ACS Applied Nano Materials最新文献

Co-delivery strategies have become an integral active delivery approach, although understanding of how the microstructural characteristics could be deployed to achieve independently regulated active co-delivery profiles, is still an area at its infancy. Herein, the capacity to provide such control was explored by utilizing Pickering emulsions stabilized by lipid particles, namely solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). These dual functional species, regarding their concurrent Pickering stabilization and active carrying/delivery capabilities, were formulated with different solid lipid and surfactant types, and the effect on the release and co-release modulation of two hydrophobic actives separately encapsulated within the lipid particles themselves and within the emulsion droplets was investigated. Disparities between the release profiles from the particles in aqueous dispersions or at an emulsion interface, were related to the specific lipid matrix composition. Particles composed of lipids with higher oil phase compatibility of the emulsion droplets were shown to exert less control over their release regulation ability, as were particles in the presence of surfactant micelles in the continuous phase. Irrespective of their formulation characteristics, all particles provided a level of active release control from within the emulsion droplets, which was dependant on the permeability of the formed interfacial layer. Specifically, use of a bulkier particle surfactant or particle sintering at the droplet interface resulted in more sustained droplet release rates. Compared to sole release, the co-release performance remained unaffected by the co-existence of the two hydrophobic actives with the co-release behavior persisting over a storage period of 1 month.

In online adaptive radiotherapy (ART), quick computation-based secondary dose verification is crucial for ensuring the quality of ART plans while the patient is positioned on the treatment couch. However, traditional dose verification algorithms are generally time-consuming, reducing the efficiency of ART workflow. This study aims to develop an ultra-fast deep-learning (DL) based secondary dose verification algorithm to accurately estimate dose distributions using computed tomography (CT) and fluence maps (FMs). We integrated FMs into the CT image domain by explicitly resolving the geometry of treatment delivery. For each gantry angle, an FM was constructed based on the optimized multi-leaf collimator apertures and corresponding monitoring units. To effectively encode treatment beam configuration, the constructed FMs were back-projected to $30$ cm away from the isocenter with respect to the exact geometry of the treatment machines. Then, a 3D U-Net was utilized to take the integrated CT and FM volume as input to estimate dose. Training and validation were performed on $381$ prostate cancer cases, with an additional $40$ testing cases for independent evaluation of model performance. The proposed model can estimate dose in ∼ $15$ ms for each patient. The average γ passing rate ( $3\%/2\text{mm}$ , $10\%$ threshold) for the estimated dose was 99.9% ± 0.15% on testing patients. The mean dose differences for the planning target volume and organs at risk were $0.07\%\pm 0.34\%$ and $0.48\%\pm 0.72\%$ , respectively. We have developed a geometry-resolved DL framework for accurate dose estimation and demonstrated its potential in real-time online ART doses verification.

Cancer has agonized the human race for millions of years. The present decade witnesses biological therapeutics to combat cancer effectively. Cancer Immunotherapy involves the use of therapeutics for manipulation of the immune system by immune agents like cytokines, vaccines, and transfection agents. Recently, this therapeutic approach has got vast attention due to the current pandemic COVID-19 and has been very effective. Concerning cancer, immunotherapy is based on the activation of the host's antitumor response by enhancing effector cell number and the production of soluble mediators, thereby reducing the host's suppressor mechanisms by induction of a tumour killing environment and by modulating immune checkpoints. In the present era, immunotherapies have gained traction and momentum as a pedestal of cancer treatment, improving the prognosis of many patients with a wide variety of haematological and solid malignancies. Food supplements, natural immunomodulatory drugs, and phytochemicals, with recent developments, have shown positive trends in cancer treatment by improving the immune system. The current review presents the systematic studies on major immunotherapeutics and their development for the effective treatment of cancers as well as in COVID-19. The focus of the review is to highlight comparative analytics of existing and novel immunotherapies in cancers, concerning immunomodulatory drugs and natural immunosuppressants, including immunotherapy in COVID-19 patients.

Microneedle (MN) delivery devices are more accepted by people than regular traditional needle injections (e.g. vaccination) due to their simplicity and adaptability. Thus, patients of chronic diseases like diabetes look for alternative pain-free treatment regimens circumventing regular subcutaneous injections. Insulin microneedles (INS-MNs) are a thoughtfully researched topic (1) to overcome needle phobia in patients, (2) for controlled delivery of the peptide, (3) decreasing the frequency of drug administration, (4) to ease the drug administration procedure, and (5) thus increasing patient adherence to the treatment dosage regimes. MNs physically disrupt the hard outer skin layer to create minuscule pores for insulin (INS) to pass through the dermal capillaries into the systemic circulation. Biodegradable polymeric MNs are of greater significance for INS and vaccine delivery than silicon, metal, glass, or non-biodegradable polymeric MNs due to their ease of fabrication, mass production, cost-effectiveness, and bioerodability. In recent years, INS-MNs have been researched to deliver INS through the transdermal implants, buccal mucosa, stomach wall, intestinal mucosal layers, and colonic mucosa apart from the usual transdermal delivery. This review focuses on the design characteristics and the applications of biodegradable/dissolvable polymeric INS-MNs in transdermal, intra-oral, gastrointestinal (GI), and implantable delivery. The prospective approaches to formulate safe, controlled-release INS-MNs were highlighted. Biodegradable/dissolvable polymers, their significance, their impact on MN morphology, and INS release characteristics were outlined. The developments in biodegradable polymeric INS-MN technology were briefly discussed. Bio-erodible polymer selection, MN fabrication and evaluation factors, and other design aspects were elaborated.

The local injection of therapeutic drugs, including cells, oncolytic viruses and nucleic acids, into different organs is an administrative route used to achieve high drug exposure at the site of action. However, after local injection, material backflow and side effect reactions can occur. Hence, this study was carried out to investigate the effect of gelatin on backflow reduction in local injection. Gelatin particles (GPs) and hydrolyzed gelatin (HG) were injected into tissue models, including versatile training tissue (VTT), versatile training tissue tumor-in type (VTT-T), and broiler chicken muscles (BCM), using needle gauges between 23 G and 33 G. The backflow material fluid was collected with filter paper, and the backflow fluid rate was determined. The backflow rate was significantly reduced with 35 μm GPs (p value < .0001) at different concentrations up to 5% and with 75 μm GPs (p value < .01) up to 2% in the tissue models. The reduction in backflow with HG of different molecular weights showed that lower-molecular-weight HG required a higher-concentration dose (5% to 30%) and that higher-molecular-weight HG required a lower-concentration dose (7% to 8%). The backflow rate was significantly reduced with the gelatin-based formulation, in regard to the injection volumes, which varied from 10 μL to 100 μL with VTT or VTT-T and from 10 μL to 200 μL with BCM. The 35 μm GPs were injectable with needles of small gauges, which included 33 G, and the 75 μm GPs and HG were injectable with 27 G needles. The backflow rate was dependent on an optimal viscosity of the gelatin solutions. An optimal concentration of GPs or HG can prevent material backflow in local injection, and further studies with active drugs are necessary to investigate the applicability in tumor and organ injections.

Special Series: Leading Women in Respiratory Clinical Sciences Series Editors: Anne-Marie Russell and Kathleen O Lindell See related Letter.

Burn injuries can result in a significant inflammatory response, often leading to hypertrophic scarring (HTS). Local drug therapies e.g. corticoid injections are advised to treat HTS, although they are invasive, operator-dependent, extremely painful and do not permit extended drug release. Polymer-based microneedle (MN) arrays can offer a viable alternative to standard care, while allowing for direct, painless dermal drug delivery with tailorable drug release profile. In the current study, we synthesized photo-crosslinkable, acrylate-endcapped urethane-based poly(ε-caprolactone) (AUP-PCL) toward the fabrication of MNs. Physico-chemical characterization (¹H-NMR, evaluation of swelling, gel fraction) of the developed polymer was performed and confirmed successful acrylation of PCL-diol. Subsequently, AUP-PCL, and commercially available PCL-based microneedle arrays were fabricated for comparative evaluation of the constructs. Hydrocortisone was chosen as model drug. To enhance the drug release efficiency of the MNs, Brij®35, a nonionic surfactant was exploited. The thermal properties of the MNs were evaluated via differential scanning calorimetry. Compression testing of the arrays confirmed that the MNs stay intact upon applying a load of 7 N, which correlates to the standard dermal insertion force of MNs. The drug release profile of the arrays was evaluated, suggesting that the developed PCL arrays can offer efficient drug delivery for up to two days, while the AUP-PCL arrays can provide a release up to three weeks. Finally, the insertion of MN arrays into skin samples was performed, followed by histological analysis demonstrating the AUP-PCL MNs outperforming the PCL arrays upon providing pyramidical-shaped perforations through the epidermal layer of the skin.

Potassium (K⁺) is indispensable for the regulation of a plethora of functions like plant metabolism, growth, development, and abiotic stress responses. K⁺ is associated with protein synthesis and entangled in the activation of scores of enzymes, stomatal regulation, and photosynthesis. It has multiple transporters and channels that assist in the uptake, efflux, transport within the cell as well as from soil to different tissues, and the grain filling sites. While it is implicated in ion homeostasis during salt stress, it acts as a modulator of stomatal movements during water deficit conditions. K⁺ is reported to abate the effects of chilling and photooxidative stresses. K⁺ has been found to ameliorate effectively the co-occurrence of drought and high-temperature stresses. Nutrient deficiency of K⁺ makes leaves necrotic, leads to diminished photosynthesis, and decreased assimilate utilization highlighting the role it plays in photosynthesis. Notably, K⁺ is associated with the detoxification of reactive oxygen species (ROS) when plants are exposed to diverse abiotic stress conditions. It is irrefutable now that K⁺ reduces the activity of NADPH oxidases and at the same time maintains electron transport activity, which helps in mitigating the oxidative stress. K⁺ as a macronutrient in plant growth, the role of K⁺ during abiotic stress and the protein phosphatases involved in K⁺ transport have been reviewed. This review presents a holistic view of the biological functions of K⁺, its uptake, translocation, signaling, and the critical roles it plays under abiotic stress conditions, plant growth, and development that are being unraveled in recent times.

Quinic acid is a cyclohexanecarboxylic acid contained in the extracts of several parts of medicinal plants including Haematocarpus validus, Hypericum empetrifolium, Achillea pseudoaleppica, Rumex nepalensis, Phagnalon saxatile subsp. saxatile, Coffea arabica, Ziziphus lotus L, and Artemisia annua L … etc. Currently, in vitro and in vivo pharmacological studies showed that quinic acid exhibits various biological activities, such as antioxidant, antidiabetic, anticancer activity, antimicrobial, antiviral, aging, protective, anti-nociceptive and analgesic effects. Indeed, QA possesses an important antibacterial effect which could be explained by the fact that this molecule modules the functions of ribosomes and the synthesis of aminoacyl-tRNAs, modifications the levels of glycerophospholipids and fatty acids and disruption of the oxidative phosphorylation pathway thereby causing interference with membrane fluidity. The antidiabetic activity of AQ is achieved by stimulation of insulin secretion via the mobilization of Ca2+ from intracellular reserves and the increase in the NAD(P)H/NAD(P)+ ratio. Its anticancer effect is through the promotion of apoptosis, inhibition of activator protein 1 (AP-1) and signaling pathways involving protein kinase C (PKC) and certain mitogen-activated protein kinases (MAPKs), resulting in the downregulation of matrix metallopeptidase 9 (MMP-9) expression. Therefore, this review describes the main research work carried out on the biological properties of AQ and the mechanism of action underlying some of these effects, as well as the investigations of the main pharmacokinetic studies.