Optimal Route Planning for Truck–Drone Delivery Using Variable Neighborhood Tabu Search Algorithm

The optimal delivery route problem for truck–drone delivery is defined as a traveling salesman problem with drone (TSP-D), which has been studied in a wide range of previous literature. However, most of the existing studies ignore truck waiting time at rendezvous points. To fill this gap, this paper builds a mixed integer nonlinear programming model subject to time constraints and route constraints, aiming to minimize the total delivery time. Since the TSP-D is non-deterministic polynomial-time hard (NP-hard), the proposed model is solved by the variable neighborhood tabu search algorithm, where the neighborhood structure is changed by point exchange and link exchange to expand the tabu search range. A delivery network with 1 warehouse and 23 customer points are employed as a case study to verify the effectiveness of the model and algorithm. The 23 customer points are visited by three truck–drones. The results indicate that truck–drone delivery can effectively reduce the total delivery time by 20.1% compared with traditional pure-truck delivery. Sensitivity analysis of different parameters shows that increasing the number of truck–drones can effectively save the total delivery time, but gradually reduce the marginal benefits. Only increasing either the truck speed or drone speed can reduce the total delivery time, but not to the greatest extent. Bilateral increase of truck speed and drone speed can minimize the delivery time. It can clearly be seen that the proposed method can effectively optimize the truck–drone delivery route and improve the delivery efficiency.

The tetraspanin TSPAN5 regulates AMPARs exocytosis by interacting with the AP-4 complex

Intracellular trafficking of AMPA receptors is a tightly regulated process which involves several adaptor proteins, and is crucial for the activity of excitatory synapses in both basal conditions and during synaptic plasticity. We found that, in rat hippocampal neurons, an intracellular pool of the tetraspanin TSPAN5 specifically promotes exocytosis of newly synthesised GluA2-containing AMPA receptors without affecting their internalisation. TSPAN5 mediates this function by interacting with AP-4 and Stargazin and possibly using recycling endosomes as a delivery route. This work highlights TSPAN5 as a new adaptor regulating AMPA receptor trafficking. In addition, it provides a possible mechanism for the intellectual disability symptoms that occur in AP-4 deficiency syndrome.

Intranasal Drug Delivery: Novel Delivery Route for Management of Parkinson’s and Depression Neurological Disorders

Neurological disorders are increasing worldwide due to the rapidly aging population, which increases healthcare costs. Drug delivery to the brain is challenging because of the brain's anatomy, and orally administered drugsare mostly unable to cross BBB. Intranasal (Nose to Brain) administration of drugs is one novel approach to address this challenge. Intranasal delivery has appeared to evade the blood-brain barrier (BBB) and deliver the drug into the CNS at a higher rate and degree than another traditional route. Transport of drugs from the nasal cavity to the brain along with olfactory and trigeminal nerves. The purpose of this review is drug delivery by the intranasal route for treating neurological disorders like Parkinson’s and depression because drug delivery by other routes is unable to cross BBB. Still, delivery through the intranasal route by using the nanotechnology approach is possible to deliver the drug directly to CNS.

Persistency of Mesenchymal Stromal/Stem Cells in Lungs

Mesenchymal stromal/stem cells (MSCs) are a fibroblast-like cell population with high regenerative potential that can be isolated from many different tissues. Several data suggest MSCs as a therapeutic tool capable of migrating to a site of injury and guide tissue regeneration mainly through their secretome. Pulmonary first-pass effect occurs during intravenous administration of MSCs, where 50 to 80% of the cells tend to localize in the lungs. This phenomenon has been exploited to study MSC potential therapeutic effects in several preclinical models of lung diseases. Data demonstrated that, regardless of the lung disease severity and the delivery route, MSCs were not able to survive longer than 24 h in the respiratory tract but still surprisingly determined a therapeutic effect. In this work, two different mouse bone marrow-derived mesenchymal stromal/stem cell (mBM-MSC) lines, stably transduced with a third-generation lentiviral vector expressing luciferase and green fluorescent protein reporter genes tracking MSCs in vivo biodistribution and persistency, have been generated. Cells within the engrafted lung were in vivo traced using the high-throughput bioluminescence imaging (BLI) technique, with no invasiveness on animal, minimizing biological variations and costs. In vivo BLI analysis allowed the detection and monitoring of the mBM-MSC clones up to 28 days after implantation independently from the delivery route. This longer persistency than previously observed (24 h) could have a strong impact in terms of pharmacokinetics and pharmacodynamics of MSCs as a therapeutic tool.

Current State and Future Directions of Intranasal Delivery Route for Central Nervous System Disorders: A Scientometric and Visualization Analysis

Background: The management of various central nervous system (CNS) disorders has been challenging, due to highly compact blood-brain barrier (BBB) impedes the access of most pharmacological agents to the brain. Among multiple strategies proposed to circumvent this challenge, intranasal delivery route has sparked great interest for brain targeting in the past decades. The aim of this study was to apply scientometric method to estimate the current status and future trends of the field from a holistic perspective.Methods: All relevant publications during 1998–2020 were retrieved from the Web of Science Core Collection (SCIE, 1998-present). Two different scientometric software including VOS viewer and CiteSpace, and one online platform were used to conduct co-authorship, co-citation, and co-occurrence analysis of journals, countries, institutes, authors, references and keywords.Results: A total of 2,928 documents, including 2,456 original articles and 472 reviews, were retrieved. Our analysis revealed a significant increasing trend in the total number of scientific publications over the past 2 decades (R2 = 0.98). The United States dominated the field, reflecting in the largest amount of publications (971), the highest H-index (99), and extensive international collaboration. Jamia Hamdard contributed to most publications. Frey WH and Illum L were key researchers with the highest number of publications and citations, respectively. The International Journal of Pharmaceutics was the most influential academic journal, and Pharmacology/Pharmacy and Neurosciences/Neurology were the hottest research categories in this field. Based on keywords occurrence analysis, four main topics were identified, and the current research focus of this field has shifted from cluster 4 (pathways and mechanisms of intranasal delivery) to cluster 2 (the study of nasal drug delivery systems), especially the nanostructured and nano-sized carrier systems. Keywords burst detection revealed that the research focus on oxidative stress, drug delivery, neuroinflammation, nanostructured lipid carrier, and formulation deserves our continued attention.Conclusion: To the authors’ knowledge, this is the first scientometric analysis regarding intranasal delivery research. This study has demonstrated a comprehensive knowledge map, development landscape and future directions of intranasal delivery research, which provides a practical and valuable reference for scholars and policymakers in this field.