ABSTRACT
Non-Drug Intervention (NDI) is one of the important means to prevent and control the outbreak of coronavirus disease 2019 (COVID-19), and the implementation of this series of measures plays a key role in the development of the epidemic. The purpose of this paper is to study the impact of different mitigation measures on the situation of the COVID 19, and effectively respond to the prevention and control situation in the "post-epidemic era". The present work is based on the Susceptible-Exposed-Infectious-Remove-Susceptible (SEIRS) Model, and adapted the agent-based model (ABM) to construct the epidemic prevention and control model framework to simulate the COVID-19 epidemic from three aspects: social distance, personal protection, and bed resources. The experiment results show that the above NDI are effective mitigation measures for epidemic prevention and control, and can play a positive role in the recurrence of COVID-19, but a single measure cannot prevent the recurrence of infection peaks and curb the spread of the epidemic;When social distance and personal protection rules are out of control, bed resources will become an important guarantee for epidemic prevention and control. Although the spread of the epidemic cannot be curbed, it can slow down the recurrence of the peak of the epidemic;When people abide by social distance and personal protection rules, the pressure on bed resources will be eased. At the same time, under the interaction of the three measures, not only the death toll can be reduced, but the spread of the epidemic can also be effectively curbed. © 2022 ACM.
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According to market research, the pharmaceutical packaging sector is expected to grow at a compound annual rate of 7.4% between 2022 and 2031, reaching an estimated USS178.8 billion (€171.8 billion) by the end of the forecast period (1). "Pharmaceutical waste continues to be a huge problem, so to eliminate non-biodegradable and single-use plastics from the supply chain, more research is taking place around bio-based PET [polyethylene terephthalate]. "By designing a product's primary and secondary packaging well from the outset (including investing ample resources into the process), manufacturers can reduce the amount of materials used and wasted, test new eco materials, ensure safety compliance and efficacy, and benefit from cheaper transportation costs," Quelch surmises. [...]pharma companies can benefit from a packaging supplier with a true global footprint," he says.
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A major driver for innovation within the bio/pharma sector has been the COVID-19 pandemic, which propelled advances such as the approval of messenger RNA (mRNA) vaccines at record-breaking speeds and led to many companies pivoting to deal with the urgent requirements for capacity and supply chain flexibility needed to overcome pandemic challenges. "Before deciding on a location, we conducted extensive market research, and it quickly became clear, just by the sheer proximity of so many biopharmaceutical companies, associations, and research centres, that the event had to be in Geneva. Organized as four half-days, they will each address a theme related to the four main areas of the supply chain present in the exhibition area: pharmaceutical packaging (primary and secondary), medical devices, pharmaceutical sub-contracting, and pharmaceutical equipment. The dream scenario, the real measure of success, is when a product comes to market that happened as a result of a meeting or discussion that took place at our event.
ABSTRACT
Messenger RNAmRNAmedicine was urgently approved in 2020 as a vaccine for COVID-19 . However, current mRNA therapeutics are not fully established, with challenges remaining in translation efficiency and drug delivery system. Therefore, further research is needed to adapt mRNA therapeutics to other diseases. Furthermore, the preparation of mRNA drugs is time-consuming and costly because of the biological methods used. Our laboratory has been working on chemical methods to solve these issues. In this paper, we introduce chemical modifications and novel capping reactions as a method to improve the translation efficiency of mRNA and the introduction of disulfide modification to oligonucleotide therapeutics as an effort on the drug delivery system.Copyright © 2023, Japan Society of Drug Delivery System. All rights reserved.
ABSTRACT
CBD, an FDA approved drug for epilepsy, may have therapeutic potential for other diseases and is currently being tested for efficacy in cancer-related clinical trials. As the literature about CBD, especially in vitro reports, is often contradictory, increasing our understanding of its specific action on a molecular level will allow to determine whether CBD can become a useful therapy or exacerbates specific cancers in a context-dependent manner. Due to its relative lipophilicity, CBD is challenging to dispense at therapeutic concentrations;therefore, one goal is to identify cannabinoid congeners with greater efficacy and reduced drug delivery challenges. We recently showed that CBD activates interferons as a mechanism of inhibiting SARS-CoV-2 replication in lung carcinoma cells. As factors produced by the innate immune system, interferons have been implicated in both pro-survival and growth arrest and apoptosis signaling in cancer. Here we show that CBD induces interferon production and interferon stimulated genes (ISGs) through a mechanism involving NRF2 and MAVS in lung carcinoma cells. We also show that CBDV, which differs from CBD by 2 fewer aliphatic tail carbons, has limited potency, suggesting that CBD specifically interacts with one or more cellular proteins rather than having a non-specific effect. We also identified other CBD-related cannabinoids that are more effective at inducing ISGs. Taken together, these results characterize a novel mechanism by which CBD activates the innate immune system in lung cancer cells and identify related cannabinoids that have possible therapeutic potential in cancer treatment.
ABSTRACT
The issues of practicality in using perfluorocarbon gas transport emulsions (or pure perfluorocarbons) in severe virus-associated pneumonia treatment were considered, including those caused by coronavirus infection. Perfluorocarbons are fully fluorinated carbon compounds, on the basis of which artificial blood substitutes have been developed — gas transport perfluorocarbon emulsions for medical purposes. Perfluorocarbon emulsions were widely used in the treatment of patients in critical conditions of various genesis at the end of the last–the beginning of this century, accompanied by hypoxia, disorders of rheological properties and microcirculation of blood, perfusion of organs and tissues, intoxication, and inflammation. Large-scale clinical trials have shown a domestic plasma substitute advantage based on perfluorocarbons (perfluoroan) over foreign analogues. It is quite obvious that the inclusion of perfluorocarbon emulsions in the treatment regimens of severe virus-associated pneumonia can significantly improve this category's treatment results after analyzing the accumulated experience. A potentially useful area of therapy for acute respiratory distress syndrome is partial fluid ventilation with the use of perfluorocarbons as respiratory fluids as shown in the result of many studies on animal models and existing clinical experience. There is no gas-liquid boundary in the alveoli, as a result of which, there is an improvement in gas exchange in the lungs and a decrease in pressure in the respiratory tract when using this technique, due to the unique physicochemical properties of liquid perfluorocarbons. A promising strategy for improving liquid ventilation effectiveness using perfluorocarbon compounds is a combination with other therapeutic methods, particularly with moderate hypothermia. Antibiotics, anesthetics, vasoactive substances, or exogenous surfactant can be delivered to the lungs during liquid ventilation with perfluorocarbons, including to the affected areas, which will enhance the drugs accumulation in the lung tissues and minimize their systemic effects. However, the indications and the optimal technique for conducting liquid ventilation of the lungs in patients with acute respiratory distress syndrome have not been determined currently. Further research is needed to clarify the indications, select devices, and determine the optimal dosage regimens for perfluorocarbons, as well as search for new technical solutions for this technique The article can be used under the CC BY-NC-ND 4.0 license © Authors, 2022.
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Recent advancements in nanotechnology have resulted in improved medicine delivery to the target site. Nanosponges are three-dimensional drug delivery systems that are nanoscale in size and created by cross-linking polymers. The introduction of Nanosponges has been a significant step toward overcoming issues such as drug toxicity, low bioavailability, and predictable medication release. Using a new way of nanotechnology, nanosponges, which are porous with small sponges (below one microm) flowing throughout the body, have demonstrated excellent results in delivering drugs. As a result, they reach the target place, attach to the skin's surface, and slowly release the medicine. Nanosponges can be used to encapsulate a wide range of medicines, including both hydrophilic and lipophilic pharmaceuticals. The medication delivery method using nanosponges is one of the most promising fields in pharmacy. It can be used as a biocatalyst carrier for vaccines, antibodies, enzymes, and proteins to be released. The existing study enlightens on the preparation method, evaluation, and prospective application in a medication delivery system and also focuses on patents filed in the field of nanosponges.Copyright © 2023 The Authors.
ABSTRACT
Nanofibers are a type of nanomaterial with a diameter ranging from ten to a few hundred nanometers with a high surface-to-volume ratio and porosity. They can build a network of high-porosity material with excellent connectivity within the pores, making them a preferred option for numerous applications. This review explores nanofibers from the synthesis techniques to fabricate nanofibers, with an emphasis on the technological applications of nanofibers like water and air filtration, photovoltaics, batteries and fuel cells, gas sensing, photocatalysis, and biomedical applications like wound dressing and drug delivery. The nanofiber production market has an expected compound annual growth rate (CAGR) of 6% and should reach around 26 million US $ in 2026. The limitations and potential opportunities for large-scale applications of nano-fibrous membranes are also discussed. We expect this review could provide enriched information to better understand Electrospun Polymer Nanofiber Technology and recent advances in this field. © 2023 Bentham Science Publishers.
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Introduction: There is a distinct unmet need in structured, curriculum based, unbiased education in neuromodulation. Current teaching is through sporadic industry workshops, cadaver courses and peer proctorship. The COVID pandemic has created a unique opportunity where online platforms have enabled education to be delivered remotely in both synchronous and asynchronously. The William Harvey Research Institute, Queen Mary University, London, UK have initiated University based accreditation- Post Graduate Certificate in neuromodulation (PGCert) that provides candidate a qualification in one academic year through part-time study. Method(s): The program underwent rigorous staged university approval process (figure 1). To ensure market feasibility, two short proof of concept CPD programs "Executive Education in Neuromodulation (EEPIN)" were delivered in 2021. These courses attracted 87 candidates across Australia, Singapore, India, Germany, Poland, Czech Republic, Ireland, and UK. The faculty includes key opinion leaders that will deliver the program ensuring the candidates gain academic background and specialist skills to understand safe practice of neuromodulation. The PGCert advisory board has been established to ensure strict governance in terms of content and unbiased delivery confirming ACCME guidance. In order to obtain PGCert, candidates are required to complete 4 x 15 credit modules (60 credits). The four modules include Anatomy & Neurophysiology;Patient care and Procedurals skills;Devices and available technology;Intrathecal drug delivery for cancer and non-cancer pain. The modular nature of the program is designed to provide cumulative knowledge, from basic science to clinical application in line with the best available evidence. The modules comprise nine lectures, spreading over three consecutive days, followed by a written assignment with 40 direct contact hours in each module. The webpage can be accessed at Results: The anonymous data from EEPIN reported on Likert scale 1-5: Objectives defined 30.6% - 4 and 69.4% -5;Relevance of topics 10.2%- 4 and 89.8% -5;Content of presentations 22.4%- 4 and 77.6% -5;Organization 24.5% -4 and 69.4% -5;Candidate faculty interaction 14.3% -4 and 81.6% -5. 97% of the EEPIN candidates recommended the program to others whilst 81.8% expressed their strong interest to enroll for university-based post graduate qualification if offered. Conclusion(s): This PGcert Neuromodulation is a unique, university accredited program that provides qualification in neuromodulation with access to a flexible online e-learning platform to discuss and exchange ideas, share knowledge in candidate's own time. This will support the ongoing need for formal curriculum-based education in neuromodulation. Disclosure: Kavita Poply, PHD: None, Phillippe Rigoard: None, Jan Kallewaard, MD/PhD: None, FRANK J.P.M. HUYGEN, MD PhD: ABBOTT: Speakers Bureau:, Saluda: Consulting Fee:, Boston Scientific: Consulting Fee:, Grunenthal: Speakers Bureau:, Pfizer: Speakers Bureau:, Ashish Gulve, FRCA, FFPMRCA, FFPMCAI, DPMed, FCARCSI, MD, MBBS: None, Ganesan Baranidharan, FRCA: None, Sam ELDABE, MD, FRCA, FFPMRCA: Medtronic: Consulting Fee:, Medtronic: Contracted Research:, Mainstay Medical: Consulting Fee:, Saluda Medical: Consulting Fee:, Boston Scientific: Contracted Research:, Saluda Medical: Contracted Research:, James Fitzgerald, MA,PhD: St Jude Medical: Consultant: Self, Medtronic: Consulting Fee:, UCB: Contracted Research:, Merck: Contracted Research:, Serge Nikolic, MD: None, Stana Bojanic, BSc MBBS FRCS (SN): Abbott: Contracted Research:, Habib Ellamushi: None, Paresh Doshi, MS MCh: None, Preeti Doshi, MBBS, MD, FRCA: None, Babita Ghai, MBBS, MD, DNB: None, Marc Russo, MD: Presidio Medical: Ownership Interest:, Saluda Medical: Ownership Interest:, Boston Scientific: Contracted Research: Self, Mainstay Medical: Contracted Research: Self, Medtronic: Contracted Research: Self, Nevro: Contracted Research: Self, Saluda Medical: Contracted Research: Self, Presidio Medical: Contracted Research: Self, Freedom Ne ro: Ownership Interest - Own Stocks: Self, Lungpacer: Ownership Interest - Own Stocks: Self, SPR Therapeutics: Ownership Interest - Own Stocks: Self, Lawrence Poree, MD,MPH,PHD: Medtronic: Consulting Fee: Self, Saluda Medical: Contracted Research: Family, Nalu Medical: Contracted Research: Family, Gimer Medical: Consulting Fee: Self, Nalu Medical: Consulting Fee: Self, Saluda Medical: Consulting Fee: Self, Nalu: Ownership Interest:, Saluda Inc: Ownership Interest:, Alia Ahmad: None, Alaa Abd Sayed, MD: Medtronic, Abbott, SPR and StimWave: Consulting Fee:, Salim Hayek, MD,PhD: None, CHRISTOPHER GILLIGAN, MD MBA: Persica: Consulting Fee: Self, Saluda: Consulting Fee: Self, Mainstay Medical: Contracted Research: Self, Sollis Therapeutics: Contracted Research: Self, Iliad Lifesciences, LLC: Owner: individuals with legal ownership in a company:, Vivek Mehta: NoneCopyright © 2023
ABSTRACT
Vaccination has been proved to be the most effective strategy to prevent the Corona Virus Disease 2019 (COVID-19). The mRNA vaccine based on nano drug delivery system (NDDS) - lipid nanoparticles (LNP) has been widely used because of its high effectiveness and safety. Although there have been reports of severe allergic reactions caused by mRNA-LNP vaccines, the mechanism and components of anaphylaxis have not been completely clarified yet. This review focuses on two mRNA-LNP vaccines, BNT162b2 and mRNA-1273. After summarizing the structural characteristics, potential allergens, possible allergic reaction mechanism, and pharmacokinetics of mRNA and LNP in vivo, this article then reviews the evaluation methods for patients with allergic history, as well as the regulations of different countries and regions on people who should not be vaccinated, in order to promote more safe injection of vaccines. LNP has become a recognized highly customizable nucleic acid delivery vector, which not only shows its value in mRNA vaccines, but also has great potential in treating rare diseases, cancers and other broad fields in the future. At the moment when mRNA-LNP vaccines open a new era of nano medicine, it is expected to provide some inspiration for safety research in the process of research, development and evaluation of more nano delivery drugs, and promote more nano drugs successfully to market.Copyright © 2023, Chinese Pharmaceutical Association. All rights reserved.
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The heart, liver, lungs, brain and kidney are the five most highly perfused organs. Incidentally, they are the ones prone to many diseases and disorders. There has been a phenomenal rise in lung diseases in the recent past which can be attributed to rising levels of environmental pollution, smoking and other lifestyle problems. The cytokine storm experienced in the COVID-19-affected population was a recent challenge faced by physicians around the globe. Scientists have tried different methods and delivery systems for effective delivery of drugs to the lungs. Pectin-based drug delivery systems have also been tried and tested suc- cessfully. This chapter will focus on the bumps and humps in the use of pectin as an effective polymer in delivering therapeutics to the lungs and management of various respiratory disorders. © The Author (s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.
ABSTRACT
Coronavirus disease (COVID-19) is an infectious disease caused by coronavirus. Devel-oping specific drugs for inhibiting replication and viral entry is crucial. Several clinical trial studies are underway to evaluate the efficacy of anti-viral drugs for COVID-19 patients. Nanomedicine formulations can present a novel strategy for targeting the virus life cycle. Nano-drug delivery systems can modify the pharmacodynamics and pharmacokinetics properties of anti-viral drugs and reduce their adverse effects. Moreover, nanocarriers can directly exhibit anti-viral effects. A number of nanocarriers have been studied for this purpose, including liposomes, dendrimers, exosomes and decoy nanoparticles (NPs). Among them, decoy NPs have been considered more as nanodecoys can efficiently protect host cells from the infection of SARS-CoV-2. The aim of this review article is to highlight the probable nanomedicine therapeutic strategies to develop anti-viral drug delivery systems for the treatment of COVID-19.Copyright © 2023 Bentham Science Publishers.
ABSTRACT
Background & Aim: Liposomes are spherical-shaped vesicles composed of one or more lipid bilayers. The ability of liposomes to encapsulate hydro- or lipophilic drugs allowed these vesicles to become a useful drug delivery system. Natural cell membranes, such as Bioxome, have newly emerged as new source of materials for molecular delivery systems. Bioxome are biocompatible and GMP-compliant liposome-like membrane that can be produced from more than 200 cell types. Bioxome self-assemble, with in-process self-loading capacity and can be loaded with a variety of therapeutic compounds. Once close to the target tissue, Bioxome naturally fuse with the cell membrane and release the inner compound. Orgenesis is interested in evaluating the potential of Bioxome as new drug delivery system for treatment of several diseases, including skin repair, local tumour or COVID19. Methods, Results & Conclusion(s): Bioxome were obtained from adipose- derived Mesenchymal Stem Cells, with a process of organic- solvent lipid extraction, followed by lyophilization and sonication assemblage. During the sonication process, Bioxome were charged or not with several cargos. Size distribution of empty Bioxome was detected by Particle Size Analyzer (NanoSight). Electron Microscopy (EM) was performed to assess Bioxome morphology. Lipid content was evaluated by electrospray ionization system. Dose response in vitro test on human lung fibroblasts treated or not with Bioxome encapsulating a specific cargo (API) against COVID19 were performed. NanoSight analysis showed that nanoparticle size in Bioxome samples ranged between 170+/-50 nm, with a concentration ranging between 109-1010+/-106 particles/mL. EM clearly showed the double phospholipid layers that composes the Bioxome. Stability study demonstrated that Bioxome are stable in size and concentration up to 90 days at +4Cdegree or even at RT. No change in size between encapsulated Bioxome with small size (~340 Da) cargo vs empty Bioxome was observed up to 30 days storage. Lipidomic analysis approach revealed that the yield of lipids and their composition are satisfactory for a therapeutic product using Bioxome. Lastly, in the in vitro model of COVID19, Bioxome encapsulating API effectively saved cells from death (20x vs untreated cells) and at lower doses of API than these of non-encapsulated cargo (0.005 microM vs 0.1 microM). Bioxome seems to be an excellent candidate for liposome mimetic tool as drug delivery system for targeting specific organs and diseases treatment.Copyright © 2023 International Society for Cell & Gene Therapy
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Reducing the molecule complexity is achieved by reducing the molecule size after enzymatic digestion to produce smaller fragments more amenable to LC separation and tandem mass spectrometry (MS/MS) sequencing. Non-denaturing CEX chromatography, size-exclusion chromatogra- phy (SEC), hydrophobic interaction chromatography (HIC), and protein A modes can be easily coupled to reversed-phase LC (RPLC) because of the high aqueous conditions, enabling the versatile 4D-LC-MS systems with the use of alternative modes to 1D CEX, such as SEC or Protein A (6,7). [...]the nanopar-ticle size and free drug concentration are determined at the particle Level, whereas the encapsulated drug and lipids forming the layer are commonly characterized at the molecuar level after denaturing the lipid nanoparticle (LNP) via a surfactant. [...]MDLC-MS setups present a formidable opportunity to unify the characterization of drug delivery systems at the molecular and particle evels, which would enable their high throughput analysis.
ABSTRACT
Pulmonary disorders are common illness that affects people of all ages worldwide. Common pulmonary disorders include pulmonary hypertension, CF (cystic fibrosis), asthma, chronic obstructive pulmonary disorder, emphysema, chronic bronchitis, lung cancer, and COVID-19. Treatments of these disorders vary but can be broadly categorized into pharmacological (medicinal), non-pharmacological, rehabilitation, and surgical techniques. Often, a combination of these approaches is used, both for symptomatic relief and treatment. Regarding these prophylactic and therapeutic approaches, advances are rapidly being made, and scientists are currently investigating modern and unique theranostic methods. However, there is a lacuna in drug delivery, pharmacokinetic aspects, and drug-induced adverse effects. One particular area for improvement that needs to be immediately addressed is the drug delivery system to significantly improve healthcare associated with pulmonary disorders. Natural polymer-based drug delivery systems are widely adopted for their ease of production, lack of biotoxicity, and strong bioaffinity. Of the natural polymerbased drug delivery systems, chitosan, sodium alginates, albumin, hydroxyapatite, and hyaluronic acid are the most common natural polymers. Each of these natural polymers has its preferred use, either due to tissue-specific delivery or medical property packaging. The current scientific article discusses the common pulmonary disorders, their pathophysiology, and the current therapeutic approaches. Additionally, we discuss the major natural polymer drug delivery systems, including their properties and common uses. © The Author (s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.
ABSTRACT
Nucleic acids, as a next generation of biotechnology drugs, not only can fundamentally treat diseases, but also own significant platform characteristics in view of technology and production. Therefore, nucleic acid-based drugs have broad clinical applications in biomedical fields. However, nucleic acids are degradable and unstable, and have very low intracellular delivery efficiency in vitro and in vivo, which greatly limits their applications. In recent years, ionizable lipid-based lipid nanoparticles have shown promising application potentials and have been successfully applied to COVID-19 (Coronavirus Disease 2019) vaccines in clinic. Lipid nanoparticles demonstrate high in vivo delivery efficiency and good safety profile due to their unique structural and physicochemical properties, which provides many possibilities for their clinical applications for nucleic acid delivery in the future. This review focused on the characteristics of nucleic acid drugs and their delivery barriers, and discussed the approved nucleic acid drugs to illustrate the key aspects of the success of their delivery carrier system. In addition, problems to be solved in the field were highlighted.Copyright © 2023, Chinese Pharmaceutical Association. All rights reserved.
ABSTRACT
In 2020, COVID-19 changed how health care was approached both in the United States and globally. In the early phases, the vast majority of energy and attention was devoted to containing the pandemic and treating the infected. Toward the end of 2020, that attention expanded to vaccinating people across the globe. What was not being considered at the time were challenges to future health and clinical trials that power new treatments for COVID-19 and non-COVID-19 treatments. © 2023 Elsevier Inc. All rights reserved.
ABSTRACT
Ivermectin is an antiparasitic drug that results in the death of the targeted parasites using several mechanical actions. While very well supported, it can induce in rare cases, adverse effects including coma and respiratory failure in case of overdose. This problem should be solved especially in an emergency situation. For instance, the first pandemic of the 21th century was officially declared in early 2020, and while several vaccines around the worlds have been used, an effective treatment against this new strain of coronavirus, better known as SARS-CoV-2, should also be considered, especially given the massive appearance of variants. From all the tested therapies, Ivermectin showed a potential reduction of the viral portability, but sparked significant debate around the dose needed to achieve these positive results. To answer this general question, we propose, using simulations, to show that the nanovectorization of Ivermectin on BN oxide nanosheets can increase the transfer of the drug to its target and thus decrease the quantity of drug necessary to cope with the disease. This first application could help science to develop such nanocargo to avoid adverse effects.Communicated by Ramaswamy H. Sarma.
ABSTRACT
Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) induces a severe cytokine storm that may cause acute lung injury/acute respiratory distress syndrome (ALI/ARDS) with high clinical morbidity and mortality in infected individuals. Cepharanthine (CEP) is a bisbenzylisoquinoline alkaloid isolated and extracted from Stephania cepharantha Hayata. It exhibits various pharmacological effects, including antioxidant, anti-inflammatory, immunomodulatory, anti-tumor, and antiviral activities. The low oral bioavailability of CEP can be attributed to its poor water solubility. In this study, we utilized the freeze-drying method to prepare dry powder inhalers (DPI) for the treatment of acute lung injury (ALI) in rats via pulmonary administration. According to the powder properties study, the aerodynamic median diameter (Da) of the DPIs was 3.2 µm, and the in vitro lung deposition rate was 30.26; thus, meeting the Chinese Pharmacopoeia standard for pulmonary inhalation administration. We established an ALI rat model by intratracheal injection of hydrochloric acid (1.2 mL/kg, pH = 1.25). At 1 h after the model's establishment, CEP dry powder inhalers (CEP DPIs) (30 mg/kg) were sprayed into the lungs of rats with ALI via the trachea. Compared with the model group, the treatment group exhibited a reduced pulmonary edema and hemorrhage, and significantly reduced content of inflammatory factors (TNF-α, IL-6 and total protein) in their lungs (p < 0.01), indicating that the main mechanism of CEP underlying the treatment of ALI is anti-inflammation. Overall, the dry powder inhaler can deliver the drug directly to the site of the disease, increasing the intrapulmonary utilization of CEP and improving its efficacy, making it a promising inhalable formulation for the treatment of ALI.
Subject(s)
Acute Lung Injury , Benzylisoquinolines , COVID-19 , Rats , Animals , Administration, Inhalation , Dry Powder Inhalers , COVID-19/metabolism , SARS-CoV-2 , Respiratory Aerosols and Droplets , Lung/metabolism , Acute Lung Injury/drug therapy , Acute Lung Injury/metabolism , Benzylisoquinolines/pharmacology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/analysis , Particle Size , Powders/analysisABSTRACT
Easily deploying new vaccines globally to combat disease outbreaks has been highlighted as a major necessity by the World Health Organization. RNA-based vaccines using lipid nanoparticles (LNPs) as a drug delivery system were employed to great effect during the recent COVID-19 pandemic. However, LNPs are still unstable at room temperature and agglomerate over time during storage, rendering them ineffective for intracellular delivery. We demonstrate the suitability of nanohole arrays (nanopackaging) as patterned surfaces to separate and store functionalized LNPs (fLNPs) in individual recesses, which can be expanded to other therapeutics. Encapsulating calcein as a model drug, we show through confocal microscopy the effective loading of fLNPs into our nanopackaging for both wet and dry systems. We prove quantifiably pH-mediated capture and subsequent unloading of over 30% of the fLNPs using QCM-D on alumina surfaces altering the pH from 5.5 to 7, displaying controllable storage at the nanoscale.