Investigating the in-vitro bioactivity, biodegradability and drug release behavior of the newly developed PES/HA/WS biocompatible nanocomposites as bone graft substitute.

The nucleation of carbonate-containing apatite on the biomaterials surface is regarded as a significant stage in bone healing process. In this regard, composites contained hydroxyapatite (Ca10(PO4)6(OH)2, HA), wollastonite (CaSiO3, WS) and polyethersulfone (PES) were synthesized via a simple solvent casting technique. The in-vitro bioactivity of the prepared composite films with different weight ratios of HA and WS was studied by placing the samples in the simulated body fluid (SBF) for 21 days. The results indicated that the the surface of composites containing 2 wt% HA and 4 wt% WS was completely covered by a thick bone-like apatite layer, which was characterized by Grazing incidence X-ray diffraction, attenuated total reflectance-Fourier transform infrared spectrometer, field emission electron microscopy and energy dispersive X-ray analyzer (EDX). The degradation study of the samples showed that the concentration of inorganic particles could not influence the degradability of the polymeric matrix, where all samples expressed similar dexamethasone (DEX) release behavior. Moreover, the in-vitro cytotoxicity results indicated the significant cyto-compatibility of all specimens. Therefore, these findings revealed that the prepared composite films composed of PES, HA, WS and DEX could be regarded as promising bioactive candidates with low degradation rate for bone tissue engineering applications.

Low temperature preparation of diopside nanoparticles: in-vitro bioactivity and drug loading evaluation.

Bioactive diopside (CaMgSi2O6) nanoparticles have recently gained potential usefulness as bone replacement materials and nano vehicles for delivering therapeutics. The structural characteristics of this ceramic have found to be a key factor in bone bonding ability. To attain the desired product for 100% clinical success, it is important to realize the relationship between structure and biological activity. Synthesis of these nanoparticles via the solid-state method has been regarded as a low-cost and easy process in large-scale, but time consuming reactions and high temperature (≈ 1400 °C) are required. On the other side, the wet chemistry can overcome these drawbacks, whereas the presence of byproducts in the final powder has limited this method in large-scale production. The present document has represented a simple, fast and one-pot sol-gel approach for the synthesis of highly pure diopside nano-powders (< 20 nm) by using not-expensive precursors. Calcination of the obtained powder has been conducted at various temperatures (700, 1000 and 1200 °C). The physicochemical and microstructural properties of the products have been characterized by XRD, FTIR, FESEM and TEM. Moreover, the impact of the crystallinity on the bioactivity, drug loading capacity and drug release behavior of the synthesized nanoparticles have been investigated here for the first time. The in-vitro bioactivity results of the prepared diopside samples in a simulated body fluid (SBF) at 37 °C revealed the higher capability of the sintered sample to deposit calcium phosphate, compared with the amorphous one. High quantity of gentamicin (around 10 µg) could attach to the surface of 1 miligram of the sintered diopside during the early stages of contact (3 h), suggesting the potential use of diopside as a new class of nano-vehicles for antibiotics. The release behavior indicated a sustained release of gentamicin (80%) after 24 h. In conclusion, diopside nanoparticles can be a promising candidate as a drug-vehicle for bone filling, implant coating or bone cement applications.

Investigating the antibacterial activity of carboxymethyl cellulose films treated with novel Ag@GO decorated SiO2 nanohybrids.

Emergence of drug-resistant bacteria has raised the interest of employing antimicrobial biomaterials for acute wound treatment. This study aimed at preparing novel antibacterial CMC films containing different proportions of silica and graphene oxide/silver nanohybrids. The synthesis of high-purity SiO2 particles was performed by the reaction of neutralization of sodium silicate solution with HCl solution and characterized by XRD, FTIR, FE-SEM, EDS and ICP. Sonochemical method was utilized to fabricate Ag@GO nanohybrid. Different proportions of the synthesized SiO2 were incorporated into the Ag@GO nanohybrid via a simple precipitation method to obtain Ag@GO-SiO2 particles, which were then analyzed by XRD, FTIR, FE-SEM and EDS. Finally, the in-vitro antibacterial examination via disk diffusion and optical density methods indicated the effective antimicrobial activities of the films towards E. coli, P. aeruginosa and S. aureus. These findings expressed the ability of the obtained novel films in protecting wound from pathogenic microbial infections.

Development of bioactive sodium alginate/sulfonated polyether ether ketone/hydroxyapatite nanocomposites: Synthesis and in-vitro studies.

Developing bioactive composites to fill bone cavities caused by disease, injury or surgery still remains a challenge. The aim of this research was to develop a new nanostructured sodium alginate/sulfonated polyether ether ketone/nano-hydroxyapatite (Alg/SPEEK/HA) biocomposite via a simple chemical precipitation strategy. Structural analysis was carried out using X-ray diffraction (XRD), Fourier transformation infrared spectroscopy (FTIR). Thermogravimetric analysis (TGA) was used to compare the HA content of the composites. The in-vitro bioactivity of the composites with different content of HA was investigated by immersing the specimens in the simulated body fluid (SBF) for 15 days. The presence of HA in the composite structure gave rise to the precipitation of an apatite layer on the surface, which was increased by increase in the content of HA. The formation of the HA layer on the composite surface was scrutinized via FESEM and EDX analysis. Transmission electron microscopy (TEM) images exhibited the presence of HA nanoparticles with less than 30 nm in size. The in-vitro cytotoxicity evaluation was also carried out using MG-63 cells via the MTT assay, which revealed that the cytocompatibility of all specimens was increased with raising the HA content. However, the higher concentration (100 µg/ml) of the composites displayed some toxicity against MG-63 cells. These findings, therefore, proposed that the achieved novel nanocomposites could be regarded as promising materials to serve as bone filler.

Preparation and in-vitro evaluation of ß-CD/HA nanocomposite as a potential carrier for hydrophobic drugs.

This study aimed to provide a new drug delivery system for hydrophobic compounds. Dexamethasone (DEX) was employed as a hydrophobic model drug, which incorporated into the network of hydroxyapatite (HA)/Cyclodextrin (ß-CD) nanocomposite. Phase analysis, chemical bonding, morphology, and drug release was evaluated using XRD, FTIR, FESEM, and UV-vis spectroscopy, respectively. XRD patterns showed the formation of the crystalline structure and FTIR analysis showed the chemical bonding between organic and inorganic phases. FESEM images accompanied by EDX analysis confirmed the presence of HA nano-flakes. Release of DEX loaded ß-CD/HA was measured to be around 4.6% and 18.7% in pH5.3 and pH 7.4, respectively. In conclusion, the prepared system could be a potential pH sensitive carrier for sustainable release of water-insoluble drugs.

Self-emulsifying drug delivery systems changing their zeta potential via a flip-flop mechanism.

To overcome the mucus layer and cell membrane barrier, self-emulsifying drug delivery systems (SEDDS) exhibiting negative zeta potential, switching to positive values when having reached the cell membrane is a promising approach. Accordingly, a novel conjugate was synthesized by covalent attachment of phosphotyrosine to octadecylamine, which was incorporated into SEDDS. Generated system presented an average diameter of 32 nm and zeta potential of around -12 mV when being diluted 1:100 in 100 mM HEPES buffer pH 7.5 containing 5 mM MgCl2 and 0.2 mM ZnCl2. Incubation of SEDDS with isolated intestinal alkaline phosphatase (IAP) resulting in enzymatic cleavage of phosphate ester moiety caused a shift in zeta potential up to +5.3 mV. As non-toxicity of the developed SEDDS diluted 1:1000 in 25 mM HEPES buffer pH 7.5 containing 5% glucose was observed on Caco-2 cells by employing resazurin assay, this system may provide an inspiring strategy for future zeta potential changing drug delivery systems to master the mucus and membrane barrier.

Anti-thrombogenicity and permeability of polyethersulfone hollow fiber membrane with sulfonated alginate toward blood purification.

The main aim of this study was to evaluate the suitability of sulfonated alginate as a modifying agent to enhance the hemocompatibility of self-fabricated polyethersulfone (PES) hollow fiber membrane for blood detoxification. Sodium alginate was sulfonated with a degree of 0.6 and immobilized on the membrane via surface amination and using glutaraldehyde as cross-linking agent. Coating layer not only improved the membrane surface hydrophilicity, but also induced -39.2 mV negative charges on the surface. Water permeability of the modified membrane was enhanced from 67 to 95 L/m2·h·bar and flux recovery ratio increased more than 2-fold. Furthermore, the modified membrane presented higher platelet adhesion resistance (reduced by more than 90%) and prolonged coagulation time (35 s for APTT and 14 s for PT) in comparison with the pristine PES hollow fiber membrane, which verified the improved anti-thrombogenicity of the modified membrane. On the other hand, obtained membrane after 3 h coating could remove up-to 60% of the uremic toxins. According to the obtained data, sulfonated alginate can be a promising modifying agent for the future blood-contacting membrane and specially blood purification issues.