drug screening applications, this study examines delivery of a novel risedronate based drug formulation for treatment of osteoporosis that was developed to overcome the usual shortcomings of risedronate, such as its low bioavailability and adverse gastric effects. Risedronate nanoparticles were prepared using muco-adhesive polymers such as chitosan as matrix for improving the intestinal cellular absorption of risedronate and also using a gastric-resistant polymer such as sodium alginate for reducing the gastric inflammation of risedronate. The in-vitro characteristics of the alginate encapsulated chitosan nanoparticles are investigated, including their stability, muco-adhesiveness, and Caco-2 cell permeability. Fluorescent markers are tagged with the polymers and their morphology within the microcapsules is imaged at various stages of drug release.

Estimate of N2O release from pit-toilets

The use of pit-toilets has severely contaminated the groundwater with nitrate ions in Mulbagal town, Karnataka, India. This paper examines the potential of nitrate ions in the pit-toilet effluents to transform to N2O and to escape to atmosphere from 16 wards of Mulbagal town. Anaerobic conditions prevailing in the pit-toilet convert 25 % of the available N to ammonium ions. Only 3-33 % of ammonium ions transform to nitrate ions in the pit-toilet and escape with the effluent. During migration to aquifer, only 4.5 % of available nitrate concentration in the effluent transforms to N-2 and N2O gases in the 1.5-m-thick saturated zone underlying the pit-toilet; 36-55 % of the gases comprise N2O and the remainder of N-2. Further only 18 % of N2O formed escapes to atmosphere, while the remainder is retained in soil solution. Calculations show that 9.88 x 10(13) molecules of N2O/cm(2) would be cumulatively released from 16 wards of Mulbagal town, over an area of 4.9 km(2).

Contrasting Effects of Graphene Oxide and Poly(ethylenimine) on the Polymorphism in Poly(vinylidene fluoride)

The nature of interaction between a heteronucleating agent (graphene oxide, GO) and a strongly polar macromolecule (poly(ethylenimine), PEI) with poly(vinylidene fluoride) (PVDF) influencing the crystalline structure and morphology has been systematically investigated in this work. PEI interacts with PVDF via ion-dipole interaction, which helps in lowering the free energy barrier for nucleation thereby promoting faster crystallization. In contrast, besides interacting with PVDF, GO also promotes heteronucleation in PVDF. We observed that both GO and PEI have very different effects on the overall crystalline morphology of PVDF. For instance, the neat PVDF showed a mixture of both alpha and beta phases when cooled from the melt. However, incorporation of 0.1 wt % GO resulted in phase transformation from the stable alpha-phase to polar beta-polymorph in PVDF. In contrast, PEI, which also resulted in faster crystallization in PVDF predominantly, resulted in the stable alpha- phase. Various techniques like Fourier transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry were employed to confirm the phase transformations in PVDF. PEI was further grafted onto GO nanosheets to understand the combined effects of both GO and PEI on the polymorphism in PVDF. The PVDF/PEI-GO composite showed a mixture of phases, predominantly rich in a. These phenomenal effects were further analyzed and corroborated with the specific interaction between GO and PEI with PVDF using X-ray photon scattering (XPS) and NMR. In addition, the dielectric permittivity increased significantly in the presence of GO and PEI in the composites. For instance, PVDF/PEI-GO showed the highest permittivity of 39 at 100 Hz.

Controlled Release of Salicylic Acid from Biodegradable Cross-Linked Polyesters

The purpose of this work was to develop a family of crosslinked poly(xylitol adipate salicylate)s with a wide range of tunable release properties for delivering pharmacologically active salicylic acid. The synthesis parameters and release conditions were varied to modulate polyester properties and to understand the mechanism of release. Varying release rates were obtained upon longer curing (35% in the noncured polymer to 10% in the cured polymer in 7 days). Differential salicylic acid loading led to the synthesis of polymers with variable cross-linking and the release could be tuned (100% release for the lowest loading to 30% in the highest loading). Controlled release was monitored by changing various factors, and the release profiles were dependent on the stoichiometric composition, pH, curing time, and presence of enzyme. The polymer released a combination of salicylic acid and disalicylic acid, and the released products were found to be nontoxic. Minimal hemolysis and platelet activation indicated good blood compatibility. These polymers qualify as ``bioactive'' and ``resorbable'' and can, therefore, find applications as immunomodulatory resorbable biomaterials with tunable release properties.

Glioblastoma-derived Macrophage Colony-stimulating Factor (MCSF) Induces Microglial Release of Insulin-like Growth Factor-binding Protein 1 (IGFBP1) to Promote Angiogenesis

Glioblastoma (grade IV glioma/GBM) is the most common primary adult malignant brain tumor with poor prognosis. To characterize molecular determinants of tumor-stroma interaction in GBM, we profiled 48 serum cytokines and identified macrophage colony-stimulating factor (MCSF) as one of the elevated cytokines in sera from GBM patients. Both MCSF transcript and protein were up-regulated in GBM tissue samples through a spleen tyrosine kinase (SYK)-dependent activation of the PI3K-NF kappa B pathway. Ectopic overexpression and silencing experiments revealed that glioma-secreted MCSF has no role in autocrine functions and M2 polarization of macrophages. In contrast, silencing expression of MCSF in glioma cells prevented tube formation of human umbilical vein endothelial cells elicited by the supernatant from monocytes/microglial cells treated with conditioned medium from glioma cells. Quantitative proteomics based on stable isotope labeling by amino acids in cell culture showed that glioma-derived MCSF induces changes in microglial secretome and identified insulin-like growth factor-binding protein 1 (IGFBP1) as one of the MCSF-regulated proteins secreted by microglia. Silencing IGFBP1 expression in microglial cells or its neutralization by an antibody reduced the ability of supernatants derived from microglial cells treated with glioma cell-conditioned medium to induce angiogenesis. In conclusion, this study shows up-regulation of MCSF in GBM via a SYK-PI3K-NF kappa B-dependent mechanism and identifies IGFBP1 released by microglial cells as a novel mediator of MCSF-induced angiogenesis, of potential interest for developing targeted therapy to prevent GBM progression.

Controlled release kinetics of p-aminosalicylic acid from biodegradable crosslinked polyesters for enhanced anti-mycobacterial activity

Unlike conventional polymeric drug delivery systems, where drugs are entrapped in polymers, this study focuses on the incorporation of the drug into the polymer backbone to achieve higher loading and sustained release. Crosslinked, biodegradable, xylitol based polyesters have been synthesized in this study. The bioactive drug moiety, p-aminosalicylic acid (PAS), was incorporated in xylitol based polyesters to impart its anti-mycobacterial activity. To understand the influence of the monomer chemistry on the incorporation of PAS and its subsequent release from the polymer, different diacids have been used. Controlled release profiles of the drug from these polyesters were studied under normal physiological conditions. The degradation of the polyesters varied from 48% to 76% and the release of PAS ranged from 54% to 65% of its initial loading in 7 days. A new model was developed to explain the release kinetics of PAS from the polymer that accounted for the polymer degradation and drug concentration. The thermal, mechanical, drug release and cytocompatibility properties of the polymers indicate their suitability in biomedical applications. The released products from these polymers were observed to be pharmacologically active against Mycobacteria. The high drug loading and sustained release also ensured enhanced efficacy. These polymers form biocompatible, biodegradable polyesters where the sustained release of PAS may be tailored for potential treatment of mycobacterial infections. Statement of significance In the present work, we report on novel polyesters with p-aminosalicylic acid (PAS) incorporated in the polymer backbone. The current work aims to achieve controlled release of PAS and ensures the delivered PAS is stable and pharmacologically active. The novelty of this work primarily involves the synthetic chemistry of polymerization and detailed analysis and efficacy of active PAS delivery. A new kinetic model has been developed to explain the PAS release profiles. These polymers are biodegradable, cytocompatible and anti-mycobacterial in nature. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Physical insights into salicylic acid release from poly(anhydrides)

Salicylic acid (SA) based biodegradable polyanhydrides (PAHs) are of great interest for drug delivery in a variety of diseases and disorders owing to the multi-utility of SA. There is a need for the design of SA-based PAHs for tunable drug release, optimized for the treatment of different diseases. In this study, we devised a simple strategy for tuning the release properties and erosion kinetics of a family of PAHs. PAHs incorporating SA were derived from related aliphatic diacids, varying only in the chain length, and prepared by simple melt condensation polymerization. Upon hydrolysis induced erosion, the polymer degrades into cytocompatible products, including the incorporated bioactive SA and diacid. The degradation follows first order kinetics with the rate constant varying by nearly 25 times between the PAH obtained with adipic acid and that with dodecanedioic acid. The release profiles have been tailored from 100% to 50% SA release in 7 days across the different PAHs. The release rate constants of these semi-crystalline, surface eroding PAHs decreased almost linearly with an increase in the diacid chain length, and varied by nearly 40 times between adipic acid and dodecanedioic acid PAH. The degradation products with SA concentration in the range of 30-350 ppm were used to assess cytocompatibility and showed no cytotoxicity to HeLa cells. This particular strategy is expected to (a) enable synthesis of application specific PAHs with tunable erosion and release profiles; (b) encompass a large number of drugs that may be incorporated into the PAH matrix. Such a strategy can potentially be extended to the controlled release of other drugs that may be incorporated into the PAH backbone and has important implications for the rational design of drug eluting bioactive polymers.