Lymphatic Uptake of Liposomes after Intraperitoneal Administration Primarily Occurs via the Diaphragmatic Lymphatics and is Dependent on Liposome Surface Properties.

Drugs are commonly administered via the intraperitoneal (IP) route to treat localized infections and cancers in patients and to test drug efficacy and toxicity in preclinical studies. Despite this, there remain large gaps in our understanding of drug absorption routes (lymph vs blood) and pharmacokinetics following IP administration. This is particularly true when drugs are administered in complex delivery systems such as liposomes which are the main marketed formulation for several drugs that are administered intraperitoneally. This study investigated the impact of liposome surface properties (charge and PEGylation) on absorption into lymph and blood, and lymphatic disposition patterns, following IP administration. To achieve this, stable 3H-dipalmitoyl-phosphatidylcholine (DPPC) and 14C-sucrose-radiolabeled liposomes of 100-150 nm diameter with negative, neutral, or positive surface charge, or a PEGylated surface, were prepared and administered intraperitoneally to rats. Radiolabel concentrations were measured in lymph, blood, and lymph nodes (LNs). Lymph was collected from the thoracic lymph duct at either the abdomen (ABD) or the jugular-subclavian junction (JSJ). The lymphatic recovery of the radiolabels was substantially lower after administration in positively charged compared to the neutral, negative, or PEGylated liposomes. Radiolabel recovery was substantially greater (up to 18-fold) in the thoracic lymph collected at the JSJ when compared to that at the ABD, suggesting that liposomes entered the lymphatics at the diaphragm. Consistent with this, the concentration of the liposome labels was substantially higher (up to seven-fold) in mediastinal than in mesenteric LNs. Overall, this study shows how the peritoneal absorption and lymphatic disposition of drugs administered intraperitoneally can be manipulated through a careful selection of the drug delivery system and may thus be optimized to treat localized conditions such as cancers, infections, inflammatory diseases, and acute and critical illness.

Structurally Aligned Multifunctional Neural Probe (SAMP) Using Forest-Drawn CNT Sheet onto Thermally Drawn Polymer Fiber for Long-Term In Vivo Operation.

Neural probe engineering is a dynamic field, driving innovation in neuroscience and addressing scientific and medical demands. Recent advancements involve integrating nanomaterials to improve performance, aiming for sustained in vivo functionality. However, challenges persist due to size, stiffness, complexity, and manufacturing intricacies. To address these issues, a neural interface utilizing freestanding CNT-sheets drawn from CNT-forests integrated onto thermally drawn functional polymer fibers is proposed. This approach yields a device with structural alignment, resulting in exceptional electrical, mechanical, and electrochemical properties while retaining biocompatibility for prolonged periods of implantation. This Structurally Aligned Multifunctional neural Probe (SAMP) employing forest-drawn CNT sheets demonstrates in vivo capabilities in neural recording, neurotransmitter detection, and brain/spinal cord circuit manipulation via optogenetics, maintaining functionality for over a year post-implantation. The straightforward fabrication method's versatility, coupled with the device's functional reliability, underscores the significance of this technique in the next-generation carbon-based implants. Moreover, the device's longevity and multifunctionality position it as a promising platform for long-term neuroscience research.

Development and Feasibility Test of a Mouth Contactless Breathing Exercise Solution Using Virtual Reality: A Randomized Crossover Trial.

PURPOSE: The purpose of this study was to develop a novel mouth contactless breathing exercise solution based on virtual reality (VR), and to test its feasibility. METHODS: We developed the Virtual Reality-based Breathing Exercise System (VR-BRES), a self-regulating biofeedback breathing exercise with gaming characteristics and a soft stretch sensor. The feasibility and efficacy of the VR-BRES prototype were investigated through a randomized crossover trial. Fifty healthy adults participated in the trial, and their respiratory parameters and user evaluation of the VR-BRES were compared with conventional deep breathing (CDB) exercises. RESULTS: The respiratory parameters, forced vital capacity (Z = 4.82, 4.95, p < .001), forced expiratory volume in one second (t = 6.02, 6.26, p < .001), and peak expiratory flow (t = 5.35, 5.68, p < .001) were significantly higher during breathing exercises using the VR-BRES. User evaluation was also significantly higher for the VR-BRES in terms of efficiency (Z = 3.86, p < .001), entertainingness (Z = 5.00, p < .001), and intention to use (Z = 3.22, p = .001) compared to CDB. However, there was no difference in convenience between the two methods (Z = -0.90, p = .369). CONCLUSION: The VR-BRES has the potential to be an efficient breathing exercise solution. We recommend a clinical study that evaluates the effects of the VR-BRES for a certain period of time for people who need breathing exercises.

Nucleic acid from saliva and salivary cells for noninvasive genotyping of Crohn's disease patients.

CARD15 genes carrying the 3020insC frameshift polymorphism encode a truncated CARD15 protein that is unresponsive to bacterial muramyl dipeptide, and are strongly associated with increased susceptibility to Crohn's disease (CD). In this study we established that CARD15 gene sequences encompassing the major 3020insC polymorphism could be readily amplified from the DNA found in saliva. In addition, CARD15 RNA sequences can be readily derived from the cellular component of saliva, which is primarily comprised of buccal epithelial cells. Our results demonstrate that saliva is a readily accessible source of DNA and RNA for genotyping CD patients for variants of the CARD15 gene, representing an alternative source of nucleic acid to that obtained from venous blood.