Delivery Capability Research Articles

Hyaluronic Acid: A Review of the Drug Delivery Capabilities of This Naturally Occurring Polysaccharide.

The inclusion of physiologically active molecules into a naturally occurring polymer matrix can improve the degradation, absorption, and release profile of the drug, thus boosting the therapeutic impact and potentially even reducing the frequency of administration. The human body produces significant amounts of polysaccharide hyaluronic acid, which boasts exceptional biocompatibility, biodegradability, and one-of-a-kind physicochemical features. In this review, we will examine the clinical trials currently utilizing hyaluronic acid and address the bright future of this versatile polymer, as well as summarize the numerous applications of hyaluronic acid in drug delivery and immunomodulation.

Cyclodextrin-based supramolecular nanoparticles break the redox balance in chemodynamic therapy-enhanced chemotherapy

Drug delivery based on abnormal features of the tumor microenvironment (TME) has attracted considerable interest worldwide. In this study, we proposed an applicable strategy to increase the reactive oxygen species (ROS) and inhibit glutathione (GSH), in an effort to amplify oxidative damage in prostate cancer cells. Specifically, we developed dual-responsive supramolecular self-assembled nanoparticles (NPs) based on polymerized methacrylic acid (MA) and polymerized poly(ethylene glycol) dimethyl acrylate-modified β-cyclodextrin (CD) with ferrocene (Fc)-connected (S) (+)-camptothecin (CPT) (designated as MA-CD/Fc-CPT NPs). The as-prepared negatively charged supramolecular NPs can be taken up by tumor cells successfully owing to their reversible negative-to-positive charge transition capacity at acidic pH. The supramolecular NPs increased ROS generation and decreased GSH to amplify oxidative stress and improve the therapeutic effect of chemotherapy. As expected, MA-CD/Fc-CPT NPs displayed good drug delivery capabilities to tumor cells or tissues. MA-CD/Fc-CPT NPs also inhibited cancer cell proliferation in both the cells and tissues. This result was partially due to increased ROS generation and decreased GSH, which contributed to more pronounced oxidative stress. The as-prepared supramolecular NPs displayed great biosafety to normal tissues. According to our results, negatively charged supramolecular MA-CD/Fc-CPT NPs are well-suited for drug delivery and improved cancer treatment in TMEs.

Synthesis and Characterization of Cyclodextrin-Based Scaffold Incorporating Ciprofloxacin Antibacterial Agent for Skin Infection Prevention

The treatment of skin infections is one of the most challenging conditions in these days. Clinically most health professionals recommend the antibiotics; however, their efficiency is questionable due to their side effects, as well as their drug delivery capabilities. This work focuses on the noninvasive skin application of the Ciprofloxacin HCL (CFx)-loaded β-Cyclodextrin composite to suppress the antibacterial infections. Silk fibroins are used to enhance the mechanical properties, sodium alginate for dressing properties, while citric acid has been used as a linking agent. Combination of these forms a green composite, which is biocompatible and demonstrates better controlled drug-releasing properties. Four composites are made with different ratios of biocomponents. The composites are characterized by different characterization methods including Fourier transform infrared spectroscopy (FTIR) analysis, scanning electron microscopy (SEM), and electron-dispersive X-ray spectroscopy (EDX) to observe the surface and chemical properties of the composite scaffold. The antibacterial effect of the scaffold was observed through the agar diffusion test method. The results demonstrated that higher the ratio of β-Cyclodextrin, the larger will be the inhibition zone while other materials have limited to no effect of inhibition zone. The characterization tests show a successful bonding and loading of the CFx in the composite. Therefore, β-Cyclodextrin-based green composite scaffolds could be a promising candidate for wound dressing applications with low side effects.

Low temperature hybrid 3D printing of hierarchically porous bone tissue engineering scaffolds with in situ delivery of osteogenic peptide and mesenchymal stem cells

Compared to other conventional scaffold fabrication techniques, three-dimensional (3D) printing is advantageous in producing bone tissue engineering scaffolds with customized shape, tailored pore size/porosity, required mechanical properties and even desirable biomolecule delivery capability. However, for scaffolds with a large volume, it is highly difficult to get seeded cells to migrate to the central region of the scaffolds, resulting in an inhomogeneous cell distribution and therefore lowering the bone forming ability. To overcome this major obstacle, in this study, cell-laden bone tissue engineering scaffolds consisting of osteogenic peptide (OP) loaded β-tricalcium phosphate (TCP)/poly(lactic-co-glycolic acid) (PLGA) (OP/TCP/PLGA, designated as OTP) nanocomposite struts and rat bone marrow derived mesenchymal stem cell (rBMSC)-laden gelatin/GelMA hydrogel rods were produced through ‘dual-nozzle’ low temperature hybrid 3D printing. The cell-laden scaffolds exhibited a bi-phasic structure and had a mechanical modulus of about 19.6 MPa, which was similar to that of human cancellous bone. OP can be released from the hybrid scaffolds in a sustained manner and achieved a cumulative release level of about 78% after 24 d. rBMSCs encapsulated in the hydrogel rods exhibited a cell viability of about 87.4% right after low temperature hybrid 3D printing and could be released from the hydrogel rods to achieve cell anchorage on the surface of adjacent OTP struts. The OP released from OTP struts enhanced rBMSCs proliferation. Compared to rBMSC-laden hybrid scaffolds without OP incorporation, the rBMSC-laden hybrid scaffolds incorporated with OP significantly up-regulated osteogenic differentiation of rBMSCs by showing a higher level of alkaline phosphatase expression and calcium deposition. This ‘proof-of-concept’ study has provided a facile method to form cell-laden bone tissue engineering scaffolds with not only required mechanical strength, biomimetic structure and sustained biomolecule release profile but also excellent cell delivery capability with uniform cell distribution, which can improve the bone forming ability in the body.

What Do They Want? The Effect of Logistics Quality on Direct-to-Consumer Customer Satisfaction

Direct to consumer (D2C) business models, characterized by firms that design, source, and sell products directly to consumers bypassing traditional retail channels, are a relatively new phenomenon. One aspect we know little about is under what conditions consumers are willing to utilize a D2C channel, specifically, the degree to which the logistic service quality and information quality of user experience matter in choice of channel. Moreover, as these firms directly compete with Amazon’s delivery capability, we need to ask to what extent the so called “Amazon effect” impacts customer expectations. This study addresses these questions by conducting a scenario-based experiment which evaluates the effect of logistics service quality (LSQ) and online user experience (OUX) on customer satisfaction (CS), as moderated by price relative to Amazon (PRA). We find that LSQ has the largest positive effect on customer satisfaction, followed by OUX. Price moderates negatively (lessens) the effect of LSQ on customer satisfaction. Paradoxically, price also moderates the effect of OUX on CS, but counter-intuitively, strengthens it. The findings are reviewed in light of the so-called “Amazon effect”, the tendency of consumers to set their expectations for logistics at the levels of performance consistently provided by Amazon.com. Potential implications of the findings for the further evolution and growth of the D2C industry are presented.

Seamless Capacitive Body Channel Wireless Power Transmission Toward Freely Moving Multiple Animals in an Animal Cage.

Unstable wireless power transmission toward multiple living animals in an animal cage is one of the significant barriers to performing long-term and real-time neural monitoring in preclinical research. Here, seamless capacitive body channel (SCB) wireless power transmission (WPT) along with power management integrated circuit (PMIC) is designed using a standard 65 nm CMOS process. The SCB WPT enables stable wireless power transmission toward multiple 35 mm×20 mm×2 mm sized receivers (RXs) attached to freely moving animals in a 600 mm×600 mm×120 mm sized animal cage. By utilizing fringe-field capacitance and a body channel for wireless power link between the cage and RXs, the maximum difference in all measured power efficiencies in diverse scenarios is only 6.66 % with a 20 mW load. Even with a 90 ° RX rotation against the cage, power efficiency marks 17.76 %. Furthermore, an in-vivo experiment conducted with three untethered rats demonstrates the capability of continuous long-term power delivery in practical situations.

Importance of clinical research for the UK's 10-year cancer plan.

The ambition of the UK Government's 10-year cancer plan consultation document to transform cancer outcomes is highly welcome. 1 UK Department of Health and Social Care10-Year Cancer Plan: call for evidence. https://www.gov.uk/government/consultations/10-year-cancer-plan-call-for-evidence/10-year-cancer-plan-call-for-evidenceDate: March 31, 2022 Date accessed: May 27, 2022 Google Scholar This consultation must reflect on the extraordinary role played by the UK research community in responding to COVID-19—a response enabled by clinical research delivery infrastructure embedded within the National Health Service (NHS), which allowed rapid clinical evaluation of novel treatments and vaccines to save and transform lives. This unique national research delivery capability is the legacy of more than two decades of national clinical research networks, with co-operation between government agencies, charitable funders, and many others. This national capability started in cancer with the inception of the National Cancer Research Network and the National Cancer Research Institute (NCRI) in 2001. Now, through the National Institute for Health and Care Research (NIHR) Clinical Research Network (CRN), it extends across the full spectrum of health and social care. Cancer outcomes have been radically improved during this time, but further gains will require reinvigoration and realignment of our research capability at multiple levels, starting with the health-care workforce.

B2B buyer operational capability for the effective delivery of technology-enabled services in a multi-facility context

B2B buyer operational capability for the effective delivery of technology-enabled services in a multi-facility context

Green synthesis of oxidized starch with a novel catalyst based on Fe3O4 nanoparticles and H2O2 reagent to form thermoplastic as a stable gel coating on the cardiovascular stents

Oxidation of starch is one of the most commonly used approaches to improve its properties in the thermoplastic (TP) reactions. Iron oxide nanoparticle (IONP) (8.2 ± 1.5 nm) was used as a novel catalyst for this reaction. The functional groups of the carbonyl (COH) and the carboxyl (COOH) were obtained about of 7–12.2 % and 0.03–0.3 %. TP reaction and then electrospray technique of oxidized starch were used for the thin-film coating. The swelling ratio of the gelled thermoplastic structure with IONP (198 ± 9 % at 180 min) was lower than the sample without NP (193 ± 8 % at 90 min). The results from fourier transform infrared spectroscopy (FTIR), hydrogen nuclear magnetic resonance (HNMR), X-ray diffraction (XRD), and transmission electron microscopy (TEM) reveal desirable chemical and crystalline changes. Scanning electron microscopy (SEM) analysis was used to determine the thickness of the thin film (1.4 ± 0.2 μm) and the size of the electrosprayed droplets (172 ± 45 nm). Cytotoxicity studies of HUVEC and L929 cell lines against the extracts have shown appropriate biocompatibility. The blood compatibility analysis demonstrated proper results for (nanocomposite) NC. The results show that NC coated on metal surfaces can be used in medical approaches with drug delivery capability.

B16F10 Cell Membrane-Based Nanovesicles for Melanoma Therapy Are Superior to Hyaluronic Acid-Modified Nanocarriers.

Some cancer cell membrane (CCM)-derived nanovesicles show strong homing effects and are used for targeted cancer therapy. By co-constructing the B16F10 cell membrane with a PEGylated phospholipid membrane, a new nanocarrier with a composite nanocrown structure was developed, which can evade immune recognition and actively target homologous melanoma. The nanocrowns have an encapsulation efficiency of more than 90% for paclitaxel and showed no significant difference (p > 0.05) from the PEGylated phospholipid membrane vesicles. Compared with the hyaluronic acid-modified PEGylated phospholipid membrane vesicles, the biomimetic nanocrowns enhanced the escape of nanovesicles from reticuloendothelial cells in vitro and extended the circulation time in vivo; moreover, the nanocrowns showed superior melanoma-targeted drug delivery capability and improved anticancer effects of paclitaxel as demonstrated by the inhibition of B16F10 cell proliferation and induction of apoptosis by interfering with microtubule formation. In contrast, the modification of hyaluronic acid did not increase the targeting capacity or antitumor effects of the nanocrowns, confirming that the superior targeting capacity was mediated by the exposed homologous CCMs rather than by hyaluronic acid. Our results demonstrate the potential of using biomimetic nanocrowns for active melanoma-targeted therapy.

Self-Assembled ATP-Responsive DNA Nanohydrogel for Specifically Activated Fluorescence Imaging and Chemotherapy in Cancer Cells.

Tumor marker-responsive drug delivery systems have been developed for cancer imaging and chemotherapy. However, improving their ability of controlled drug release remains a challenge. In this study, we have developed an adenosine triphosphate (ATP)-responsive DNA nanohydrogel for specifically activated fluorescence imaging and chemotherapy in cancer cells. Acrylamide and acrydite-modified DNAs were polymerized to obtain DNA-grafted polyacrylamide copolymers. Then, the copolymers acted as the backbone of the nanohydrogel and were assembled by base complementation with ATP aptamer linkers to construct an ATP-responsive nanohydrogel. Meanwhile, the chemotherapeutic drug doxorubicin (DOX) was added and loaded into the ATP-responsive nanohydrogel during the assembly process. After endocytosis by cancer cells and response to a high intracellular ATP level, the DOX-loaded nanohydrogel disassembled due to the formation of aptamer/ATP complexes. Subsequently, the released DOX played a role in fluorescence imaging and chemotherapy of cancer cells. Through the ATP-responsive property and satisfying drug delivery capability, this nanohydrogel realized fluorescence imaging and specific cancer cell killing capabilities due to different intracellular ATP levels in normal and cancer cell lines. In summary, this study has provided a novel strategy of constructing a tumor microenvironment-responsive drug delivery system triggered by the tumor markers for tumor intracellular imaging and chemotherapy.

An International Core Capability Framework for Physiotherapists to Deliver Quality Care via Videoconferencing: A Delphi Study

Background The provision of physiotherapy care via telehealth is becoming increasingly common and, in some circumstances, is a necessity, as observed during the COVID-19 pandemic. Therefore, it is important to understand what are the core capabilities that physiotherapists need in order to deliver quality care via videoconferencing. Objective The objective of our study was to develop a discipline-specific core capability framework for physiotherapists to deliver quality care via videoconferencing. Methods An international Delphi panel comprising a steering group and experts in the field, including physiotherapy researchers, physiotherapy clinicians, representatives of physiotherapy organizations, and consumers, was established by drawing on the research team’s academic, research, and clinical networks as well as contacting international physiotherapy organizations. The draft framework was developed by the research team and steering group, based on relevant documents identified within the literature. The panel considered a draft framework of 73 specific capabilities mapped across 8 domains. Over 3 rounds, panelists rated their agreement (Likert or numerical rating scales) on whether each capability was essential (core) for physiotherapists to deliver quality care via videoconferencing. The capabilities that achieved consensus, defined as 75% of the panel ratings being ≥7 out of 10 in round 3, were retained. Results A total of 130 panelists from 32 countries participated in round 1, with retention rates of 65% and 60% in rounds 2 and 3, respectively. The final framework comprised 60 capabilities across the following seven domains: compliance (capabilities: n=7), patient privacy and confidentiality (capabilities: n=4), patient safety (capabilities: n=7), technology skills (capabilities: n=7), telehealth delivery (capabilities: n=16), assessment and diagnosis (capabilities: n=7), and care planning and management (capabilities: n=12). Conclusions This framework outlines the specific core capabilities that are required of physiotherapists to provide quality care via videoconferencing. The core capability framework provides guidance for physiotherapists to deliver care via videoconferencing and will help inform the future development of physiotherapy curricula and professional development initiatives in the delivery of telehealth. Acknowledgments The members of the International Videoconferencing Steering Group are Michael Billings, Carmen Cooper-Oguz, Karen Finnan, Sarah Gallagher, Daniel Kenneth Gilbertson, Lesley Holdsworth, Anne Holland, Jeremey McAlister, Dan Miles, and Robin Rots. Conflict of Interest No conflicts declared.

Averrhoa carambola extractive inhibits breast cancer via regulating CEPT1 and LYPLA1

Liposomes have been widely exploited as a drug delivery system in treating tumors because of their advantage to enhance anti-tumor efficacy and reduce side effects. In this study, the tumor-targeted 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4‑dione (DMDD, i.e., Averrhoa carambola extractive) liposomes (HA/TN-DLP) were conducted and assessed. HA/TN-DLP showed controllable drug loading (up to 83%) with high stability. In vitro and in vivo studies showed good cell uptake behavior and high inhibition rate of breast cancer compared to free DMDD. HA/TN-DLP might be the suitable for DMDD due to its better advantages in delivery, penetrability, and targeting-tumor capability. For in vivo mouse model tests, HA/TN-DLP effectively inhibited tumor growth compared to free DMDD. Further analyses indicated that HA/TN-DLP inhibited the glycerophospholipid metabolism pathway by reducing the biosynthesis of phosphatidylcholine and 1-acyl-sn‑glycero-3-phosphocholine through regulating the expressions of CEPT1 and LYPLA1, and inhibited tumor cell growth by regulating the PI3K/Akt and NF-κB signaling pathways. In conclusion, the obviously enhanced antitumor effect further demonstrated that HA/TN-DLP may be a promising tumor-targeting agent.

Efficiency gains in public service delivery through information technology in municipalities

According to public management theory and existing research on information technology (IT) value creation in the public sector, governments should actively strive to generate greater public value with IT, and the capability of public service delivery is at the center of this public value. In this study, we focus on efficiency gains in public service delivery through IT in municipal governments. First, we answer the research question: How much euro efficiency is gained in public service delivery by €1 increase in share of IT costs relative to total municipal costs? Second, we focus on contextual effects of these efficiency gains, by analyzing the effects of workforce mean age, workforce age dispersion and training costs. We use data from Dutch municipalities and study these efficiency gains in the period 2014–2018. Our empirical strategy encompasses a two-step procedure combining a stochastic frontier model and ordinary least squares models. Our analysis suggests that share of IT costs relative to total municipal costs (in short: share of IT costs) can explain efficiency in public service delivery by municipalities. Our results indicate that an increase of €1 in favour of share of IT costs leads to a net cost efficiency gain of €1.08. We also show that this effect in efficiency gains diminishes with a higher share of IT costs. Our results also show that workforce mean age, workforce age dispersion and training costs do not influence the relation between share of IT costs and efficiency.

Digitalization in the Land Service Delivery: Comparison between Bangladesh and Indonesia

The administration of a country's land system has a major impact on its economy and society. Digital land management has the potential to improve the land administration of developing countries and make it more efficient. The governments of Bangladesh and Indonesia have implemented a digital land management framework in the land system to ensure optimal land development, in particular, to deliver land services efficiently. The land offices of both countries have a variety of obstacles when it comes to delivering digital services. Because of this, it is important to recognize the current use of digitalization and identify the variables influencing digitalization in land service delivery by land offices in order to make informed decisions about their future. Content analysis was applied to gather data for the study, which used a qualitative approach. The correct deployment of digitization in land administration in both nations is being slowed down by a lack of institutional and operational capability and personnel misconduct in service delivery.

Fluorescent carbon dots with real-time nucleolus-monitoring capability for gene delivery and biosensing of NO2– and pH

To achieve gene therapy, DNA, one of the most commonly used therapeutic nucleic acids, is typically employed to transfer into the nucleous. However, it remains extremely challenging to seek vectors with high transfection efficiency and low toxicity to introduce DNA into the nucleolus. Herein, we have designed and developed green fluorescent carbon dots (G-CDs) for nucleolus targeting, gene delivery, and biosensing of NO2– and pH. G-CDs were synthesized by a simple hydrothermal mean using 3,5-diaminobenzoic acid and citric acid as precursors. As-prepared G-CDs not only possess bright green fluorescence with respectable fluorescence quantum yield of 41%, but also exhibit low cytotoxicity and superior biocompatibility. Interestingly, G-CDs display accurate nucleolus targeting characteristic due to the response of G-CDs to DNA in the nucleolus. More unexpectedly, G-CDs could effectively deliver exogenous ROX-labelled DNA into the nucleolus of HeLa cells, which is the first time that fluorescent CDs are used as nanocarriers to transfer DNA to nucleolus. What’s more, G-CDs have been expanded to visually monitor NO2– and pH fluctuations in living cells.

Rational Design of Multifunctional CuS Nanoparticle‐PEG Composite Soft Hydrogel‐Coated 3D Hard Polycaprolactone Scaffolds for Efficient Bone Regeneration

Abstract3D‐printed polycaprolactone (PCL) scaffolds have been extensively studied for application in bone tissue engineering. However, PCL‐based scaffolds with enhanced bioactivity and intelligent delivery capability for bone repair remains challenging. Herein, CuS nanoparticle‐PEG soft hydrogel‐coated 3D hard polycaprolactone scaffolds (denoted as CuS‐PEG‐PCL scaffold) are rationally designed for efficient bone regeneration. CuS nanoparticles cross‐linked PEG hydrogel (CuS‐PEG‐hydrogel) endows the PCL‐based scaffold with excellent photothermal properties and stable soft elasticity, while the PCL scaffold provides excellent mechanical performance. Upon exposure to 1064 nm near‐infrared (NIR) light irradiation, dexamethasone sodium phosphate (Dexp), stored in the CuS‐PEG‐PCL scaffold, can be controllably released, which efficiently promotes osteogenic differentiation of bone mesenchymal stem cells (BMSCs). In addition, the combination of mild heating at 42 ± 0.5 °C further promoted osteogenic differentiation of BMSCs. Subsequently, this Dexp‐loaded CuS‐PEG‐PCL scaffold (D‐CuS‐PEG‐PCL scaffold) with NIR light treatment at the tibial defect of rats presented the highest bone regeneration capacity. These findings demonstrate that the Dexp‐loaded CuS‐PEG‐hydrogel can effectively modify the 3D printed PCL scaffold. Therefore, this multifunctional scaffold with a soft‐hard hybrid structure has the potential to become an advanced drug delivery vehicle in the treatment of large bone defects.

Hybrid MCDM Solutions for Evaluation of the Logistics Performance Index of the Western Balkan Countries

Abstract The Logistics Performance Index (LPI) performed by the World Bank is an indicator of the logistics environment quality of a country in which logistics operators act. The LPI is an interactive tool designed to help countries identify challenges, innovative solutions, and opportunities they face in their work in the field of trade and logistics. The aim of this paper is to conduct a comparative analysis and ranking of the LPI of the countries in the Western Balkans (Bosnia and Herzegovina, North Macedonia, Albania, Serbia and Montenegro), calculated by the World Bank for 2018, using an integrated Criteria Importance Through Intercriteria Correlation (CRITIC)-Measurement Alternatives and Ranking according to Compromise Solution (MARCOS) model and thus show the real picture of the logistics environment. In order to determine the performance of countries and show the overall logistics performance, six key dimensions are used: customs, infrastructure, international transport, logistics capability, tracking and tracing of goods and shipment delivery within scheduled or expected times. Using the CRITIC method, the weight values of the previously mentioned six criteria were calculated, whereby the criterion related to shipment delivery within scheduled times was singled out as the most significant criterion. Then, by applying the MARCOS method, the countries of the Western Balkans were ranked on the basis of the six defined criteria. Based on the results obtained, the best-ranked country is Serbia. The analysis of the sensitivity of the results to changes in the significance of the criteria does not show significant changes in the ranking.

Experimentally Validated Extended Kalman Filter Approach for Geomagnetically Induced Current Measurement

Geomagnetically induced currents (GICs) are referred to as the quasi-dc current flows in power networks, driven by complex space weather-related phenomena. Such currents are a potential threat to the power delivery capability of electrical grids. To mitigate the detrimental impacts of GICs on critical infrastructures, the GICs should be monitored in power systems. Being inherently dc from the power frequency point of view, the components of GICs are, however, challenging and costly to monitor in ac power grids. This article puts forward a novel methodology for the real-time estimation of GICs in power transformers. Such aim is attained by means of an extended Kalman filter (EKF)-based approach, mounted on the nonlinear state-space model of the transformer, whose parameters can be derived from standard tests. The proposed EKF-based algorithm employs the available measurements for the transformer differential protection. The proposed approach, relying on the differential current, can properly deal with the external sources of interference like harmonic excitation and loading. The EKF-based estimator presented is validated by simulation and experimental data. The results verify the ability of the proposed approach to robustly estimate the GIC level during various operating conditions.

Exploring the Nexus Between E-Business Processes and Organizational Performance: Can Technological Opportunism Play Any Role?

The digitization of business processes has gained much scholarly and practical attention in the recent past. To understand their effectiveness, particularly in connection to organizational performance, the current study developed and tested a comprehensive framework. Through obtaining data from 350 manufacturing businesses, the study investigated using Smart PLS3 and found a significant influence of online procurement, channel management, and service delivery capabilities on organizational performance. Furthermore, the study also found the significant direct and moderating potential of technological opportunism to harness organizational performance. The study concludes that e-business processes serve as crucial resources and capabilities for businesses to achieve their goals and objectives. The study offers contributory implications for theory and practice indicating for strategic investment of e-business processes for businesses aiming to boost their performance.