In this study, the novel biomimetic aerogel-based composite scaffolds through a synergistic combination of wet chemical synthesis and advanced engineering approaches have successfully designed. To this aim, initially the photo-crosslinkable methacrylated silk fibroin (SF-MA) biopolymer and methacrylated hollow mesoporous silica microcapsules (HMSC-MA) as the main constituents of the novel composite aerogels were synthesized. Afterward, by incorporation of drug-loaded HMSC-MA into the self-assembled SF-MA, printable gel-based composite inks are developed. By exploiting micro-extrusion-based three-dimensional (3D) printing, SF-MA-HMSC composite gels are printed by careful controlling their viscosity to provide a means to control the shape fidelity of the resulted printed gel constructs. The developed scaffold has shown a multitude of interesting biophysical and biological performances. Namely, thanks to the photo-crosslinking of the gel components during the 3D printing, the scaffolds become mechanically more stable than the pristine SF scaffolds. Also, freeze-casting the printed constructs generates further interconnectivity in the printed pore struts resulting in the scaffolds with hierarchically organized porosities necessary for cell infiltration and growth. Importantly, HMSC incorporated scaffolds promote antibacterial drug delivery, cellular ingrowth and proliferation, promoting osteoblastic differentiation by inducing the expression of osteogenic markers and matrix mineralization. Finally, the osteoconductive, -inductive, and anti-infective composite aerogels are expected to act as excellent bone implanting materials with an extra feature of local and sustained release of drug for efficient therapy of bone-related diseases.
Hollow mesoporous silica capsules were used as amphiphilic drug delivery vehicles and sustained release systems for antimicrobial and anticancer drugs.
The coronavirus disease-19 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has taken the world by surprise. To date, a worldwide approved treatment remains lacking and hence in the context of rapid viral spread and the growing need for rapid action, drug repurposing has emerged as one of the frontline strategies in the battle against SARS-CoV2. Repurposed drugs currently being evaluated against COVID-19 either tackle the replication and spread of SARS-CoV2 or they aim at controlling hyper-inflammation and the rampaged immune response in severe disease. In both cases, the target for such drugs resides in the lungs, at least during the period where treatment could still provide substantial clinical benefit to the patient. Yet, most of these drugs are administered systemically, questioning the percentage of administered drug that actually reaches the lung and as a consequence, the distribution of the remainder of the dose to off target sites. Inhalation therapy should allow higher concentrations of the drug in the lungs and lower concentrations systemically, hence providing a stronger, more localized action, with reduced adverse effects. Therefore, the nano-reformulation of the repurposed drugs for inhalation is a promising approach for targeted drug delivery to lungs. In this review, we critically analyze, what nanomedicine could and ought to do in the battle against SARS-CoV2. We start by a brief description of SARS-CoV2 structure and pathogenicity and move on to discuss the current limitations of repurposed antiviral and immune-modulating drugs that are being clinically investigated against COVID-19. This account focuses on how nanomedicine could address limitations of current therapeutics, enhancing the efficacy, specificity and safety of such drugs. With the appearance of new variants of SARS-CoV2 and the potential implication on the efficacy of vaccines and diagnostics, the presence of an effective therapeutic solution is inevitable and could be potentially achieved via nano-reformulation. The presence of an inhaled nano-platform capable of delivering antiviral or immunomodulatory drugs should be available as part of the repertoire in the fight against current and future outbreaks.
In order to develop new sustainable and reusable concepts for the degradation of omnipresent industrial plastics, immobilization of (bio)catalysts on nanocarriers offers unique opportunities for selective depolymerization and catalyst recovery. In this study, enzymes (lipase and cutinase) were covalently immobilized on carrier nanoparticles (SiO2 and Fe3O4@SiO2) through 3-(aminopropyl)trimethoxysilane and glutaraldehyde linkers forming a stable bond to enzyme molecules. The presence of enzymes on the surface was confirmed by zeta potential and XPS measurements, while their degradation activity and long-term stability of up to 144 h was demonstrated by the conversion of 4-nitrophenyl acetate to 4-nitrophenol. Furthermore, enzymatic decomposition (hydrolysis/oxidation) of electrospun polycaprolactone fiber mats was verified through morphological (SEM) and weight loss studies, which evidently showed a change in the fiber morphology due to enzymatic degradation and accordingly a weight loss. Graphic abstract
Intensive and overuse of antibiotics during the last years has triggered a distinct rise in antibiotic resistance worldwide. In addition to the newly developed antimicrobials, there is a high demand for alternative treatment options against persistent bacterial infections. The biocidal impact of transition metal ions like copper (Cu 2+ ), silver (Ag + ), and zinc (Zn 2+ ) also known as oligodynamic effect has been used through ages to kill or inhibit the growth of microorganisms and to employ long-term prevention strategies against their biological antagonists. Herein, we report on the synthesis of Cu, Ag and Zn metal Accepted ArticleThis article is protected by copyright. All rights reserved and corresponding oxide nanoparticles immobilized on hollow mesoporous silica capsules (HMSCs) obtained by a hard-template assisted sol-gel synthesis followed by reduction of appropriate metal salts in the presence of HMSCs. Compartmentalization of nanosized metal and oxide clusters in Ag@HMSCs, Cu@HMSCs and ZnO@HMSCs particles prevented their agglomeration and offered a high release kinetics of metal ions between 2.0-3.7 mM during 24 hours, as monitored by UV-vis analyses. The distribution and morphology of pristine and metal functionalized HMSCs was evaluated by transmission electron microscopy (TEM) analysis revealing the successful synthesis of Ag, Cu and ZnO nanoparticles supported on HMSCs. X-ray photoelectron spectroscopy (XPS) revealed that mainly Cu(II), Ag(0) and Zn(II) species were present in the modified HMSCs. In addition to the surface attachment of preformed metal (Ag and Cu) and metal oxide (ZnO) cluster, nucleation of metal nanoparticles inside the void of HMSCs provided an internal reservoir which allowed for a time-dependent release of metal ions through slower dissolution rates leading to a long-term and sustained bacterial inhibition over several hours. The high antimicrobial efficiency of Ag@HMSCs, Cu@HMSCs, and ZnO@HMSCs particles was investigated towards both Grampositive (B. subtilis) and Gram-negative (E. coli) bacteria by INT assays showing a complete growth inhibition for both bacteria types after 24 hours. While Ag@HMSCs and Cu@HMSCs showed a higher susceptibility against Gram-negative bacteria, ZnO@HMSCs showed a higher susceptibility against Grampositive bacteria. This demonstrates the promise of metal-loaded capsules as antibacterial delivery vehicles with dual-mode time release profiles being potential alternatives for antibiotic drugs.
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