Structure and Properties of Electrochemically Synthesized Silver Nanoparticles in Aqueous Solution by High-Resolution Techniques.

The aim of this work was to deeply investigate the structure and properties of electrochemically synthesized silver nanoparticles (AgNPs) through high-resolution techniques such as transmission electron microscopy (TEM), scanning electron microscopy (SEM), Zeta Potential measurements, and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Strong brightness, tendency to generate nanoclusters containing an odd number of atoms, and absence of the free silver ions in solution were observed. The research also highlighted that the chemical and physical properties of the AgNPs seemed to be related to their peculiar oxidative state as suggested by X-ray photoelectron spectroscopy (XPS) and X-ray powder diffraction (XRPD) analyses. Finally, the MTT assay tested the low cytotoxicity of the investigated AgNPs.

Hyaluronic Acid-Modified Porous Silicon Films for the Electrochemical Sensing of Bacterial Hyaluronidase.

The development of enzyme-responsive hyaluronic acid methacrylate (HYAMA)-coated porous silicon (pSi) films and their application in electrochemical diagnostic devices for the in situ detection of the enzyme hyaluronidase (hyal), which is secreted by Staphylococcus aureus (S. aureus) bacteria, are reported. The approach relies on a HYAMA-pSi electrode made of thermally hydrocarbonized pSi (pSi-THC) that is impregnated with crosslinked HYAMA/polyethylene glycol diacrylate (PEGDA) hydrogels. The enzymatic degradation of HYAMA by bacterial hyal is monitored by differential pulse voltammetry (DPV) utilizing pSi-THC as a working electrode and ferro/ferricyanide (FF) as external redox probe. The degradation of HYAMA results in reduced diffusion of the redox probe through the partially charged film, thereby enabling the detection of hyal by DPV. In addition to the determination of the concentration-dependent response in NaOAc buffer (pH 5.2), the detection of hyal as indicator for the presence of S. aureus bacteria above a threshold level in bacterial supernatants and artificial wound fluid is highlighted.

Fabrication and Characterization of a Porous Silicon Drug Delivery System with an Initiated Chemical Vapor Deposition Temperature-Responsive Coating.

This paper reports on the fabrication of a pSi-based drug delivery system, functionalized with an initiated chemical vapor deposition (iCVD) polymer film, for the sustainable and temperature-dependent delivery of drugs. The devices were prepared by loading biodegradable porous silicon (pSi) with a fluorescent anticancer drug camptothecin (CPT) and coating the surface with temperature-responsive poly(N-isopropylacrylamide-co-diethylene glycol divinyl ether) (pNIPAM-co-DEGDVE) or non-stimulus-responsive poly(aminostyrene) (pAS) via iCVD. CPT released from the uncoated oxidized pSi control with a burst release fashion (∼21 nmol/(cm(2) h)), and this was almost identical at temperatures both above (37 °C) and below (25 °C) the lower critical solution temperature (LCST) of the switchable polymer used, pNIPAM-co-DEGDVE (28.5 °C). In comparison, the burst release rate from the pSi-pNIPAM-co-DEGDVE sample was substantially slower at 6.12 and 9.19 nmol/(cm(2) h) at 25 and 37 °C, respectively. The final amount of CPT released over 16 h was 10% higher at 37 °C compared to 25 °C for pSi coated with pNIPAM-co-DEGDVE (46.29% vs 35.67%), indicating that this material can be used to deliver drugs on-demand at elevated temperatures. pSi coated with pAS also displayed sustainable drug delivery profiles, but these were independent of the release temperature. These data show that sustainable and temperature-responsive delivery systems can be produced by functionalization of pSi with iCVD polymer films. Benefits of the iCVD approach include the application of the iCVD coating after drug loading without causing degradation of the drug commonly caused by exposure to factors such as solvents or high temperatures. Importantly, the iCVD process is applicable to a wide array of surfaces as the process is independent of the surface chemistry and pore size of the nanoporous matrix being coated.

Patterning and biofunctionalization of antifouling hyperbranched polyglycerol coatings.

We demonstrate the patterned biofunctionalization of antifouling hyperbranched polyglycerol (HPG) coatings on silicon and glass substrates. The ultralow fouling HPG coatings afforded straightforward chemical handles for rapid bioconjugation of amine containing biomolecular species. This was achieved by sodium periodate oxidation of terminal HPG diols to yield reactive aldehyde groups. Patterned microprinting of sodium periodate and cell adhesion mediating cyclic peptides containing the RGD sequence resulted in an array of covalently immobilized bioactive signals. When incubated with mouse fibroblasts, the HPG background resisted cell attachment whereas high density cell attachment was observed on the peptide spots, resulting in high-contrast cell microarrays. We also demonstrated single-step, in situ functionalization of the HPG coatings by printing periodate and peptide concurrently. Our results demonstrate the effectiveness of antifouling and functionalized HPG graft polymer coatings and establish their use in microarray applications for the first time.

Surface engineering for long-term culturing of mesenchymal stem cell microarrays.

The cell microarray format can recreate a multitude of cell microenvironments on a single chip using only minimal amounts of reagent. In this study, we describe surface modifications to passivate cell microarrays, aiming to adapt the platform to the study of stem cell behavior over long-term culture periods. Functionalization of glass slides with (3-glycidyloxypropyl) trimethoxysilane enabled covalent anchoring of extracellular matrix proteins on microscale spots printed by a robotic contact printer. Subsequently, the surface was passivated by bovine serum albumin (BSA) or poly(ethylene glycol)bisamine (A-PEG) with molecular weights of 3000, 6000, and 10 000 Da. Cloud-point conditions for A-PEG grafting were attained that were compatible with protein deposition. Passivation strategies were assessed by culturing mesenchymal stem cells on the microarray platform. While both BSA and A-PEG passivation initially blocked cell adhesion between the printed spots, only A-PEG grafting was able to maintain cell pattern integrity over the entire culture period of 3 weeks.

Recent Advances in Formulations for Long-Acting Delivery of Therapeutic Peptides.

Recent preclinical and clinical studies have focused on the active area of therapeutic peptides due to their high potency, selectivity, and specificity in treating a broad range of diseases. However, therapeutic peptides suffer from multiple disadvantages, such as limited oral bioavailability, short half-life, rapid clearance from the body, and susceptibility to physiological conditions (e.g., acidic pH and enzymolysis). Therefore, high peptide dosages and dose frequencies are required for effective patient treatment. Recent innovations in pharmaceutical formulations have substantially improved therapeutic peptide administration by providing the following advantages: long-acting delivery, precise dose administration, retention of biological activity, and improvement of patient compliance. This review discusses therapeutic peptides and challenges in their delivery and explores recent peptide delivery formulations, including micro/nanoparticles (based on lipids, polymers, porous silicon, silica, and stimuli-responsive materials), (stimuli-responsive) hydrogels, particle/hydrogel composites, and (natural or synthetic) scaffolds. This review further covers the applications of these formulations for prolonged delivery and sustained release of therapeutic peptides and their impact on peptide bioactivity, loading efficiency, and (in vitro/in vivo) release parameters.

Stimulus-responsiveness and drug release from porous silicon films ATRP-grafted with poly(N-isopropylacrylamide).

In this report, we employ surface-initiated atom transfer radical polymerization (SI-ATRP) to graft a thermoresponsive polymer, poly(N-isopropylacrylamide) (PNIPAM), of controlled thickness from porous silicon (pSi) films to produce a stimulus-responsive inorganic-organic composite material. The optical properties of this material are studied using interferometric reflectance spectroscopy (IRS) above and below the lower critical solution temperature (LCST) of the PNIPAM graft polymer with regard to variation of pore sizes and thickness of the pSi layer (using discrete samples and pSi gradients) and also the thickness of the PNIPAM coatings. Our investigations of the composite's thermal switching properties show that pore size, pSi layer thickness, and PNIPAM coating thickness critically influence the material's thermoresponsiveness. This composite material has considerable potential for a range of applications including temperature sensors and feedback controlled drug release. Indeed, we demonstrate that modulation of the temperature around the LCST significantly alters the rate of release of the fluorescent anticancer drug camptothecin from the pSi-PNIPAM composite films.

Porous silicon nanomaterials: recent advances in surface engineering for controlled drug-delivery applications.

Porous silicon (pSi) nanomaterials are increasingly attractive for biomedical applications due to their promising properties such as simple and feasible fabrication procedures, tunable morphology, versatile surface modification routes, biocompatibility and biodegradability. This review focuses on recent advances in surface modification of pSi for controlled drug delivery applications. A range of functionalization strategies and fabrication methods for pSi-polymer hybrids are summarized. Surface engineering solutions such as stimuli-responsive polymer grafting, stealth coatings and active targeting modifications are highlighted as examples to demonstrate what can be achieved. Finally, the current status of engineered pSi nanomaterials for in vivo applications is reviewed and future prospects and challenges in drug-delivery applications are discussed.

Stimulus-Responsive Antibiotic Releasing Systems for the Treatment of Wound Infections.

There remains an unmet need for innovative treatments for chronic wound infections as they continue to be a financial and social burden on society. Because of the dynamic nature of wounds, this study investigated the utilization of stimulus-responsive plasma polymers for the development of pH- and thermoresponsive antibiotic delivery systems for the treatment of wound infections. Porous silicon films were loaded with the antibiotic levofloxacin (LVX) and subsequently coated with plasma polymer layers: first, poly(1,7-octadiene) (pOCT) for stability, followed by either the temperature-responsive polymer poly N,N-diethylacrylamide (pDEA) or the pH- responsive polymer poly 2-(diethylamino)ethyl methacrylate (pDEAEMA), to fabricate two delivery systems. The delivery systems were thoroughly characterized chemically and physically and tested in vitro through drug release and bacterial zone of inhibition studies. After a 16 h time point, the system containing pDEA achieved 3.2-fold greater release at 45 °C compared to 22 °C, whereas the system containing pDEAEMA achieved a 2.2-fold greater release when exposed to pH 8.5 media compared to pH 6.2 media. Furthermore, both systems retained their antimicrobial activity and demonstrated stimulus-responsive release to form zones of inhibition on relevant wound pathogens, Pseudomonas aeruginosa, Staphylococcus epidermidis and Staphylococcus aureus. Therefore, this proof-of-principle study confirms that stimulus-responsive porous silicon films can be utilized to deliver antibiotic when exposed to physiologically relevant stimuli such as pH and temperature with the potential to be applied to other pharmaceutics.

On-demand Antimicrobial Treatment with Antibiotic-Loaded Porous Silicon Capped with a pH-Responsive Dual Plasma Polymer Barrier.

Chronic wounds are a major socio-economic problem. Bacterial infections in such wounds are a major contributor to lack of wound healing. An early indicator of wound infection is an increase in pH of the wound fluid. Herein, we describe the development of a pH-responsive drug delivery device that can potentially be used for wound decontamination in situ and on-demand in response to an increase in the pH of the wound environment. The device is based on a porous silicon film that provides a reservoir for encapsulation of an antibiotic within the pores. Loaded porous silicon is capped with dual plasma polymer layers of poly(1,7-octadiene) and poly(acrylic acid), which provide a pH-responsive barrier for on-demand release of the antibiotic. We demonstrate that release of the antibiotic is inhibited in aqueous buffer at pH 5, whereas the drug is released in a sustainable manner at pH 8. Importantly, the released drug was bacteriostatic against the Pseudomonas aeruginosa wound pathogen. In the future, incorporation of the delivery device into wound dressings could potentially be utilized for non-invasive decontamination of wounds.

Microwave Heating of Poly(N-isopropylacrylamide)-Conjugated Gold Nanoparticles for Temperature-Controlled Display of Concanavalin A.

We demonstrate microwave-induced heating of gold nanoparticles and nanorods. An appreciably higher and concentration-dependent microwave-induced heating rate was observed with aqueous dispersions of the nanomaterials as opposed to pure water and other controls. Grafted with the thermoresponsive polymer poly(N-isopropylacrylamide), these gold nanomaterials react to microwave-induced heating with a conformational change in the polymer shell, leading to particle aggregation. We subsequently covalently immobilize concanavalin A (Con A) on the thermoresponsive gold nanoparticles. Con A is a bioreceptor commonly used in bacterial sensors because of its affinity for carbohydrates on bacterial cell surfaces. The microwave-induced thermal transitions of the polymer reversibly switch on and off the display of Con A on the particle surface and hence the interactions of the nanomaterials with carbohydrate-functionalized surfaces. This effect was determined using linear sweep voltammetry on a methyl-α-d-mannopyranoside-functionalized electrode.

Photonic porous silicon as a pH sensor.

Chronic wounds do not heal within 3 months, and during the lengthy healing process, the wound is invariably exposed to bacteria, which can colonize the wound bed and form biofilms. This alters the wound metabolism and brings about a change of pH. In this work, porous silicon photonic films were coated with the pH-responsive polymer poly(2-diethylaminoethyl acrylate). We demonstrated that the pH-responsive polymer deposited on the surface of the photonic film acts as a barrier to prevent water from penetrating inside the porous matrix at neutral pH. Moreover, the device demonstrated optical pH sensing capability visible by the unaided eye.

Surface-initiated hyperbranched polyglycerol as an ultralow-fouling coating on glass, silicon, and porous silicon substrates.

Anionic ring-opening polymerization of glycidol was initiated from activated glass, silicon, and porous silicon substrates to yield thin, ultralow-fouling hyperbranched polyglycerol (HPG) graft polymer coatings. Substrates were activated by deprotonation of surface-bound silanol functionalities. HPG polymerization was initiated upon the addition of freshly distilled glycidol to yield films in the nanometer thickness range. X-ray photoelectron spectroscopy, contact angle measurements, and ellipsometry were used to characterize the resulting coatings. The antifouling properties of HPG-coated surfaces were evaluated in terms of protein adsorption and the attachment of mammalian cells. The adsorption of bovine serum albumin and collagen type I was found to be reduced by as much as 97 and 91%, respectively, in comparison to untreated surfaces. Human glioblastoma and mouse fibroblast attachment was reduced by 99 and 98%, respectively. HPG-grafted substrates outperformed polyethylene glycol (PEG) grafted substrates of comparable thickness under the same incubation conditions. Our results demonstrate the effectiveness of antifouling HPG graft polymer coatings on a selected range of substrate materials and open the door for their use in biomedical applications.

Polymerization-Amplified Optical DNA Detection on Porous Silicon Templates.

A porous silicon-based optical DNA sensor is described herein, which enables rapid DNA detection. The DNA sensor relies on the specificity of the DNA base pairing in conjunction with an interferometric optical signal amplification step based on polymer formation within the porous silicon layer to detect the DNA targets in a highly selective fashion. We demonstrate that it is possible to discriminate between DNA strands exhibiting even a single nucleotide mismatch using this sensor.