Search

In this study, the structural attributes of nanoparticles obtained by a renewable and non-immunogenic "inulinated" analog of the "pegylated" PLA (PEG-PLA) were examined, together with the potential of these novel nanocarriers in delivering poorly water-soluble drugs. Characterization of INU-PLA assemblies, encompassing critical aggregation concentration (CAC), NMR, DLS, LDE, and SEM analyses, was conducted to elucidate the core/shell architecture of the carriers and in vitro cyto- and hemo-compatibility were assayed. The entrapment and in vitro delivery of sorafenib tosylate (ST) were also studied. INU-PLA copolymers exhibit distinctive features: (1) Crew-cut aggregates are formed with coronas of 2–4 nm; (2) a threshold surface density of 1 INU/nm2 triggers a configuration change; (3) INU surface density influences PLA core dynamics, with hydrophilic segment stretching affecting PLA distribution towards the interface. INU-PLA2NPs demonstrated an outstanding loading of ST and excellent biological profile, with effective internalization and ST delivery to HepG2 cells, yielding a comparable IC50. [ABSTRACT FROM AUTHOR]

In this paper, the authors investigate the possibility of applying artificial intelligence algorithms to the outputs of a low-cost Kalman filter-based navigation solution in order to achieve performance similar to that of high-end MEMS inertial sensors. To further improve the results of the prototype and simultaneously lighten filter requirements, different AI models are compared in this paper to determine their performance in terms of complexity and accuracy. By overcoming some known limitations (e.g., sensitivity on the dimension of input data from inertial sensors) and starting from Kalman filter applications (whose raw noise parameter estimates were obtained from a simple analysis of sensor specifications), such a solution presents an intermediate behavior compared to the current state of the art. It allows the exploitation of the power of AI models. Different Neural Network models have been taken into account and compared in terms of measurement accuracy and a number of model parameters; in particular, Dense, 1-Dimension Convolutional, and Long Short Term Memory Neural networks. As can be excepted, the higher the NN complexity, the higher the measurement accuracy; the models' performance has been assessed by means of the root-mean-square error (RMSE) between the target and predicted values of all the navigation parameters. [ABSTRACT FROM AUTHOR]

In recent years, the overall performances of inertial Micro-Electro Mechanical Sensors (MEMSs) exhibited substantial improvements to values very close or similar to so-called tactical-grade sensors. However, due to their high costs, numerous researchers are currently focusing on the performance enhancement of cheap consumer-grade MEMS inertial sensors for all those applications (as an example, small unmanned aerial vehicles, UAVs), where cost effectiveness is a relevant request; the use of redundancy proves to be a feasible method for this purpose. In this regard, the authors propose, hereinafter, a suitable strategy aimed at fusing raw measurements provided by multiple inertial sensors mounted on a 3D-printed structure. In particular, accelerations and angular rates measured by the sensors are averaged according to weights associated with the results of an Allan variance approach; the lower the noise figure of the sensors, the greater their weight on the final averaged values. On the other hand, possible effects on the measurements due to the use of a 3D structure in reinforced ONYX (a material capable of providing better mechanical specifications for avionic applications with respect to other solutions for additive manufacturing) were evaluated. The performance of a prototype implementing the considered strategy is compared with that of a tactical-grade inertial measurement unit in stationary conditions, exhibiting differences as low as 0.3 degrees in heading measurements. Moreover, the reinforced ONYX structure does not significantly affect the measured values in terms of both thermal and magnetic field while assuring better mechanical characteristics with respect to other 3D printing materials, thanks to a tensile strength of about 250 MPa and a specific stacking sequence of continuous fibers. Finally, a test conducted on an actual UAV highlights performance very close to that of a reference unit, with root-mean-square error in heading measurements as low as 0.3 degrees in observation intervals up to 140 s. [ABSTRACT FROM AUTHOR]

In this contribution, we report a strategy to enhance the therapeutic action of the chemotherapeutic Sorafenib (SRB) through its combination with a multifunctional β-cyclodextrin-based polymer able to deliver nitric oxide (NO) and emit green fluorescence upon visible light excitation (PolyCDNO). The basically water-insoluble SRB is effectively encapsulated in the polymeric host (1 mg mL−1) up to a concentration of 18 μg mL−1. The resulting host-guest supramolecular complex is able to release SRB in sink conditions and to preserve very well the photophysical and photochemical properties of the free PolyCDNO, as demonstrated by the similar values of the NO release and fluorescence emission quantum efficiencies found. The complex PolyCDNO/SRB internalizes in HEP-G2 hepatocarcinoma, MCF-7 breast cancer and ACHN kidney adenocarcinoma cells, localizing in all cases mainly at the cytoplasmic level. Biological experiments have been performed at SRB concentrations below the IC50 and with light doses producing NO at nontoxic concentrations. The results demonstrate exceptional mortality levels for PolyCDNO/SRB upon visible light irradiation in all the different cell lines tested, indicating a clear synergistic action between the chemotherapeutic drug and the NO. These findings can open up exciting avenues to potentiate the anticancer action of SRB and, in principle, to reduce its side effects through its use at low dosages when in combination with the photo-regulated release of NO. [ABSTRACT FROM AUTHOR]

Systems for accurate attitude and position monitoring of large structures, such as bridges, tunnels, and offshore platforms are changing in recent years thanks to the exploitation of sensors based on Micro-ElectroMechanical Systems (MEMS) as an Inertial Measurement Unit (IMU). Currently adopted solutions are, in fact, mainly based on fiber optic sensors (characterized by high performance in attitude estimation to the detriment of relevant costs large volumes and heavy weights) and integrated with a Global Position System (GPS) capable of providing low-frequency or single-update information about the position. To provide a cost-effective alternative and overcome the limitations in terms of dimensions and position update frequency, a suitable solution and a corresponding prototype, exhibiting performance very close to those of the traditional solutions, are presented and described hereinafter. The solution leverages a real-time Kalman filter that, along with the proper features of the MEMS inertial sensor and Real-Time Kinematic (RTK) GPS, allows achieving performance in terms of attitude and position estimates suitable for this kind of application. The results obtained in a number of tests underline the promising reliability and effectiveness of the solution in estimating the attitude and position of large structures. In particular, several tests carried out in the laboratory highlighted high system stability; standard deviations of attitude estimates as low as 0.04° were, in fact, experienced in tests conducted in static conditions. Moreover, the prototype performance was also compared with a fiber optic sensor in tests emulating actual operating conditions; differences in the order of a few hundredths of a degree were found in the attitude measurements. [ABSTRACT FROM AUTHOR]

The paper deals with performance enhancement of low-cost, consumer-grade inertial sensors realized by means of Micro Electro-Mechanical Systems (MEMS) technology. Focusing their attention on the reduction of bias instability and random walk-driven drift of cost-effective MEMS accelerometers and gyroscopes, the authors hereinafter propose a suitable method, based on a redundant configuration and complemented with a proper measurement procedure, to improve the performance of low-cost, consumer-grade MEMS sensors. The performance of the method is assessed by means of an adequate prototype and compared with that assured by a commercial, expensive, tactical-grade MEMS inertial measurement unit, taken as reference. Obtained results highlight the promising reliability and efficacy of the method in estimating position, velocity, and attitude of vehicles; in particular, bias instability and random walk reduction greater than 25% is, in fact, experienced. Moreover, differences as low as 0.025 rad and 0.89 m are obtained when comparing position and attitude estimates provided by the prototype and those granted by the tactical-grade MEMS IMU. [ABSTRACT FROM AUTHOR]

The presence of rare but highly tumorigenic cancer stem cells (CSCs) within the tumors is recognized as one of the major reasons of failure of conventional chemotherapies, mainly attributed to the development of drug resistance and increasing metastatic potential. Here, we propose a therapeutic strategy based on the simultaneous delivery of docetaxel (DTX) and the photosensitizer meso-tetraphenyl chlorine disulfonate (TPCS2a) using hyaluronic acid (HA) coated polymeric nanoparticles (HA-NPs) for the targeting and killing of CD44 over-expressing breast cancer (BC) cells, both differentiated and CSCs (CD44high/CD24low population), thus combining chemotherapy and photodynamic therapy (PDT). Using the CD44high MDA-MB-231 and the CD44low MCF-7 cells, we demonstrated the occurrence of CD44-mediated uptake of HA-NPs both in monolayers and mammosphere cultures enriched in CSCs. Cell treatments showed that combination therapy using co-loaded NPs (HA@DTX/TPCS2a-NPs) had superior efficacy over monotherapies (HA@DTX-NPs or HA@TPCS2a-NPs) in reducing the self-renewal capacity, measured as mammosphere formation efficiency, and in eradicating the CSC population evaluated with aldehyde dehydrogenase activity assay and CD44/CD24 immunostaining. In summary, these in vitro studies demonstrated for the first time the potential of the combination of DTX-chemotherapy and TPCS2a-PDT for killing CSCs using properly designed NPs. [ABSTRACT FROM AUTHOR]

Nanoparticles (NPs) based on amphiphilic block copolymers of polyethylene glycol (PEG) and biodegradable polyesters are of particular current interest in drug nanodelivery due to their easily manipulated properties. The interaction of these NPs with biological environments is highly influenced by shell features, which drive biological identity after administration. To widen the strategies available for tuning particle surface chemistry, here we developed a panel of amine-bearing PEGylated NPs with a poly(ε-caprolactone) (PCL) core for the delivery of lipophilic drugs, and investigated the impact of NP modifications on their interaction with abundant circulating proteins (human serum albumin—HSA—and mucin), as well as their transport through biological barriers (artificial mucus—AM, extracellular matrix—ECM). We prepared NPs based on a diamino-terminated PCL (amine-NPs) and its mixture with PEG-PCL copolymers (amine/PEG-NPs) at different PEG molecular weights by nanoprecipitation, as well as corresponding NPs of PEG-PCL (PEG-NPs). The presence of an amine-bearing polymer resulted in NPs with a net positive charge and a zeta potential dependent on the length of PEG in the copolymer. Amine/PEG-NPs had a larger fixed aqueous layer thickness as compared to PEG-NPs, suggesting that PEG conformation is affected by the presence of positive charges. In general, amine-bearing NPs promptly interacted with the dysopsonic protein HSA, due to electrostatic interactions, and lose stability, thereby undergoing time-related aggregation. On the other hand, amine/PEG-NPs interaction with mucin induced switching to a negative surface charge but did not alter the quality of the dispersion. The transport kinetics of NPs through a layer of artificial mucus and tumor extracellular matrix was studied by means of fluorescent NPs based upon FRET. Amine/PEG-NPs did not cross the ECM, but they were promptly transported through the AM, with swifter transport noted at increasing MWs of PEG in the copolymer. Finally, we demonstrated that all the different NP types developed in this study are internalized by human monocytes and, despite the positive charge, they did not induce a measurable inflammatory effect. In conclusion, we showed that the concurrent presence of both PEG and amine groups on NP surface is a promising strategy for directing their interaction with body compartments. While PEG-NPs are confirmed for their capacity to cross ECM-like compartments, amine/PEG-NPs are revealed as a powerful platform to widen the arsenal of nanotools available for overcoming mucus-covered epithelia. [ABSTRACT FROM AUTHOR]