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Porous silicon (PSi) nanoparticles' tunable properties are facilitating their use at highly challenging medical tasks such as peptide delivery. Because of many different mechanisms that are affecting the interaction between the peptide and the particle, the drug incorporation into the mesoporous delivery system is not straightforward. We have studied the adsorption and loading of incretin hormone glucagon like peptide 1 (GLP-1) on PSi nanoparticles. The results show that the highest loading degree can be achieved in pH values near the isoelectric point of peptide, and the phenomenon is independent of the surface's zeta potential. In order to study the interaction between the peptide and the nanoparticle, we studied the adsorption with lower concentrations and noticed that also non-Coulombic forces have a big role in adsorption of GLP-1. Adsorption is effective and pH-independent especially on low peptide concentrations and onto more hydrophobic nanoparticles. Reversibility of adsorption was studied as a function of buffer pH. When the loading is compared to the total mass of the formulation, the loading degree is 29%, and during desorption experiments 25% is released in 4 h and can be considered as a reversible loading degree. Thus, the peptides adsorbed first seem to create irreversibly adsorbed layer that facilitates reversible adsorption of following peptides.

International audience; Porous silicon (PSi) nanomaterials combine a high drug loading capacity and tunable surface chemistry with various surface modifications to meet the requirements for biomedical applications. In this work, alkyne-terminated thermally hydrocarbonized porous silicon (THCPSi) nanoparticles were fabricated and postmodified using five bioactive molecules (targeting peptides and antifouling polymers) via a single-step click chemistry to modulate the bioactivity of the THCPSi nanoparticles, such as enhancing the cellular uptake and reducing the plasma protein association. The size of the nanoparticles after modification was increased from 176 to 180-220 nm. Dextran 40 kDa modified THCPSi nanoparticles showed the highest stability in aqueous buffer. Both peptide- and polymer-functionalized THCPSi nanoparticles showed an extensive cellular uptake which was dependent on the functionalized moieties presented on the surface of the nanoparticles. The plasma protein adsorption study showed that the surface modification with different peptides or polymers induced different protein association profiles. Dextran 40 kDa functionalized THCPSi nanoparticles presented the least protein association. Overall, these results demonstrate that the "click" conjugation of the biomolecules onto the alkyne-terminated THCPSi nanoparticles is a versatile and simple approach to modulate the surface chemistry, which has high potential for biomedical applications.

The aim of the research was to verify that electrospraying of piroxicam yielded a new polymorphic form of this drug. In the experiments, piroxicam was dissolved in chloroform and the solution was atomised electrostatically. Subsequently, the charged droplets were neutralised and dried. The solid drug particles were collected and analysed by scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, high performance liquid chromatography, and infrared and Raman spectroscopy. The X-ray diffractogram measured for the electrosprayed piroxicam particles did not match with any of the known piroxicam crystal structures (Cambridge Crystallographic Data Centre). The variable temperature X-ray diffraction showed that the structure recrystallised completely into piroxicam polymorphic form I during heating. No degradation products or solvate removal was detected by high performance liquid chromatography and thermal analysis. The infrared and Raman spectra of the electrosprayed piroxicam were compared to those of form I, and some notable differences in the peak positions, shapes and intensities were detected. The results indicate that electrospraying leads to piroxicam crystallisation in a currently unknown polymorphic form.

A coaxial induction probe for measuring the charge, size and distance of a passing object is presented. Two different current signals were induced as an object passed the probes. The signals were integrated and Gaussian curves were fitted to the data. According to simulations done with Comsol Multiphysics, the charge, size and distance could be calculated from the amplitudes and widths of the curves. The system was simulated, built and calibrated. It was tested in powder measurements in a fluidized bed device.

A new one-step technique to measure the effect of ambient humidity on powder resistivity has been previously presented. In this article, we provide more experimental data obtained with five different powders. One-step measurements and traditional multi-step measurements were performed. Also, additional measurements were performed using standard resistivity cell. Results were compared and it could be concluded that the new technique provided meaningful results although significant hysteresis was observed during humidification and drying cycles. Finally, charging of the powder was also measured and it was noticed that it decreases with decreasing resistivity and increasing humidity.

The oral bioavailability of a poorly water-soluble drug is often inadequate for the desired therapeutic effect. The bioavailability can be improved by enhancing the physicochemical properties of the drug (e.g., dissolution rate, permeation across the gastrointestinal tract). Other approach include shielding the drug from the gastric metabolism and targeted drug release to obtain optimal drug absorption. In this study, a poorly water-soluble model drug, griseofulvin, was encapsulated as disordered solid dispersions into Eudragit L 100-55 enteric polymer micromatrix particles, which were produced by electrospraying. Similar micromatrix particles were also produced with griseofulvin-loaded thermally oxidized mesoporous silicon (TOPSi) nanoparticles dispersed to the polymer micromatrices. The in vitro drug dissolution at pH 1.2 and 6.8, and permeation at pH 7.4 across Caco-2/HT29 cell monolayers from the micromatrix particles, were investigated. The micromatrix particles were found to be gastro-resistant, while at pH 6.8 the griseofulvin was released very rapidly in a fast-dissolving form. Compared to free griseofulvin, the permeability of encapsulated griseofulvin across the intestinal cell monolayers was greatly improved, particularly for the TOPSi-doped micromatrix particles. The griseofulvin solid dispersions were stable during storage for 6 months at accelerated conditions. Overall, the method developed here could prove to be a useful oral drug delivery solution for improving the bioavailability of poorly water-soluble or otherwise problematic drugs.

A hybrid nanocomposite comprised by porous silicon nanoparticles and a stimuli responsive polymeric material, polyethylene glycol-block-poly(L-histidine), is spontaneously formed by nanoprecipitation in a flow-focusing microfluidic chip. The nanocomposite presents a novel hybrid compound micelle structure with a great robustness for therapeutic applications. Therefore, the nanocomposite is developed and tested as a “smart” multistage drug delivery system (MDDS) in response to some of the current problems that cancer treatment presents. Based on the stimuli-responsive behavior of the nanocomposite, a chemotherapeutic agent is successfully loaded into the nanosystem and released upon changes in the pH-values. The nanocomposite demonstrates enhanced stability in plasma, narrow size distribution, improved surface smoothness, and high cytocompatibility. Furthermore, the nanocomposite presents reduced nanoparticle internalization by phagocytic macrophage cells and pH-dependent cell growth inhibition capacity. Overall, the developed hybrid nanocomposite shows very promising features for its further development as a “smart” pH-responsive MDDS.

Two limestones and two solid wastes were tested as adsorbents for chloride and sulphate ion removal from synthetic and real alkaline process mining water. The composition and surface structure of the adsorbents were analysed by ED-XRF, XRD, SEM and MIR spectroscopy and the nitrogen adsorption method. The optimal adsorption time and amount of adsorbent were determined by batch analysis with an anion concentration of 20 mg/L. In synthetic solution adsorbents removed 99% of SO42− and 96% of Cl− and in real process water the removal rate was 85% and 74% for SO42− and Cl−, respectively. It was found that equilibrium could successfully be fitted to the Langmuir, Toth and BiLangmuir adsorption isotherms.

The main goal of the current work was to investigate the possible use of flexographic printing for the conversion of nanosuspensions into solid dosage forms. Aqueous nanosuspensions of indomethacin (IND) and itraconazole (ITR) with Poloxamer 407 as the stabilizer agent were prepared by wet ball-milling. The nanosuspensions were flexographically printed on three different substrates, including two commercially available edible substrates. The printed formulations were characterized with X-ray diffractometry (XRD) and scanning electron microscopy (SEM). In addition, dissolution studies for the printed IND and ITR formulations were conducted. The mean particle size of milled nanosuspensions of IND and ITR was 422.6 ± 7.7 nm and 698.1 ± 14.0 nm, respectively. The SEM imaging showed even distribution of nanosuspensions on the substrates after printing without any evident agglomeration. The printed formulations contained drug at least partially in crystalline form. The drug dissolution rate from the prepared formulations was improved compared to the pure drug. The drug release from the preparations on edible substrates was slightly slower due to the incorporation of the drug particles into the substrate matrix. In conclusion, the results indicated that flexographic printing can be considered as a promising fabrication method of solid nanoparticulate systems with enhanced dissolution behavior.

Combination therapy via nanoparticulate systems has already been proposed as a synergistic approach for cancer treatment. Herein, undecylenic acid modified thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs) loaded with sorafenib and surface-biofunctionalized with anti-CD326 antibody (Ab) were developed for cancer chemo-immunotherapy in MCF-7 and MDA-MB-231 breast cancer cells. The cytocompatibility study showed no significant toxicity for the bare and antibody-conjugated UnTHCPSi (Un-Ab) NPs at concentrations lower than 200 μg·mL−1. Compared to the bare UnTHCPSi, Un-Ab NPs loaded with sorafenib reduced the premature drug release in plasma, increasing the probability of proper drug targeting. In addition, high cellular interaction and subsequent internalization of the Un-Ab NPs into the cells expressing CD326 antigen demonstrated the possibility of improving antigen-mediated endocytosis via CD326 targeting. While an in vitro antitumor study revealed a higher inhibitory effect of the sorafenib-loaded Un-Ab NPs compared to the drug-loaded UnTHCPSi NPs in the CD326 positive MCF-7 cells, there was no difference in the anti-proliferation impact of both the abovementioned NPs in the CD326 negative MDA-MB-231 cells, suggesting CD326 as an appropriate receptor for Ab-mediated drug delivery. It was also shown that the anti-CD326 Ab can act as an immunotherapeutic agent by inducing antibody dependent cellular cytotoxicity and enhancing the interaction of effector immune and cancer cells for subsequent phagocytosis and cytokine secretion. Hence, the developed nanovectors can be applied for simultaneous tumor-selective drug targeting and immunotherapy.

Recent progress in research on thermally carbonized porous silicon (TCPSi) and its applications is reported. Despite a slow start, thermal carbonization has now started to gain interest mainly due to new emerging areas for applications. These new areas, such as optical sensing, drug delivery, and energy storage, require stable surface chemistry and physical properties. TCPSi is known to have all of these desired properties. Herein, the above-listed properties of TCPSi are summarized, and the carbonization processes, functionalization, and characterization of TCPSi are reviewed. Moreover, some of the emerging fields of TCPSi applications are discussed and recent advances in the fields are introduced.

In article number 1605375, Vimalkumar Balasubramanian, Helder A. Santos, and co-workers develop a new biomimetic nanoreactor based on cancer-cell-membrane material in combination with porous silicon nanoparticles. This biomimetic nanoreactors can readily be integrated with cells, reduce the intracellular reactive oxygen species levels under oxidative stress, and function as artificial organelles inside biological cells with potential applications for biomedical applications.

In article 1603239, Flavia Fontana, Helder A. Santos, and co-workers develop an innovative cancer nanovaccine by merging the adjuvant properties of the nanoparticles produced by nanoprecipitation in a microfluidic glass capillary device with high reproducibility, together with a biomimetic source of antigens derived from cancer-cell membranes. The nanovectors induce maturation of antigen-presenting cells and secretion of pro-inflammatory cytokines in vitro.

Ethionamide (ETH) is an important second-line antituberculosis drug used for the treatment of patients infected with multidrug-resistant Mycobacterium tuberculosis. Recently, we reported that the loading of ETH into thermally carbonized-porous silicon (TCPSi) nanoparticles enhanced the solubility and permeability of ETH at different pH-values and also increased its metabolization process. Based on these results, we synthesized carboxylic acid functionalized thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs) conjugated with ETH and its antimicrobial effect was evaluated against Mycobacterium tuberculosis strain H37Rv. The activity of the conjugate was increased when compared to free-ETH, which suggests that the nature of the synergy between the NPs and ETH is likely due to the weakening of the bacterial cell wall that improves conjugate-penetration. These ETH-conjugated NPs have great potential in reducing dosing frequency of ETH in the treatment of multidrug-resistant tuberculosis (MDR-TB). (C) 2016 Elsevier Ltd. All rights reserved., Fundação para a Ciência e Tecnologia (FCT, Portugal) and FEDER (European Union) for funding through UID/MULTI/04378/2013, project grant IF/00092/2014 and IF2014 position. Thanks are also due to “Comissão de Coordenação e Desenvolvimento Regional do Norte (CCDR-N)/NORTE2020/Portugal 2020” for funding through project DESignBIOtechHealth (ref. Norte-01-0145-FEDER-000024). H.A.S. acknowledges financial support from the Academy of Finland (decision nos. 252215 and 281300), the University of Helsinki Research Funds, the Biocentrum Helsinki, and the European Research Council under the European Union’s Seventh Framework Programme (FP/2007–2013, Grant No. 310892). The content is solely the responsibility of the authors and does not necessarily represent the official views of the FCT or CCDR-N, info:eu-repo/semantics/publishedVersion

In this study, electrostatic charging of lactose and its mixtures with salbutamol sulphate (SS) were studied as a function of relative humidity (RH). Powder adhesion onto a steel pipe surface was also investigated. The powders were charged by sliding in a steel pipe. Increase in RH decreased the charging of lactose and mixtures, but the effect on SS was not evident. Furthermore, the charge of the mixtures reversed from negative to positive as RH was increased and remained positive as the samples were again dried. Humidification also changed the adhesion behavior of the mixtures onto the pipe surface.

Ischemic heart disease is the leading cause of death globally. Severe myocardial ischemia results in a massive loss of myocytes and acute myocardial infarction, the endocardium being the most vulnerable region. At present, current therapeutic lines only ameliorate modestly the quality of life of these patients. Here, an engineered nanocarrier is reported for targeted drug delivery into the endocardial layer of the left ventricle for cardiac repair. Biodegradable porous silicon (PSi) nanoparticles are functionalized with atrial natriuretic peptide (ANP), which is known to be expressed predominantly in the endocardium of the failing heart. The ANP-PSi nanoparticles exhibit improved colloidal stability and enhanced cellular interactions with cardiomyocytes and non-myocytes with minimal toxicity. After confirmation of good retention of the radioisotope 111-Indium in relevant physiological buffers over 4 h, in vivo single-photon emission computed tomography (SPECT/CT) imaging and autoradiography demonstrate increased accumulation of ANP-PSi nanoparticles in the ischemic heart, particularly in the endocardial layer of the left ventricle. Moreover, ANP-PSi nanoparticles loaded with a novel cardioprotective small molecule attenuate hypertrophic signaling in the endocardium, demonstrating cardioprotective potential. These results provide unique insights into the development of nanotherapies targeted to the injured region of the myocardium.

One of the most challenging obstacles in nanoparticle's surface modification is to achieve the concept that one ligand can accomplish multiple purposes. Upon such consideration, 3-aminopropoxy-linked quercetin (AmQu), a derivative of a natural flavonoid inspired by the structure of dopamine, is designed and subsequently used to modify the surface of thermally hydrocarbonized porous silicon (PSi) nanoparticles. This nanosystem inherits several advanced properties in a single carrier, including promoted anticancer efficiency, multiple drug resistance (MDR) reversing, stimuli-responsive drug release, drug release monitoring, and enhanced particle-cell interactions. The anticancer drug doxorubicin (DOX) is efficiently loaded into this nanosystem and released in a pH-dependent manner. AmQu also effectively quenches the fluorescence of the loaded DOX, thereby allowing the use of the nanosystem for monitoring the intracellular drug release. Furthermore, a synergistic effect with the presence of AmQu is observed in both normal MCF-7 and DOX-resistant MCF-7 breast cancer cells. Due to the similar structure as dopamine, AmQu may facilitate both the interaction and internalization of PSi into the cells. Overall, this PSi-based platform exhibits remarkable superiority in both multifunctionality and anticancer efficiency, making this nanovector a promising system for anti-MDR cancer treatment.

Bioresponsive cytosolic nanobased multidelivery has been emerging as an enormously challenging novel concept due to the intrinsic protective barriers of the cells and hardly controllable performances of nanomaterials. Here, we present a new paradigm to advance nano-in-nano integration technology amenable to create multifunctional nanovehicles showing considerable promise to overcome restrictions of intracellular delivery, solve impediments of endosomal localization and aid effectual tracking of nanoparticles. A redox responsive intercalator chemistry comprised of cystine and 9-aminoacridine is designed as a cross-linker to cap carboxylated porous silicon nanoparticles with DNA. These intelligent nanocarriers are then encapsulated within novel one-pot electrostatically complexed nano-networks made of a zwitterionic amino acid (cysteine), an anionic bioadhesive polymer (poly(methyl vinyl ether-alt-maleic acid)) and a cationic endosomolytic polymer (polyethyleneimine). This combined nanocomposite is successfully tested for the co-delivery of hydrophobic (sorafenib) or hydrophilic (calcein) molecules loaded within the porous core, and an imaging agent covalently integrated into the polyplex shell by click chemistry. High loading capacity, low cyto- and hemo-toxicity, glutathione responsive on-command drug release, and superior cytosolic delivery are shown as achievable key features of the proposed formulation. Overall, formulating drug molecules, DNA and imaging agents, without any interference, in a physico-chemically optimized carrier may open a path towards broad applicability of these cost-effective multivalent nanocomposites for treating different diseases.

The encapsulation of drugs to nanoparticles may offer a solution for targeted delivery. Here, we set out to engineer a self-assembling targeting ligand by combining the functional properties of human transferrin and fungal hydrophobins in a single fusion protein. We showed that human transferrin can be expressed in Nicotiana benthamiana plants as a fusion with Trichoderma reesei hydrophobins HFBI, HFBII, or HFBIV. Transferrin-HFBIV was further expressed in tobacco BY-2 suspension cells. Both partners of the fusion protein retained their functionality; the hydrophobin moiety enabled migration to a surfactant phase in an aqueous two-phase system, and the transferrin moiety was able to reversibly bind iron. Coating porous silicon nanoparticles with the fusion protein resulted in uptake of the nanoparticles in human cancer cells. This study provides a proof-of-concept for the functionalization of hydrophobin coatings with transferrin as a targeting ligand.

We report an advanced drug delivery platform for combination chemotherapy by concurrently incorporating two different drugs into microcompoistes with ratiometric control over the loading degree. Atorvastatin and celecoxib were selected as model drugs due to their different physicochemical properties and synergetic effect on colorectal cancer prevention and inhibition. To be effective in colorectal cancer prevention and inhibition, the produced microcomposite contained hypromellose acetate succinate, which is insoluble in acidic conditions but highly dissolving at neutral or alkaline pH conditions. Taking advantage of the large pore volume of porous silicon (PSi), atorvastatin was firstly loaded into the PSi matrix, and then encapsulated into the pH-responsive polymer microparticles containing celecoxib by microfluidics in order to obtain multi-drug loaded polymer/PSi microcomposites. The prepared microcomposites showed monodisperse size distribution, multistage pH-response, precise ratiometric controlled loading degree towards the simultaneously loaded drug molecules, and tailored release kinetics of the loaded cargos. This attractive microcomposite platform protects the payloads from being released at low pH-values, and enhances their release at higher pH-values, which can be further used for colon cancer prevention and treatment. Overall, the pH-responsive polymer/PSi-based microcomposite can be used as a universal platform for the delivery of different drug molecules for combination therapy.

Thermally hydrocarbonized porous silicon (THCPSi) microparticles were loaded with indomethacin (IMC) and griseofulvin (GSV) using three different payloads between 6.2-19.5 and 6.2-11.4 wt %, respectively. The drug loading parameters were selected to avoid crystallization of the drug molecules on the external surface of the particles that would block the pore entrances. The successfulness of the loadings was verified with TG, DSC, and XRPD measurements. The effects of the confinement of IMC and GSV into the small mesopores of THCPSi were analyzed with helium pycnometry, FTIR, and NMR spectroscopy. The results showed the density of the THCPSi loaded drugs to be ca. 10% lower than the bulk crystalline forms, while a melt quenched amorphous drugs showed a density reduction of 3-7.5%. DSC and FTIR results confirmed that the drugs reside in an amorphous form within the THCPSi pores. Similar results were obtained with NMR, which also indicated that IMC may reside as both amorphous clusters and individual molecules within the pores. The (1)H transverse relaxation times (T2) of amorphous and THCPSi loaded drugs showed IMC relaxation times of 0.28 ms for both the cases, whereas for GSV the values were 0.32 and 0.39 ms, respectively, indicating similar limited mobility in both cases. The results indicated that strong drug-carrier interactions were not necessary for stabilizing the amorphous state of the adsorbed drug. Dissolution tests using biorelevant media, fasted state simulated intestinal fluid (FaSSIF) and simulated gastric fluid (SGF), showed that THCPSi-loaded IMC and GSV were rapidly released in FaSSIF with comparable rates to the amorphous forms, whereas in SGF the THCPSi reduced the pH dependency in the dissolution of IMC.

The development of a stable vehicle with low toxicity, high cellular internalization, efficient endosomal escape, and optimal drug release profile is a key bottleneck in nanomedicine. To overcome all these problems, we have developed a successful layer-by-layer method to covalently conjugate polyethyleneimine (PEI) and poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) copolymer on the surface of undecylenic acid functionalized thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs), forming a bilayer zwitterionic nanocomposite containing free positive charge groups of hyper-branched PEI disguised by the PMVE-MA polymer. The surface smoothness, charge and hydrophilicity of the developed NPs considerably improved the colloidal and plasma stabilities via enhanced suspensibility and charge repulsion. Furthermore, despite the surface negative charge of the bilayer polymer-conjugated NPs, the cellular trafficking and endosomal escape were significantly increased in both MDA-MB-231 and MCF-7 breast cancer cells. Remarkably, we also showed that the conjugation of surface free amine groups of the highly toxic UnTHCPSi-PEI (Un-P) NPs to the carboxylic groups of PMVE-MA renders acceptable safety features to the system and preserves the endosomal escape properties via proton sponge mechanism of the free available amine groups located inside the hyper-branched PEI layer. Moreover, the double layer protection not only controlled the aggregation of the NPs and reduced the toxicity, but also sustained the drug release of an anticancer drug, methotrexate, with further improved cytotoxicity profile of the drug-loaded particles. These results provide a proof-of-concept evidence that such zwitterionic polymer-based PSi nanocomposites can be extensively used as a promising candidate for cytosolic drug delivery.

Glucagon like peptide-1 (GLP-1) is an incretin hormone that is in the pipeline for type 2 diabetes mellitus (T2DM) therapy. However, oral administration of GLP-1 is hindered by the harsh conditions of the gastrointestinal tract and poor bioavailability. In this study, three nanosystems composed by three different biomaterials (poly(lactide-co-glycolide) polymer (PLGA), Witepsol E85 lipid (solid lipid nanoparticles, SLN) and porous silicon (PSi) were developed and loaded with GLP-1 to study their permeability in vitro. All the nanoparticles presented a size of approximately 200 nm. The nanoparticles' interaction with the mucus and the intestinal cells were enhanced after coating with chitosan (CS). PSi nanosystems presented the best association efficiency (AE) and loading degree (LD), even though a high AE was also observed for PLGA nanoparticles and SLN. Among all the nanosystems, PLGA and PSi were the only nanoparticles able to sustain the release of GLP-1 in biological fluids when coated with CS. This characteristic was also maintained when the nanosystems were in contact with the intestinal Caco-2 and HT29-MTX cell monolayers. The CS-coated PSi nanoparticles showed the highest GLP-1 permeation across the intestinal in vitro models. In conclusion, PLGA + CS and PSi + CS are promising nanocarriers for the oral delivery of GLP-1.

Porous silicon (PSi) based particulate systems are emerging as an important drug delivery system due to its advantageous properties such as biocompatibility, biodegradability and ability to tailor the particles' physicochemical properties. Here, annealed thermally hydrocarbonized PSi (AnnTHCPSi) and undecylenic acid modified AnnTHCPSi (AnnUnTHCPSi) microparticles were developed as a PSi-based platform for oral delivery of insulin. Chitosan (CS) was used to modify the AnnUnTHCPSi microparticles to enhance the intestinal permeation of insulin. Surface modification with CS led to significant increase in the interaction of PSi microparticles with Caco-2/HT-29 cell co-culture monolayers. Compared to pure insulin, the CS-conjugated microparticles significantly improved the permeation of insulin across the Caco-2/HT-29 cell monolayers, with ca. 20-fold increase in the amount of insulin permeated and ca. 7-fold increase in the apparent permeability (P(app)) value. Moreover, among all the investigated particles, the CS-conjugated microparticles also showed the highest amount of insulin associated with the mucus layer and the intestinal Caco-2 cells and mucus secreting HT-29 cells. Our results demonstrate that CS-conjugated AnnUnTHCPSi microparticles can efficiently enhance the insulin absorption across intestinal cells, and thus, they are promising microsystems for the oral delivery of proteins and peptides across the intestinal cell membrane.

The use of nanoparticle carriers for the sustained release of cytotoxic drugs in cancer therapy can result in fewer adverse effects and can thus be of great benefit for the patient. Recently, a novel nanocomposite, prepared by the encapsulation of THCPSi nanoparticles within solid lipids (SLN), was developed and characterized as a promising drug delivery carrier in vitro. The present study describes the in vivo evaluation of unmodified THCPSi nanoparticles and THCPSi-solid lipid nanocomposites (THCPSi-SLNCs) as potential drug delivery carriers for cancer therapy by using (18)F radiolabeling for the detection of the particle biodistribution in mice. Passive tumor targeting of (18)F-THCPSis and (18)F-THCPSi-SLNCs by the enhanced permeation and retention effect was investigated in a murine breast cancer model. Encapsulation of THCPSi nanoparticles with solid lipids improved their accumulation in tumors at a 7 week time point (tumor-to-liver ratio 0.10 ± 0.08 and 0.24 ± 0.09% for (18)F-THCPSis and (18)F-THCPSi-SLNCs, respectively).

When nanocarriers are used for drug delivery they can often achieve superior therapeutic outcomes over standard drug formulations. However, concerns about their adverse effects are growing due to the association between exposure to certain nanosized particles and cardiovascular events. Here we examine the impact of intravenously injected drug-free nanocarriers on the cardiovasculature at both the systemic and organ levels. We combine in vivo and in vitro methods to enable monitoring of hemodynamic parameters in conscious rats, assessments of the function of the vessels after sub-chronic systemic exposure to nanocarriers and evaluation of the direct effect of nanocarriers on vascular tone. We demonstrate that nanocarriers can decrease blood pressure and increase heart rate in vivo via various mechanisms. Depending on the type, nanocarriers induce the dilation of the resistance arteries and/or change the responses induced by vasoconstrictor or vasodilator drugs. No direct correlation between physicochemical properties and cardiovascular effects of nanoparticles was observed. The proposed combination of methods empowers the studies of cardiovascular adverse effects of the nanocarriers.

A multifunctional nano-in-micro drug delivery platform is developed by conjugating the porous silicon nanoparticles with mucoadhesive polymers and subsequent encapsulation into a pH-responsive polymer using microfluidics. The multistage platform shows monodisperse size distribution and pH-responsive payload release, and the released nanoparticles are mucoadhesive. Moreover, this platform is capable of simultaneously loading and releasing multidrugs with distinct properties.

The effect of adsorption and confinement on ibuprofen was studied by immersion loading the molecules into porous silicon (PSi) microparticles. The PSi microparticles were modified into thermally oxidized PSi (TOPSi) and thermally hydrocarbonized PSi (THCPSi) to evaluate the effects of the loading solvent and the surface chemistry on the obtainable drug payloads. The payloads, location, and the molecular state of the adsorbed drug were evaluated using thermal analysis. The results showed that after the adsorption of ∼800 mg/cm3 (wdrug/vpores) of drug into the mesopores, depending on the solvent used in the immersion, the drug began to rapidly recrystallize on the external surface of the particles. Moderate concentrations, however, enabled payloads of 800–850 mg/cm3 without excessive surface crystallization, and thus, there was no need for rinsing the samples to remove the externally crystallized portion. The results showed that the confined ibuprofen forms nanocrystals inside of the mesopores after approxi...

Diatoms are porous silica-based materials obtained from single cell photosynthetic algae. Despite low cost, easy purification process, environmentally safe properties, and rapidly increasing potentials for medical applications, the cytotoxicity of diatoms and the effect on drug permeation of oral formulations have not been studied so far. Herein, we have evaluated the potential of diatom silica microparticles (DSMs) for the delivery of mesalamine and prednisone, which are two commonly prescribed drugs for gastrointestinal (GI) diseases. Transmission electron microscopy analysis of the morphological surface changes of Caco-2/HT-29 monolayers and the cell viability data in colon cancer cells (Caco-2, HT-29 and HCT-116) showed very low toxicity of diatoms at concentrations up to 1000 mg/mL. The mesalamine and prednisone release under simulated GI conditions indicated prolonged release of both drugs from the diatoms. Furthermore, drug permeation across Caco-2/HT-29 co-culture monolayers demonstrated that diatoms are capable to enhance the drug permeability. Overall, this study evaluated DSMs’ cytotoxicity in colon cancer cells and the effect of DSMs on drug permeability across Caco-2/HT-29 monolayers. Our results demonstrate that DSMs can be considered as a non-cytotoxic biomaterial with high potential to improve the mesalamine and prednisone bioavailability by sustaining the drug release and enhancing drug permeability., Financial support from the Academy of Finland (decision numbers 252215 and 256394), the University of Helsinki, the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013) grant no. 310892 and the ERDF through the Atlantic Area Transnational Cooperation Programme Project 2011-1/164 MARMED are gratefully acknowledged. T.H. Silva acknowledges the Portuguese Foundation for Science and Technology for a post-doc grant (SFRH/BPD/34704/2007). We thank Prof. Lauri A. Aaltonen (Genome-Scale Biology Program & Department of Medical Genetics, University of Helsinki, Finland) for generously providing the HCT-116 cells and Prof. Bruno Sarmento (INEB - Instituto de Engenharia Biomedica, Porto) for kindly providing the HT-29 cells. Pei Ting Mah (University of Otago, New Zeeland) is acknowledged for technical support with the XRPD instrument.

Nanotechnology employs multifunctional engineered materials in the nanoscale range that provides many opportunities for translational stem cell research and therapy. Here, a cell-penetrating peptide (virus-1 transactivator of transcription)-conjugated, porous silicon nanoparticle (TPSi NP) loaded with the Wnt3a protein to increase both the cell survival rate and the delivery precision of stem cell transplantation via a combinational theranostic strategy is presented. The TPSi NP with a pore size of 10.7 nm and inorganic framework enables high-efficiency loading of Wnt3a, prolongs Wnt3a release, and increases antioxidative stress activity in the labeled mesenchymal stem cells (MSCs), which are highly beneficial properties for cell protection in stem cell therapy for myocardial infarction. It is confirmed that the intracellular aggregation of TPSi NPs can highly amplify the acoustic scattering of the labeled MSCs, resulting in a 2.3-fold increase in the ultrasound (US) signal compared with that of unlabeled MSCs. The translational potential of the designed nanoagent for real-time US imaging-guided stem cell transplantation is confirmed via intramyocardial injection of labeled MSCs in a nude mouse model. It is proposed that the intracellular aggregation of protein drug-loaded TPSi NPs could be a simple but robust strategy for improving the therapeutic effect of stem cell therapy.

Electrospraying was used in drug particle production.The aim of the research was to evaluate the possibilities to produce drug particles with desired pharmaceutical properties by electrospraying. In particular, the effect of drying pressure on particle properties was studied.A poorly water soluble model drug (budesonide) was dissolved in chloroform, and the solution was atomized by electrospraying. Following this, the charged droplets were neutralized and dried in a drying chamber. The pressure in the drying chamber was varied. The dried particles were collected and analyzed.The pressure reduction had a slight impact on particle size distribution. The particles produced in reduced pressure turned out to be notably more porous than the particles produced in atmospheric pressure. The pressure reduction also affects the degree of crystallinity of the product. The dissolution of the particles produced in reduced pressures was faster to a certain extent than that of the particles produced in atmospheric pressure.A setup for electrospraying materials in a reduced pressure was presented. The pressure reduction had a notable impact on particle morphology. The possibilities to tailor the particle properties during electrospraying were studied.

Despite steadily increasing insights on the biocompatibility of PSi nanoparticles (NPs), an extensive biosafety study on the immune and red blood cells (RBCs) is still lacking. Herein, we evaluated the impact of the PSi NPs' surface chemistry on immune cells and human RBCs both in vitro and in vivo. Negatively charged hydrophilic and hydrophobic PSi NPs caused less ATP depletion and genotoxicity than the positively charged amine modified hydrophilic PSi NPs, demonstrating the main role of PSi NPs' surface charge on the immunocompatibility profile. Furthermore, cells with lower metabolic activity, longer doubling time, and shorter half-life were more sensitive to the concentration- and time-dependent toxicity in the following order: T-cells ≈ monocytes > macrophages ≈ B-cells. RBC hemolysis and imaging assay revealed a significant correlation between the surface chemistry, the amount of the PSi NPs adsorbed on the cell surface and the extent of morphological changes. The in vivo results showed that despite mild renal steatosis, glomerular degeneration, hepatic central vein dilation and white pulp shrinkage in spleen, no notable changes were observed in the serum level of biochemical and hematological factors. This study is a comprehensive demonstration of the mechanistic direct and indirect genotoxicity effects of PSi NPs, elucidating the most influencing properties for the PSi NPs' design.

Some general points regarding the fabrication of thermally carbonized and hydrocarbonized porous silicon-based optical filters are discussed. The differences between the two carbonization treatments are pointed out, and methods for further functionalization are presented. Finally, the effects of the aforementioned surface functionalization methods are evaluated, and usefulness of the resulting chemically modified optical structures in biosensing applications is demonstrated.

Fe-modified mordenite, ferrierite, Y, ZSM-5, ZSM-12 and beta zeolite catalysts were prepared by solid state ion-exchange and conventional liquid phase ion-exchange methods from aqueous solutions. Sn- modified H-beta-300 zeolite catalyst was prepared by the later method. The characterization of proton form, Fe and Sn modified zeolites was carried out using X-ray powder diffraction, scanning electron microscopy, Mossbauer spectroscopy with magnetic measurements, transmission electron microscopy, nitrogen adsorption, X-ray absorption spectroscopy, X-ray photoelectron spectroscopy, inductively coupled plasma spectroscopy, thermo-gravimetric analysis and FTIR spectroscopy using pyridine as a probe molecule. Isomerization of α-pinene oxide over the Fe and Sn modified zeolite catalysts was carried out in the liquid phase using a batch-wise glass reactor. Formation of campholenic aldehyde and fencholenic aldehyde were observed to be influenced by the structure, acidity of zeolite and contents of Fe and Sn, reaction temperature and the catalysts pretreatment.

Evaporation rates play a key role in evaporation crystallization and the drying of crystal products. Raman analysis was used to study the effect of the evaporation rate on the polymorphs of indomethacin at room temperature. The studied solvents were highly volatile ethanol, acetone, and ethyl acetate. The approach was based on a mass transfer model of evaporation, and experimental flux measurements were used for model evaluation. Evaporation rates from porous carriers were also investigated. The studied mesoporous silicon microparticles can be used in oral dosage forms of poorly soluble active pharmaceutical ingredients. Evaporation rates of dimethyl sulfoxide from a pure solvent, from indomethacin solutions, and from solutions containing microparticles were measured at 100 °C. An evaporation rate model of porous particles was used and the predicted results were compared with the experimental results obtained.

Influenza A viruses (IAVs) cause recurrent epidemics in humans, with serious threat of lethal worldwide pandemics. The occurrence of antiviral-resistant virus strains and the emergence of highly pathogenic influenza viruses have triggered an urgent need to develop new anti-IAV treatments. One compound found to inhibit IAV, and other virus infections, is saliphenylhalamide (SaliPhe). SaliPhe targets host vacuolar-ATPase and inhibits acidification of endosomes, a process needed for productive virus infection. The major obstacle for the further development of SaliPhe as antiviral drug has been its poor solubility. Here, we investigated the possibility to increase SaliPhe solubility by loading the compound in thermally hydrocarbonized porous silicon (THCPSi) nanoparticles. SaliPhe-loaded nanoparticles were further investigated for the ability to inhibit influenza A infection in human retinal pigment epithelium and Madin-Darby canine kidney cells, and we show that upon release from THCPSi, SaliPhe inhibited IAV infection in vitro and reduced the amount of progeny virus in IAV-infected cells. Overall, the PSi-based nanosystem exhibited increased dissolution of the investigated anti-IAV drug SaliPhe and displayed excellent in vitro stability, low cytotoxicity, and remarkable reduction of viral load in the absence of organic solvents. This proof-of-principle study indicates that PSi nanoparticles could be used for efficient delivery of antivirals to infected cells.

Aim of the study was to investigate how hydrothermal carbonization changes adsorption efficiency toward metal ions of typical sludges. Hydrothermal carbonization is a novel and green method of treating biomasses. Reactions take place in an aqueous environment at relatively mild temperature and high pressure resulting a different end biomass structure than obtained from traditional pyrolysis. Anaerobically digested sludge (ADS) and pulp and paper industry sludge (INS) were utilized as a feedstock. Adsorption behavior of ADS and INS was examined towards Pb(II), Cr(III), Cr(VI), As(III) and As(V). Both ADS and INS were found to remove Pb(II) effectively and followed Sips adsorption isotherm. Adsorption kinetics was fast and followed pseudo-second order model. Furthermore, intraparticle diffusion was observed to be partly responsible in the adsorption process. Hydrothermal carbonization indicated high potential for the production of novel carbonaceous materials for metal removal from waters.

Journal of molecular catalysis / A 366, 228-237 (2013). doi:10.1016/j.molcata.2012.09.028, Published by Elsevier Science, Amsterdam [u.a.]

We present a method for measuring powder resistivity as a function of moisture using a one-step process. The developed new resistivity cell consists of narrow horizontal electrode surrounded by a grounded guard electrode and simultaneous measurement of humidity within the powder bed. The system was modeled using computer simulations. As an example, resistivities of three different lactoses, wheat flour and quartz are presented. Resistivity was found to decrease several orders of magnitude between 10 RH% and 90 RH%. Simulated results showed that if no guard plate is used, measurement errors caused by humidity gradient are of order of magnitude.

A major bottleneck in nanometer-scale drug delivery systems is the fabrication of nanocarriers with excellent stability under physiological conditions that can both efficiently encapsulate therapeutic agents and controllably release their payloads. Herein, the formation of a novel nanocomposite based on the encapsulation of thermally hydrocarbonized porous silicon (THCPSi) nanoparticles with solid lipid nanoparticles (SLNs) on a 1:1 ratio is described. The THCPSi-SL nanocomposites (THCPSi-SLNCs) are formed using a solid-in-oil-in-water emulsion solvent evaporation method. TEM and FTIR analyses prove that THCPSi nanoparticles are successfully encapsulated in the SLN matrix. The formation of the THCPSi-SLNCs alters the surface smoothness and hydrophobicity of the THCPSi nanoparticles, and also remarkably enhances their stability in human plasma. After encapsulation, the cytocompatibility of the THCPSi nanoparticles with intestinal, liver, and macrophage cancer cells is also greatly improved. A prolonged release of the model drug, furosemide, from THCPSi-SLNC is achieved, indicating that the SLN matrix successfully seals the pores of the THCPSi nanoparticles. Flow cytometry and confocal fluorescence microscopy studies demonstrates the significantly reduced cellular association of THCPSi-SLNCs with the cells comparing to bare THCPSi nanoparticles. Overall, the THCPSi-SLNCs exhibits superior suspensibility and better stability against aggregation in aqueous buffer solutions, increases the particle surface smoothness and cytocompatibility, reduces the cellular association, increases the in vitro stability in human plasma, and prolonges the drug release. These results suggest that the nanocomposite is a promising nanovector system for drug delivery applications.

A new biomimetic nanoreactor design is presented based on cancer cell membrane material in combination with porous silicon nanoparticles. This cellular nanoreactor features a biocompartment enclosed by a cell membrane and readily integrated with cells and supplementing the cellular functions under oxidative stress. The study demonstrates the impact of the nanoreactors on improving cellular functions with a potential to serve as artificial organelles.

Zinc oxide (ZnO) nanorods were manufactured using the aqueous chemical growth (ACG) method, and the effect of thermal acetylene treatment on their morphology, chemical composition, and optical properties was investigated. Changes in the elemental content of the treated rods were found to be different than in previous reports, possibly due to the different defect concentrations in the samples, highlighting the importance of synthesis method selection for the process. Acetylene treatment resulted in a significant improvement of the ultraviolet photoluminescence of the rods. The greatest increase in emission intensity was recorded on ZnO rods treated at the temperature of 825 °C. The findings imply that the changes brought on by the treatment are limited to the surface of the ZnO rods. Electronic supplementary material The online version of this article (doi:10.1186/s11671-016-1627-y) contains supplementary material, which is available to authorized users.

Aim: To investigate porous silicon (PSi) nanoparticles (NPs) behavior in the embryonic brain. Materials & methods: Fluorescently labeled PSi NPs were injected into the embryonic brains intraventricularly and to the mother intravenously (iv.). Brain histology from different time points up to 3 days was analyzed and live brains imaged with two-photon microscopy. Results: PSi NPs were able to penetrate 80% of the embryonic cortical depth. Particle motility was confirmed in real-time in vivo. PSi NPs were able to penetrate the embryonic cortex after either iv. maternal or intraventricular injection. No developmental of macromorphological changes or increased cell apoptosis was observed. Conclusion: PSi NPs penetrate deep in the brain tissues of embryos after intraventricular injection and after iv. injection to the mother.

Immunoadjuvant porous silicon (PSi)-based nanovaccines are prepared by nanoprecipitation in a glass capillary microfluidics device. Vesicles, derived from cancer cell membranes encapsulating thermally oxidized PSi nanoparticles or PSi-polymer nanosystems binding a model antigen, are biocompatible over a wide range of concentrations, and show immunostimulant properties in human cells, promoting the expression of co-stimulatory signals and the secretion of pro-inflammatory cytokines.

Gold nanorods, DNA origami, and porous silicon nanoparticle-functionalized biocompatible double emulsion are developed for versatile molecular targeted therapeutics and antibody combination therapy. This advanced photothermal responsive all-in-one biocompatible platform can be easily formed with great therapeutics loading capacity for different cancer treatments with synergism and multidrug resistance inhibition, which has great potential in advancing biomedical applications.

Flightless I (Flii), a cytoskeletal actin remodelling protein, is elevated in wounds and is a negative regulator of wound healing. Gene silencing using small interfering RNA (siRNA) is an attractive approach to antagonize Flii, and therefore holds significant promise as a therapeutic intervention. The development of siRNA therapeutics has been limited by an inability of the siRNA to cross the cell surface plasma membrane of target cells and also by their degradation due to endogenous nuclease action. To overcome these limitations, suitable delivery vehicles are required. Porous silicon (pSi) is a biodegradable and high surface area material commonly used for drug delivery applications. Here we investigated the use of pSi nanoparticles (pSiNPs) for the controlled release of Flii siRNA to wounds. Thermally hydrocarbonized pSiNPs (THCpSiNPs) were loaded with Flii siRNA and then coated with a biocompatible chitosan layer. Loading regimens in the order of 50 μg of Flii siRNA per mg of pSi were achieved. The release rate of Flii siRNA was sustained over 35 h. With addition to keratinocytes in vitro, reduced Flii gene expression in conjunction with lowered Flii protein was observed, in concert with increased cell migration and proliferation. A significant improvement in the healing of acute excisional wounds compared to controls was observed from day 5 onward when Flii siRNA-THCpSiNPs were intradermally injected. THCpSiNPs therefore are an effective vehicle for delivering siRNA, and nanoparticle-based siRNA delivery represents a promising therapeutic approach to improve wound healing. Refereed/Peer-reviewed

Purpose To study how water plasticization affects the molecular mobility and crystallization tendency of freeze-dried trehalose, sucrose, melibiose and cellobiose. Methods Freeze-dried disaccharides were subjected to different relative humidity atmospheres and their physical stabilities were evaluated. Lyophilizate water sorption tendencies and glass transition temperatures were modeled using Brunauer-Emmett-Teller (BET) and Gordon-Taylor (GT) equations, respectively. Sucrose and cellobiose crystallization tendencies were compared by using the concept of reduced crystallization temperature (RCT), and the molecular mobilities of trehalose and melibiose were compared by measuring their T1H relaxation time constants. Results Based on the BET and GT models, water sorption tendency and the resulting plasticizing effect were different in sucrose when compared to the other disaccharides. Trehalose and melibiose exhibited generally slower crystallization rates when compared to sucrose and cellobiose. Amorphous melibiose was shown to be particularly stable within the studied water content range, whichmay have partly been caused by its relatively slow molecular mobility. Conclusions Slow amorphous-to-crystalline transition rate is known to be important for lyoprotecting excipients when formulating a robust drug product. The physical stabilities of amorphous trehalose and melibiose even with relatively high water contents might make their use advantageous in this respect compared to sucrose and cellobiose.

Thermally carbonized porous silicon (TCPSi) microparticles were chemically modified with organofunctional alkoxysilane molecules using a silanization process. Before the silane coupling, the TCPSi surface was activated by immersion in hydrofluoric acid (HF). Instead of regeneration of the silicon hydride species, the HF immersion of silicon carbide structure forms a silanol termination (Si-OH) on the surface required for silanization. Subsequent functionalization with 3-aminopropyltriethoxysilane provides the surface with an amine (-NH(2)) termination, while the SiC-type layer significantly stabilizes the functionalized structure both mechanically and chemically. The presence of terminal amine groups was verified with FTIR, XPS, CHN analysis, and electrophoretic mobility measurements. The overall effects of the silanization to the morphological properties of the initial TCPSi were analyzed and they were found to be very limited, making the treatment effects highly predictable. The maximum obtained number of amine groups on the surface was calculated to be 1.6 groups/nm(2), corresponding to 79% surface coverage. The availability of the amine groups for further biofunctionalization was confirmed by successful biotinylation. The isoelectric point (IEP) of amine-terminated TCPSi was measured to be at pH 7.7, as opposed to pH 2.6 for untreated TCPSi. The effects of the surface amine termination on the cell viability of Caco-2 and HT-29 cells and on the in vitro fenofibrate release profiles were also assessed. The results indicated that the surface modification did not alter the loading of the drug inside the pores and also retained the beneficial enhanced dissolution characteristics similar to TCPSi. Cellular viability studies also showed that the surface modification had only a limited effect on the biocompatibility of the PSi.

Advances in nanotechnology have prompted rapid progress and versatile imaging modalities for diagnostics and treatment of diseases. Molecular imaging is a powerful technique for quantifying physiological changes in vivo using noninvasive imaging probes. These probes are used to image specific cells and tissues within a whole organism. Currently, imaging is an essential part of clinical protocols providing morphological, structural, metabolic and functional information. Using theranostic micro- or nanoparticles, which combine both therapeutic and diagnostic capabilities in one single entity, holds a true promise to propel the biomedical field toward personalized medicine. With this approach, biological processes can be directly and simultaneously monitored with the treatment of the diseases. This mini-review highlights the recent innovative diagnostic imaging aspects of porous silicon (PSi) materials and emphasizes their potential as theranostic platforms and tools for the clinic. Multiple biomedical imaging applications of the PSi materials are also outlined.

Oat seeds have an oil content of up to 13 %, of which up to 34 % can be polar lipids (glycolipids and phospholipids). Because of their amphiphilic structure, these polar lipids are potential emulsifiers. In this study, polar lipid fraction from oat produced by a supercritical fluid extraction process was fractionated into different polar lipid classes by HPLC and the lipid classes in subfractions were identified by comparing retention times with reference compounds and performing co-injections. The oat polar lipid fraction contained monogalactosyldiacylglycerol, digalactosyldiacylglycerol, steryl glycoside, and phosphatidyl choline, and also possibly phosphatidyl inositol. The polar lipid fraction was also used as an emulsifier to produce oil-in-water emulsions with different amounts of emulsifier and oil, and the stability and other properties of emulsions were studied. Emulsions were formed quite easily, but they were prone to rapid creaming even after a couple of days of storage at ambient conditions. Droplet size and droplet size distribution of the emulsions seemed to be slightly smaller with smaller amount of oil and larger amount of emulsifier. Generally, the droplet size of the emulsions was in the range of 0.2–4 μm, and with the largest amount of oil (5 %, w/v) up to 10 μm. The upper phase of creamed emulsions contained slightly larger droplets, up to 30 μm, while the lower phase retained smaller droplets. Microscopic investigation revealed that the increase in droplet size of the upper phase was mainly due to aggregation, which implies that these emulsions may be stable against coalescence to some extent.