Functionalized Calcium Carbonate Research Articles

Comparison of the liquisolid technique and co-milling for loading of a poorly soluble drug in inorganic porous excipients

Drug loading into mesoporous carriers may help to improve the dissolution of poorly aqueous-soluble drugs. However, both preparation method and carrier properties influence loading efficiency and drug release. Accordingly, this study aimed to compare two preparation methods: formulation into liquisolid systems (LSS) and co-milling for their efficiency in loading the poorly soluble model drug cyclosporine A (CyA) into mesoporous magnesium aluminometasilicate Neusilin® US2 (NEU) or functionalized calcium carbonate (FCC). Scanning electron microscopy was used to visualize the morphology of the samples and evaluate the changes that occurred during the drug loading process. The solid-state characteristics and physical stability of the formulations, prepared at different drug concentrations, were determined using X-ray powder diffraction. In vitro release of the drug was evaluated in biorelevant media simulating intestinal fluid. The obtained results revealed improved drug release profiles of the formulations when compared to the milled (amorphous) CyA alone. The dissolution of CyA from LSS was faster in comparison to the co-milled formulations. Higher drug release was achieved from NEU than FCC formulations presumably due to the higher pore volume and larger surface area of NEU.

Functionalized calcium carbonate (FCC) as a novel carrier to solidify supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS)

Functionalized calcium carbonate (FCC), a novel pharmaceutical excipient, has shown promising properties in the field of oral drug delivery. The current study aimed at evaluating the feasibility of FCC as a carrier for the solidification of self-nanoemulsifying drug delivery systems (SNEDDS) containing the poorly water-soluble model drug carvedilol (CRV). Conventional, subsaturated SNEDDS (80 %-SNEDDSliquid) and supersaturated SNEDDS (200 %-SNEDDSliquid) were loaded onto FCC via physical adsorption at three ratios; 2.5:1, 3.0:1 and 3.5:1 (w/w) of FCC:SNEDDSliquid, respectively, generating free-flowing powders (SNEDDSFCC) with drug loading ranging from 0.8 % to 2.6 % (w/w) CRV. The emulsification of SNEDDSFCC in a USP II dissolution setup (in purified water) was characterized using dynamic light scattering, resulting in similar droplet sizes and PDIs as observed for their liquid counterparts. The morphology and physical state of the obtained SNEDDSFCC were characterized using scanning electron microscopy and differential scanning calorimetry. The physical stability and drug release upon dispersion were assessed as a function of storage time. The 200 %-SNEDDSliquid were physically stable for 6 days, however, solidification using FCC stabilized the supersaturated concentrations of CRV for a test period of up to 10 weeks (solidification ratios 3.0:1 and 3.5:1 (FCC:SNEDDSliquid)). SNEDDSFCC achieved an improved rate and extent of drug release upon dispersion compared to the crystalline CRV in tap water (pH 7.5), however, to a lesser extent than their liquid counterparts. After 8 weeks of storage (25 °C at dry conditions), FCC was still able to rapidly release the SNEDDSliquid and demonstrated the same rate and extent of drug release as freshly prepared samples. The solidification of 200 %-SNEDDSliquid in presence of FCC greatly improved the drug loading and showed an enhanced drug release profile compared to the conventional systems. In conclusion, FCC showed potential as a carrier for solidification of SNEDDS and for the development of novel supersaturated solid SNEDDS for the oral delivery of poorly water-soluble drugs.

Remediation of Pb(II) and Cd(II) in polluted waters with calcium thioglycolate–modified straw biochar

The pollution of water bodies by heavy metals (HMs) such as Pb(II) and Cd(II) poses a serious environmental risk. Herein, rice straw biochar (RBC) modified with calcium thioglycolate was used to remove Pb(II) and Cd(II) from aqueous solutions. The adsorption performance of the modified biochar was investigated via adsorption kinetics and isotherm model fitting. Furthermore, scanning electron microscopy (SEM), X-ray energy-dispersive spectroscopy (EDS), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS) were used to elucidate the modification and adsorption mechanisms. The results showed that the modification process loaded sulfur-containing functional groups, calcium carbonate, and calcium oxalate crystals on the biochar surface, considerably enhancing its complexation performance and ion-exchange capacity. The equilibrium adsorption amounts for Pb(II) and Cd(II) reached 124.92 and 65.44 mg g−1 in unary systems, respectively; they reached 121.34 and 39.43 mg g−1 in a binary Pb(II) and Cd(II), respectively. Moreover, the optimal adsorption conditions were as follows: pH = 6, temperature = 25 °C, dosage = 0.8 g L−1, and contact time = 2 h. In the binary Pb(II) and Cd(II) system, the adsorption process obeyed the Langmuir competitive adsorption model, which means that one adsorption site on the modified biochar was effective for only one heavy-metal ion, and the modified biochar was more selective for Pb(II) than for Cd(II). The adsorption mechanism, which was dominated by chemisorption, mainly involved complexation, precipitation, ion exchange, and cation-π interactions. Meanwhile, adsorption and desorption experiments indicated that the modified biochar exhibited satisfactory recycling performance, demonstrating its feasibility as an inexpensive and efficient heavy-metal adsorbent for polluted water.

Amino acid promoted single-step carbon dioxide capture and mineralization integrated with polymer-mediated crystallization of carbonates

Integrated CO2 capture and mineralization is a promising technology for cutting CO2 emissions and associated environmental impacts. Two major challenges in CO2 mineralization in aqueous media are (1) the lack of green and energy-efficient processes and (2) limited applications of the produced carbonates. Here, we present a very efficient, environmentally friendly, and convenient integrated CO2 capture and mineralization method to produce functional calcium carbonate (CaCO3) particles. We use a gas diffuser reaction setup to bubble CO2 in liquid media containing reagents such as amino acid as CO2 absorption promotor, water-soluble polymers as crystal growth modifiers, and Ca2+ ions. Different concentrations of amino acid L-arginine with a fixed CO2 bubbling rate were investigated for Ca2+ conversion. At the optimized conditions, more than 90% Ca2+ was converted to CaCO3 within 5 min of CO2 bubbling at a nominal rate. Additionally, functional carbonates that could be used as dye, heavy metals adsorbents, and functional composite fillers are produced using crystal growth modifiers. The method is simple, efficient, eco-friendly, and could be used for CO2/Ca2+-rich industrial waste valorization.

Physicochemical and biological characterization of functionalized calcium carbonate

Biocompatible and osteoconductive calcium carbonate (CC) and hydroxyapatite (HAP) have been studied as bone filling materials. In contrast to HAP, CC is highly resorbable, and to achieve optimal resorption rates, a functionalized calcium carbonate (FCC) consisting of CC particles with a HAP layer has been further developed. The aim of this study was to characterize the physicochemical and biological properties of FCC.Physicochemical properties were studied with ATR-FTIR, XRD and SEM. pH change and ion release were studied in a static system in cell culture medium or water, and in a continuous dynamic system in Tris-buffer. Viability and morphology of pre-osteoblastic cells in vitro was studied with a WST method, as well as with SEM and TEM imaging.There was a minor increase in pH in Tris-buffer and water dissolution systems at the beginning of FCC dissolution. In contrast, pH of the cell culture medium remained approximately unchanged during the dissolution. In Tris-buffer and water dissolution systems, increased levels of calcium release from FCC were detected, whereas in the cell culture medium FCC was shown to adsorb calcium from the medium, thus causing a decrease in the dissolved calcium concentration. This was associated with decreased viability of cells. Interestingly SEM and TEM imaging revealed internalization of FCC particles by the cells.This study showed that FCC, similar to natural bone mineral, carbonated apatite has a capability to adsorb calcium from surrounding liquid. This needs to be carefully considered when cell culture assays are performed with these types of materials.

Ag/Ag3PO4 Nanoparticle-Decorated Hydroxyapatite Functionalized Calcium Carbonate: Ultrasound-Assisted Sustainable Synthesis, Characterization, and Antimicrobial Activity

Silver nanoparticles are usually prepared by the reduction of silver cations through chemical and non-sustainable procedures that involve the use of reducing chemical agents. Therefore, many efforts have been made in the search for sustainable alternative methods. Among them, an ultrasound-assisted procedure could be a suitable and sustainable method to afford well-dispersed and nanometric silver particles. This paper describes a sustainable, ultrasound-assisted method using citrate as a reducing agent to prepare silver@hydroxyapatite functionalized calcium carbonate composites. For comparison, an ultrasound-assisted reduction was performed in the presence of NaBH4. The composites obtained in the presence of these two different reducing agents were compared in terms of nanoparticle nature, antimicrobial activity, and cytotoxic activity. The nanoparticle nature was investigated by several techniques, including X-ray powder diffraction, field-emission scanning electron microscopy, transmission electron microscopy, UV-Vis spectroscopic measurements, and X-ray photoemission spectroscopy. Nanoparticles with a predominance of Ag or Ag3PO4 were obtained according to the type of reducing agent used. All composites were tested for antimicrobial and antibiofilm activities against Gram-positive and Gram-negative (Staphylococcus aureus and Pseudomonas aeruginosa, respectively) bacteria and for cytotoxicity towards human skin keratinocytes and human fibroblasts. The nature of the nanoparticles, Ag or Ag3PO4, and their predominance seemed to affect the in vitro silver release and the antimicrobial and antibiofilm activities. The composites obtained by the citrate-assisted reduction gave rise to the best results.

A New Challenge for the Old Excipient Calcium Carbonate: To Improve the Dissolution Rate of Poorly Soluble Drugs.

Calcium carbonate is an excipient traditionally used in solid dosage forms with several functions such as a diluent, a quick dissolution agent, a buffer and an opacifier. Recently, many other challenges have arisen for calcium carbonate and, among them, the possibility of using it as an excipient for improving the dissolution rate of poorly soluble drugs. As a consequence of their poor solubility in biological fluids, many active ingredients suffer from low and erratic bioavailability when administered by the oral route and thus, many formulation strategies and excipients have been proposed to overcome this problem. Among them, calcium carbonate has been proposed as an excipient for improving dissolution rates. Calcium carbonate has many interesting characteristics, in fact it dissolves quickly in gastric fluid, is inexpensive and is safe. It exists in different polymorphic forms and in porous morphology and recently a porous functionalized calcium carbonate has been proposed as a new excipient. This review is the first overview on the use of calcium carbonate as an excipient for improving drug dissolution rates. The drug loading procedure, the physical characterization of the drug/CaCO3 samples and their dissolution profiles will be described. Moreover, the possible mechanisms of dissolution improvement, such as the presence of the drug in amorphous or polymorphic forms, in small crystals, and the effects of CaCO3 dissolution in acidic medium will be discussed. Different polymorphic forms of calcium carbonate and the presence of porosity and functionalization will be analyzed as well and their effects on dissolution rates will be discussed.

Stony coral tissue loss disease decimated Caribbean coral populations and reshaped reef functionality

Diseases are major drivers of the deterioration of coral reefs and are linked to major declines in coral abundance, reef functionality, and reef-related ecosystems services. An outbreak of a new disease is currently rampaging through the populations of the remaining reef-building corals across the Caribbean region. The outbreak was first reported in Florida in 2014 and reached the northern Mesoamerican Reef by summer 2018, where it spread across the ~450-km reef system in only a few months. Rapid spread was generalized across all sites and mortality rates ranged from 94% to <10% among the 21 afflicted coral species. Most species of the family Meandrinadae (maze corals) and subfamily Faviinae (brain corals) sustained losses >50%. This single event further modified the coral communities across the region by increasing the relative dominance of weedy corals and reducing reef functionality, both in terms of functional diversity and calcium carbonate production. This emergent disease is likely to become the most lethal disturbance ever recorded in the Caribbean, and it will likely result in the onset of a new functional regime where key reef-building and complex branching acroporids, an apparently unaffected genus that underwent severe population declines decades ago and retained low population levels, will once again become conspicuous structural features in reef systems with yet even lower levels of physical functionality.

Porous Coatings to Control Release Rates of Essential Oils to Generate an Atmosphere with Botanical Actives.

Essential oils have been used in diverse areas such as packaging, agriculture and cosmetics, for their antimicrobial and pesticide activity. The organic volatile compounds of the essential oils are involved in its activity. Controlling their release helps to prolong their functionality. In this study, a functionalized calcium carbonate porous coating was employed to control the release of thyme and rosemary oil in a confined space. The release rate was evaluated at 7 °C and 23 °C, gravimetrically. It was shown that the capillary effect of the porous coating slowed down the release of the volatiles into the headspace compared to the bulk essential oil. A linear drive force model was used to fit the obtained data from both essential oils. The model showed that rosemary reached the asymptotic mass loss equilibrium faster than thyme. This result can be explained by the diverse composition and concentration of monoterpenoids between the two essential oils. Temperature and degree of loading also played important roles in the desorption of the essential oils. It was observed that at high degrees of loading and temperatures the desorption of essential oils was higher. The above-described technology could be used for applications related to food preservation, pest control among others.

Cockle shell-derived nanoparticles for optical urea biosensor development based on reflectance transduction

An optical biosensor for urea based on urease enzyme immobilised on functionalised calcium carbonate nanoparticles (CaCO 3 -NPs) was successfully developed in this study. CaCO 3 -NPs were synthesised from discarded cockle shells via a simple and eco-friendly approach, followed by surface functionalisation with succinimide ester groups. The fabricated biosensor is comprised of two layers. The first (bottom layer) contained functionalised NPs covalently immobilised to urease, and the second (uppermost layer) was alginate hydrogel physically immobilised to the pH indicator phenolphthalein. The biosensor provided a colorimetric indication of increasing urea concentrations by changing from colourless to pink. Quantitative urea analysis was performed by measuring the reflectance intensity of the colour change at a wavelength of 633.16 nm. The determination of urea concentration using this biosensor yielded a linear response range of 30–1000 mM (R 2 = 0.9901) with a detection limit of 17.74 mM at pH 7.5. The relative standard deviation of reproducibility was 1.14%, with no signs of interference by major cations, such as K + , Na + , NH₄ + , and Mg 2+ . The fabricated biosensor showed no significant difference with the standard method for the determination of urea in urine samples.

Silver@Hydroxyapatite functionalized calcium carbonate composites: characterization, antibacterial and antibiofilm activities and cytotoxicity

Silver@Hydroxyapatite functionalized calcium carbonate composites have been prepared through different sustainable methods, without involving the use of organic solvents and additional reagents. The composites were characterized by X-ray powder diffraction, field emission scanning electron microscopy, transmission electron microscopy, spectrophotometric measurements and X-ray photoemission spectroscopy. From the characterization techniques, the obtained nanoparticles resulted constituted essentially by Ag3PO4 nanostructures, whose size varied from 70 to 100 nm and were uniformly distributed on the calcium carbonate surface. Upon VIS irradiation, the formation of plasmonic nanostructures with a more defined dimensional distribution and reduced size could be obtained, as a prove of a partial silver reduction. All composites exhibited good antimicrobial and antibiofilm activities against Staphylococcus aureus and Pseudomonas aeruginosa whereas they showed low cytotoxicity effects towards human skin keratinocytes and human fibroblasts. These results enable these composites to be promising candidates for biomedical and pharmaceutical applications.

Hydroxyapatite Functionalized Calcium Carbonate Composites with Ag Nanoparticles: An Integrated Characterization Study.

In the present work, composite materials very promising for biomedical and pharma-ceutical applications were investigated. They are composed of silver nanoparticles (Ag NPs) in a matrix constituted of calcium carbonate functionalized with hydroxyapatite (HA-FCC). The composites were obtained by different synthesis methods, starting from a mixture of the silver acetate with HA-FCC (using adsorption or mixing in wet conditions methods) and then treating them by exposure to visible light or calcination to promote the silver reduction; a synthetic procedure based on ultrasound-assisted reduction with NaBH4 or citrate was also carried out. The characterization by X-ray photoelectron spectroscopy and reflected electron energy loss spectroscopy analysis also involved the reference sample of HA-FCC matrix. Then the morphology of the Ag NPs and the crystalline structure of HA-FCC were studied by transmission electron microscopy and X-ray diffraction, respectively. To assess the effectiveness of the different methods on silver reduction, the Auger parameters α’ were calculated and compared. The use of this methodology based on the Auger parameter is neither trivial nor ordinary. We demonstrate its validity since the different values of this parameter allow to identify the oxidation state of silver and consequently to evaluate the formation yield of metallic Ag NPs in the HA-FCC matrix and the effectiveness of the different reduction methods used.

Impact of Bimodal Particle Size Distribution Ratio of Functional Calcium Carbonate Filler on Thermal and Flowability Properties of Polyamide 12

In previous investigations, it was shown that the melting, as well as crystallization behavior of polyamide 12, could be manipulated by adjusting the particle size distribution of calcium carbonate as a functional filler. It was demonstrated that the melt properties of this compound show a significant dependency on the filler volume-based particle size. As finer and narrower the calcium carbonate particles in the polymer matrix become, the less influence the filler has on the melting properties, influencing the melt flow less significantly than the same surface amount of broad size distribution coarse calcium carbonate filler particles. However, due to increased nucleation, the crystallization behavior on cooling showed a markedly more rapid onset in the case of fine sub-micrometer filler particle size. To control further and optimize the thermal response properties of a filling compound for improved properties in additive manufacturing processing through selective laser sintering, the possibility to combine precisely defined particle size distributions has been studied, thereby combining the benefits of each particle size range within the chosen material size distribution contributes to the matrix. The melt flow at 190 °C, the melting speed, melting and crystallization point as well as crystallization time at 170 °C were analyzed. The thermal and flow properties of a polyamide 12 matrix can potentially be optimized with a combination of a precise amount of coarse and fine calcium carbonate filler. The improvements were exemplified using a twin-screw extruder for compounding, indicating the potential for optimizing functionally filled polymer in additive manufacturing.

Improved in vitro bioavailability of a newly developed functionalized calcium carbonate salt as a food ingredient and its comparison with available commercial calcium salts

The bioaccessibility and bioavailability of a functionalized Calcium (Ca) salt as food ingredient, based on modified Ca carbonate and hydroxyapatite (FCC), was determined and compared with frequently used Ca sources (Ca citrate tetrahydrate (CCT), tri-Ca phosphate (triCP) and Ca carbonate (CC). Results showed a similar Ca bioaccessibility for CCT (76.44 ± 9.73%), CC (73.7 ± 8.18%) and FCC (74.4 ± 1.87%) and a lower value for tri-CP (46.07 ± 8.68%). FCC showed the highest bioavailability, 5.68 ± 0.26%, compared to CC, CCT and tri-CP (3.93 ± 0.99%, 3.41 ± 0.33%, 1.85 ± 0.34%, respectively). The innovative chemical composition and structure of FCC based on amorphous hydroxyapatite combined with Ca carbonate, a greater porosity, lower agglomerates and particle size, improve the Ca solubility in the intestinal media, explaining the similar bioaccessibility but higher bioavailability of FCC compared to CCT, tri-CP and CC.

Spontaneous In Situ Formation of Liposomes from Inert Porous Microparticles for Oral Drug Delivery.

Despite the wide-spread use of liposomal drug delivery systems, application of these systems for oral purposes is limited due to their large-scale formulation and storage issues. Proliposomes are one of the formulation approaches for achieving solid powders that readily form liposomes upon hydration. In this work, we investigated a dry powder formulation of a model low-soluble drug with phospholipids loaded in porous functionalized calcium carbonate microparticles. We characterized the liposome formation under conditions that mimic the different gastrointestinal stages and studied the factors that influence the dissolution rate of the model drug. The liposomes that formed upon direct contact with the simulated gastric environment had a capacity to directly encapsulate 25% of the drug in situ. The emerged liposomes allowed complete dissolution of the drug within 15 min. We identified a negative correlation between the phospholipid content and the rate of water uptake. This correlation corroborated the results obtained for the rate of dissolution and liposome encapsulation efficiency. This approach allows for the development of solid proliposomal dosage formulations, which can be scaled up with regular processes.

Functionalised calcium carbonate as a coformer to stabilize amorphous drugs by mechanochemical activation

The aim of this study was to investigate the amorphization, physical stability and drug release of a model drug, carvedilol (CAR), when loaded onto functionalised calcium carbonate (FCC) using mechanochemical activation (vibrational ball milling). The solid-state characteristics and physical stability of CAR–FCC samples, prepared at different weight ratios and for different milling times, were determined using differential scanning calorimetry and X-ray powder diffraction. Upon milling CAR–FCC samples containing 50% CAR, amorphization of CAR was observed after 10 min. For CAR–FCC samples milled for either 30 or 90 min, it was found that CAR was amorphised at all ratios (10–90% CAR), but FCC remained crystalline. The glass transition temperature (Tgα) of the various CAR–FCC samples milled for 90 min was found to be similar (38 °C) for all ratios containing 20% CAR and above. The similar Tgαs for the different drug ratios indicate deposition of amorphous CAR onto the surface of FCC. For CAR–FCC samples containing 10% CAR, a Tgα of 49 °C was found, which is 11 °C higher compared with other CAR–FCC samples. This may indicate restricted molecular mobility resulting from CAR molecules that are in close contact with the FCC surface. The physical stability, under both stress (100 °C) and non-stress conditions (25 °C at dry conditions), showed that drug concentrations up to 30% CAR can be stabilized in the amorphous form for at least 19 weeks under non-stress conditions when deposited onto FCC, compared to less than a week physical stability of neat amorphous CAR. In vitro drug release showed that CAR–FCC samples containing 60% CAR and below can improve the drug release and generate supersaturated systems compared to neat amorphous and crystalline CAR. Samples with lower drug concentrations (40% CAR and below) can maintain supersaturation during 360 min of dissolution testing. This study indicates that the crystalline inorganic material, FCC, can facilitate amorphization of drugs, provide stabilization against drug crystallization, and improve dissolution properties of amorphous drugs upon mechanochemical activation.

Evaluation of the potential of functionalised calcium carbonate as carrier for essential oils with regard to antimicrobial packaging applications

Functionalised calcium carbonates (FCCs) are inorganic mineral‐based particles with a high porosity and extended surface area consisting of hydroxyapatite and calcium carbonate crystal structures. Therefore, FCCs have a high potential to be used as a carrier for active substances such as essential oils (EOs), which are well known for their antimicrobial activities, and control their release in antimicrobial packaging applications. In this study, different EOs were loaded on FCCs, and their antimicrobial activities were studied against Listeria innocua in in vitro tests and in food tests using sliced cooked chicken breast. FCCs loaded with thyme or oregano EO (10 wt%) showed the highest reduction in microbial load in in vitro tests at 37°C (≥8.6 log cfu/filter) as well as at 7°C after 6 days (≥7.0 log cfu/filter for thyme EO and 6.5 log cfu/filter for oregano EO). However, in food tests, FCC loaded with either EO did not show any significant antimicrobial activity. FCCs loaded with cinnamon or rosemary EO (10 wt%) did not show any significant antimicrobial activity in in vitro tests. On the other hand, they showed a significant reduction in microbial load (1.7 log cfu/g for cinnamon and 2 log cfu/g for rosemary) in food tests. Differences in antimicrobial activities in in vitro and food tests are probably due to the interaction of the components of the EOs and the components of the food such as fat and proteins.

Simultaneous investigation of the liquid transport and swelling performance during tablet disintegration.

Fast disintegrating tablets have commonly been used for fast oral drug delivery to patients with swallowing difficulties. The different characteristics of the pore structure of such formulations influence the liquid transport through the tablet and hence affect the disintegration time and the release of the drug in the body. In this work, terahertz time-domain spectroscopy and terahertz pulsed imaging were used as promising analytical techniques to quantitatively analyse the impact of the structural properties on the liquid uptake and swelling rates upon contact with the dissolution medium. Both the impact of porosity and formulation were investigated for theophylline and paracetamol based tablets. The drug substances were either formulated with functionalised calcium carbonate (FCC) with porosities of 45% and 60% or with microcrystalline cellulose (MCC) with porosities of 10% and 25%. The terahertz results reveal that the rate of liquid uptake is clearly influenced by the porosity of the tablets with a faster liquid transport observed for tablets with higher porosity, indicating that the samples exhibit structural similarity in respect to pore connectivity and pore size distribution characteristics in respect to permeability. The swelling of the FCC based tablets is fully controlled by the amount of disintegrant, whereas the liquid uptake is driven by the FCC material and the interparticle pores created during compaction. The MCC based formulations are more complex as the MCC significantly contributes to the overall tablet swelling. An increase in swelling with increasing porosity is observed in these tablets, which indicates that such formulations are performance-limited by their ability to take up liquid. Investigating the effect of the microstructure characteristics on the liquid transport and swelling kinetics is of great importance for reaching the next level of understanding of the drug delivery, and, depending on the surface nature of the pore carrier function, in turn controlling the performance of the drug mainly in respect to dissolution in the body.

Fully inkjet-printed glucose assay fabricated on highly porous pigment coating

A simple paper-based microfluidic device, fabricated on a highly porous coating consisting of functionalised calcium carbonate (FCC) pigment and a microfibrillated cellulose (MFC) and/or polyvinyl alcohol (PVOH) binder, was developed for glucose detection. Both the hydrophobic patterns, consisting of alkyl ketene dimer (AKD), and the enzyme ink, consisting of glucose oxidase (GOx), horseradish peroxidase (HRP) and an indicator containing 4-aminoantipyrine (4-AAP), and sodium 3,5-dichloro-2-hydroxy-benzenesulphonic acid (DHBS) were inkjet-printed. Multiple coating formulations were tested using two indicators, potassium iodide (KI) and 4-AAP/DHBS, to find the optimal formulation with regard to detection sensitivity and assay stability. Higher binder concentrations increased the enzyme activity, especially in the case of PVOH. Two coatings, containing either solely MFC or both MFC and PVOH were ultimately chosen for the glucose assay experiments. For the assays, a 42 nl volume of buffered enzyme solution, containing a total of 5.04 mU GOx and approximately 1.01 mU HRP, in combination with 4 mM 4-AAP and 8 mM DHBS, was printed, and a 1 µl glucose solution, made up over a range of concentrations, was applied onto the samples to evaluate the response. A good linearity was achieved between detection and glucose concentration between 0.1 and 0.6 mM with both coatings. The assays remained stable for four weeks when stored at − 20 °C. The results show that the functional coated substrates offer a viable alternative to cellulose-based substrates for microfluidic applications enabling the use of small reagent and sample volumes.

Magnetic and silver nanoparticle functionalized calcium carbonate particles—Dual functionality of versatile, movable delivery carriers which can surface-enhance Raman signals

Multifunctional probes play an increasing role even beyond applications in biomedicine. Multifunctionality introduced by the dual types of complementary probes is always attractive because, in this case, functionalized objects inherit the function of both materials. Porous calcium carbonate microparticles are becoming popular carriers of biomolecules and biosensors, as well as imaging enhancers. We demonstrate here a dual function of these carriers by incorporating both magnetic and silver nanoparticles. Magnetic nanoparticles enable movements and displacements by a magnetic field, while silver nanoparticles provide surface-enhanced Raman signal amplification necessary for the detection of biomolecules. Application of such dual-functional carriers is foreseen beyond the applications of biomedicine and theranostics.