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1.
Drug Deliv ; 29(1): 386-398, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2187330

ABSTRACT

The potential of nucleic acid therapeutics to treat diseases by targeting specific cells has resulted in its increasing number of uses in clinical settings. However, the major challenge is to deliver bio-macromolecules into target cells and/or subcellular locations of interest ahead in the development of delivery systems. Although, supercharged residues replaced protein 36 + GFP can facilitate itself and cargoes delivery, its efficiency is still limited. Therefore, we combined our recent progress to further improve 36 + GFP based delivery efficiency. We found that the penetration efficacy of 36 + GFP protein was significantly improved by fusion with CPP-Dot1l or treatment with penetration enhancer dimethyl sulfoxide (DMSO) in vitro. After safely packaged with plasmid DNA, we found that the efficacy of in vitro and in vivo transfection mediated by 36 + GFP-Dot1l fusion protein is also significantly improved than 36 + GFP itself. Our findings illustrated that fusion with CPP-Dot1l or incubation with DMSO is an alternative way to synergically promote 36 + GFP mediated plasmid DNA delivery in vitro and in vivo.


Subject(s)
Cell-Penetrating Peptides/pharmacokinetics , Drug Delivery Systems/methods , Green Fluorescent Proteins/pharmacokinetics , Histone-Lysine N-Methyltransferase/pharmacokinetics , Nucleic Acids/administration & dosage , Animals , Cell Line, Tumor , Cell Survival/drug effects , Dimethyl Sulfoxide/chemistry , Green Fluorescent Proteins/chemistry , Hemolysis/drug effects , Humans , Mice , Particle Size , Surface Properties , Transfection/methods
2.
Brief Bioinform ; 23(6)2022 Nov 19.
Article in English | MEDLINE | ID: covidwho-2134850

ABSTRACT

Exiting computational models for drug-target binding affinity prediction have much room for improvement in prediction accuracy, robustness and generalization ability. Most deep learning models lack interpretability analysis and few studies provide application examples. Based on these observations, we presented a novel model named Molecule Representation Block-based Drug-Target binding Affinity prediction (MRBDTA). MRBDTA is composed of embedding and positional encoding, molecule representation block and interaction learning module. The advantages of MRBDTA are reflected in three aspects: (i) developing Trans block to extract molecule features through improving the encoder of transformer, (ii) introducing skip connection at encoder level in Trans block and (iii) enhancing the ability to capture interaction sites between proteins and drugs. The test results on two benchmark datasets manifest that MRBDTA achieves the best performance compared with 11 state-of-the-art models. Besides, through replacing Trans block with single Trans encoder and removing skip connection in Trans block, we verified that Trans block and skip connection could effectively improve the prediction accuracy and reliability of MRBDTA. Then, relying on multi-head attention mechanism, we performed interpretability analysis to illustrate that MRBDTA can correctly capture part of interaction sites between proteins and drugs. In case studies, we firstly employed MRBDTA to predict binding affinities between Food and Drug Administration-approved drugs and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication-related proteins. Secondly, we compared true binding affinities between 3C-like proteinase and 185 drugs with those predicted by MRBDTA. The final results of case studies reveal reliable performance of MRBDTA in drug design for SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , United States , Humans , Reproducibility of Results , Drug Delivery Systems , Proteins
3.
Curr Med Chem ; 29(3): 526-590, 2022.
Article in English | MEDLINE | ID: covidwho-2141212

ABSTRACT

Pulmonary surfactant is a complex lipoprotein mixture secreted into the alveolar lumen by type 2 pneumocytes, which is composed by tens of different lipids (approximately 90% of its entire mass) and surfactant proteins (approximately 10% of the mass). It is crucially involved in maintaining lung homeostasis by reducing the values of alveolar liquid surface tension close to zero at end-expiration, thereby avoiding the alveolar collapse, and assembling a chemical and physical barrier against inhaled pathogens. A deficient amount of surfactant or its functional inactivation is directly linked to a wide range of lung pathologies, including the neonatal respiratory distress syndrome. This paper reviews the main biophysical concepts of surfactant activity and its inactivation mechanisms, and describes the past, present and future roles of surfactant replacement therapy, focusing on the exogenous surfactant preparations marketed worldwide and new formulations under development. The closing section describes the pulmonary surfactant in the context of drug delivery. Thanks to its peculiar composition, biocompatibility, and alveolar spreading capability, the surfactant may work not only as a shuttle to the branched anatomy of the lung for other drugs but also as a modulator for their release, leading to innovative therapeutic avenues for the treatment of several respiratory diseases.


Subject(s)
Pulmonary Surfactants , Respiratory Distress Syndrome, Newborn , Biocompatible Materials/therapeutic use , Drug Delivery Systems , Humans , Infant, Newborn , Lung , Pulmonary Surfactants/therapeutic use , Respiratory Distress Syndrome, Newborn/drug therapy
4.
Adv Drug Deliv Rev ; 186: 114325, 2022 07.
Article in English | MEDLINE | ID: covidwho-2114698

ABSTRACT

With the pandemic of severe acute respiratory syndrome coronavirus 2, vaccine delivery systems emerged as a core technology for global public health. Given that antigen processing takes place inside the cell, the intracellular delivery and trafficking of a vaccine antigen will contribute to vaccine efficiency. Investigations focusing on the in vivo behavior and intracellular transport of vaccines have improved our understanding of the mechanisms relevant to vaccine delivery systems and facilitated the design of novel potent vaccine platforms. In this review, we cover the intracellular trafficking and in vivo fate of vaccines administered via various routes and delivery systems. To improve immune responses, researchers have used various strategies to modulate vaccine platforms and intracellular trafficking. In addition to progress in vaccine trafficking studies, the challenges and future perspectives for designing next-generation vaccines are discussed.


Subject(s)
COVID-19 , Vaccines , Antigens , COVID-19/prevention & control , Drug Delivery Systems , Humans
6.
J Nanobiotechnology ; 20(1): 395, 2022 Aug 31.
Article in English | MEDLINE | ID: covidwho-2038770

ABSTRACT

The rapid advancement of nanomedicine and nanoparticle (NP) materials presents novel solutions potentially capable of revolutionizing health care by improving efficacy, bioavailability, drug targeting, and safety. NPs are intriguing when considering medical applications because of their essential and unique qualities, including a significantly higher surface to mass ratio, quantum properties, and the potential to adsorb and transport drugs and other compounds. However, NPs must overcome or navigate several biological barriers of the human body to successfully deliver drugs at precise locations. Engineering the drug carrier biointerface can help overcome the main biological barriers and optimize the drug delivery in a more personalized manner. This review discusses the significant heterogeneous biological delivery barriers and how biointerface engineering can promote drug carriers to prevail over hurdles and navigate in a more personalized manner, thus ushering in the era of Precision Medicine. We also summarize the nanomedicines' current advantages and disadvantages in drug administration, from natural/synthetic sources to clinical applications. Additionally, we explore the innovative NP designs used in both non-personalized and customized applications as well as how they can attain a precise therapeutic strategy.


Subject(s)
Drug Delivery Systems , Nanoparticles , Drug Carriers , Humans , Nanomedicine , Nanoparticles/therapeutic use , Precision Medicine
7.
Molecules ; 27(16)2022 Aug 22.
Article in English | MEDLINE | ID: covidwho-2023940

ABSTRACT

Tuberculosis (TB) caused by the bacterial pathogen Mycobacterium tuberculosis (Mtb) remains a threat to mankind, with over a billion of deaths in the last two centuries. Recent advancements in science have contributed to an understanding of Mtb pathogenesis and developed effective control tools, including effective drugs to control the global pandemic. However, the emergence of drug resistant Mtb strains has seriously affected the TB eradication program around the world. There is, therefore, an urgent need to develop new drugs for TB treatment, which has grown researchers' interest in small molecule-based drug designing and development. The small molecules-based treatments hold significant potential to overcome drug resistance and even provide opportunities for multimodal therapy. In this context, various natural and synthetic flavonoids were reported for the effective treatment of TB. In this review, we have summarized the recent advancement in the understanding of Mtb pathogenesis and the importance of both natural and synthetic flavonoids against Mtb infection studied using in vitro and in silico methods. We have also included flavonoids that are able to inhibit the growth of non-tubercular mycobacterial organisms. Hence, understanding the therapeutic properties of flavonoids can be useful for the future treatment of TB.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Drug Delivery Systems , Flavonoids/pharmacology , Flavonoids/therapeutic use , Humans , Tuberculosis/drug therapy , Tuberculosis/microbiology
8.
Mar Drugs ; 20(8)2022 Aug 18.
Article in English | MEDLINE | ID: covidwho-2023893

ABSTRACT

The increased interest in nanomedicine and its applicability for a wide range of biological functions demands the search for raw materials to create nanomaterials. Recent trends have focused on the use of green chemistry to synthesize metal and metal-oxide nanoparticles. Bioactive chemicals have been found in a variety of marine organisms, including invertebrates, marine mammals, fish, algae, plankton, fungi, and bacteria. These marine-derived active chemicals have been widely used for various biological properties. Marine-derived materials, either whole extracts or pure components, are employed in the synthesis of nanoparticles due to their ease of availability, low cost of production, biocompatibility, and low cytotoxicity toward eukaryotic cells. These marine-derived nanomaterials have been employed to treat infectious diseases caused by bacteria, fungi, and viruses as well as treat non-infectious diseases, such as tumors, cancer, inflammatory responses, and diabetes, and support wound healing. Furthermore, several polymeric materials derived from the marine, such as chitosan and alginate, are exploited as nanocarriers in drug delivery. Moreover, a variety of pure bioactive compounds have been loaded onto polymeric nanocarriers and employed to treat infectious and non-infectious diseases. The current review is focused on a thorough overview of nanoparticle synthesis and its biological applications made from their entire extracts or pure chemicals derived from marine sources.


Subject(s)
Chitosan , Metal Nanoparticles , Nanoparticles , Neoplasms , Noncommunicable Diseases , Animals , Bacteria , Chitosan/chemistry , Drug Delivery Systems , Fungi , Mammals , Metal Nanoparticles/chemistry , Nanoparticles/chemistry , Neoplasms/drug therapy , Noncommunicable Diseases/drug therapy , Pharmaceutical Preparations , Polymers/therapeutic use
9.
Adv Healthc Mater ; 11(7): e2101349, 2022 04.
Article in English | MEDLINE | ID: covidwho-1381824

ABSTRACT

White blood cells (WBCs) are immune cells that play essential roles in critical diseases including cancers, infections, and inflammatory disorders. Their dynamic and diverse functions have inspired the development of WBC membrane-coated nanoparticles (denoted "WBC-NPs"), which are formed by fusing the plasma membranes of WBCs, such as macrophages, neutrophils, T cells, and natural killer cells, onto synthetic nanoparticle cores. Inheriting the entire source cell antigens, WBC-NPs act as source cell decoys and simulate their broad biointerfacing properties with intriguing therapeutic potentials. Herein, the recent development and medical applications of WBC-NPs focusing on four areas, including WBC-NPs as carriers for drug delivery, as countermeasures for biological neutralization, as nanovaccines for immune modulation, and as tools for the isolation of circulating tumor cells and fundamental research is reviewed. Overall, the recent development and studies of WBC-NPs have established the platform as versatile nanotherapeutics and tools with broad medical application potentials.


Subject(s)
Nanoparticles , Neoplasms , Cell Membrane/metabolism , Drug Delivery Systems , Humans , Leukocytes , Neoplasms/drug therapy , Neoplasms/metabolism
10.
J Mater Chem B ; 10(30): 5666-5695, 2022 08 04.
Article in English | MEDLINE | ID: covidwho-1947652

ABSTRACT

Lung diseases remain a global burden today. Lower respiratory tract infections alone cause more than 3 million deaths worldwide each year and are on the rise every year. In particular, with coronavirus disease raging worldwide since 2019, we urgently require a treatment for lung disease. Metal organic frameworks (MOFs) have a broad application prospect in the biomedical field due to their remarkable properties. The unique properties of MOFs allow them to be applied as delivery materials for different drugs; diversified structural design endows MOFs with diverse functions; and they can be designed as various MOF-drug synergistic systems. This review concentrates on the synthesis design and applications of MOF based drugs against lung diseases, and discusses the possibility of preparing MOF-based inhalable formulations. Finally, we discuss the chances and challenges of using MOFs for targeting lung diseases in clinical practice.


Subject(s)
Lung Diseases , Metal-Organic Frameworks , Drug Delivery Systems , Humans , Lung Diseases/drug therapy , Metal-Organic Frameworks/pharmacology , Metal-Organic Frameworks/therapeutic use
11.
Drug Deliv ; 28(1): 856-864, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1947906

ABSTRACT

SARS-CoV-2 is a novel coronavirus that was isolated and identified for the first time in Wuhan, China in 2019. Nowadays, it is a worldwide danger and the WHO named it a pandemic. In this investigation, a functionalization post-synthesis method was used to assess the ability of an adapted SBA-15 surface as a sorbent to load the drug from an aqueous medium. Different characterization approaches were used to determine the characterization of the substance before and after functionalization such as X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), nitrogen adsorption-desorption porosimetry (Brunauer-Emmett-Teller) BET surface area analysis, and thermal gravimetric analysis (TGA). Batch adsorption testing was carried out in a single adsorption device to find the impact of multiple variables on the drug amoxicillin charge output. The following parameters were studied: 0-72 hr. contact time, 20-120 mg/l initial concentration, and 20-250 mg of NH2-SBA-15 dose. The outcomes from such experiments revealed the strong influence and behavior of the amino-functional group to increase the drug's load. Drug delivery outcomes studies found that amoxicillin loading was directly related to NH2-SBA-15 contact time and dose, but indirectly related to primary concentration. It was observed that 80% of amoxicillin was loaded while the best release test results were 1 hour and 51%.


Subject(s)
Amoxicillin/therapeutic use , COVID-19/drug therapy , Silicon Dioxide/chemistry , Amoxicillin/administration & dosage , Chemistry, Pharmaceutical , Dose-Response Relationship, Drug , Drug Delivery Systems , Humans , Microscopy, Electron, Scanning , Porosity , SARS-CoV-2 , Spectroscopy, Fourier Transform Infrared , Surface Properties , X-Ray Diffraction
12.
Int J Mol Sci ; 22(18)2021 Sep 19.
Article in English | MEDLINE | ID: covidwho-1934141

ABSTRACT

Central nervous system (CNS) diseases are the leading causes of death and disabilities in the world. It is quite challenging to treat CNS diseases efficiently because of the blood-brain barrier (BBB). It is a physical barrier with tight junction proteins and high selectivity to limit the substance transportation between the blood and neural tissues. Thus, it is important to understand BBB transport mechanisms for developing novel drug carriers to overcome the BBB. This paper introduces the structure of the BBB and its physiological transport mechanisms. Meanwhile, different strategies for crossing the BBB by using nanomaterial-based drug carriers are reviewed, including carrier-mediated, adsorptive-mediated, and receptor-mediated transcytosis. Since the viral-induced CNS diseases are associated with BBB breakdown, various neurotropic viruses and their mechanisms on BBB disruption are reviewed and discussed, which are considered as an alternative solution to overcome the BBB. Therefore, most recent studies on virus-mimicking nanocarriers for drug delivery to cross the BBB are also reviewed and discussed. On the other hand, the routes of administration of drug-loaded nanocarriers to the CNS have been reviewed. In sum, this paper reviews and discusses various strategies and routes of nano-formulated drug delivery systems across the BBB to the brain, which will contribute to the advanced diagnosis and treatment of CNS diseases.


Subject(s)
Blood-Brain Barrier/metabolism , Drug Carriers/chemistry , Drug Delivery Systems , Nanostructures/chemistry , Animals , Biological Transport , Humans
13.
CNS Drugs ; 36(7): 739-770, 2022 07.
Article in English | MEDLINE | ID: covidwho-1930607

ABSTRACT

While the intranasal administration of drugs to the brain has been gaining both research attention and regulatory success over the past several years, key fundamental and translational challenges remain to fully leveraging the promise of this drug delivery pathway for improving the treatment of various neurological and psychiatric illnesses. In response, this review highlights the current state of understanding of the nose-to-brain drug delivery pathway and how both biological and clinical barriers to drug transport using the pathway can been addressed, as illustrated by demonstrations of how currently approved intranasal sprays leverage these pathways to enable the design of successful therapies. Moving forward, aiming to better exploit the understanding of this fundamental pathway, we also outline the development of nanoparticle systems that show improvement in delivering approved drugs to the brain and how engineered nanoparticle formulations could aid in breakthroughs in terms of delivering emerging drugs and therapeutics while avoiding systemic adverse effects.


Subject(s)
Mental Disorders , Administration, Intranasal , Brain/metabolism , Drug Delivery Systems , Humans , Mental Disorders/drug therapy , Mental Disorders/metabolism , Nose , Pharmaceutical Preparations/metabolism
14.
Biomolecules ; 12(7)2022 07 03.
Article in English | MEDLINE | ID: covidwho-1928472

ABSTRACT

In recent years, the study of metal complexes and metal-based nanomaterials has aroused particular interest, leading to the promotion of new effective systems for the abatement of various viral diseases. Starting from the analysis of chemical properties, this review focuses on the employment of metal-based nanoparticles as antiviral drugs and how this interaction leads to a substantial enhancement in antiviral activity. The use of metal-based antiviral drugs has also spread for the formulation of antiviral vaccines, thanks especially to the remarkable adjuvant activities of some of the metal complexes. In particular, the small size and inert nature of Au- and Ag-based nanoparticles have been exploited for the design of systems for antiviral drug delivery, leading to the development of specific and safe therapies that lead to a decrease in side effects.


Subject(s)
Coordination Complexes , Metal Nanoparticles , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Coordination Complexes/therapeutic use , Drug Delivery Systems , Metal Nanoparticles/chemistry , Metal Nanoparticles/therapeutic use , Pharmaceutical Preparations
15.
Pharmacol Rev ; 74(3): 462-505, 2022 07.
Article in English | MEDLINE | ID: covidwho-1901904

ABSTRACT

The concept of local formation of angiotensin II in the kidney has changed over the last 10-15 years. Local synthesis of angiotensinogen in the proximal tubule has been proposed, combined with prorenin synthesis in the collecting duct. Binding of prorenin via the so-called (pro)renin receptor has been introduced, as well as megalin-mediated uptake of filtered plasma-derived renin-angiotensin system (RAS) components. Moreover, angiotensin metabolites other than angiotensin II [notably angiotensin-(1-7)] exist, and angiotensins exert their effects via three different receptors, of which angiotensin II type 2 and Mas receptors are considered renoprotective, possibly in a sex-specific manner, whereas angiotensin II type 1 (AT1) receptors are believed to be deleterious. Additionally, internalized angiotensin II may stimulate intracellular receptors. Angiotensin-converting enzyme 2 (ACE2) not only generates angiotensin-(1-7) but also acts as coronavirus receptor. Multiple, if not all, cardiovascular diseases involve the kidney RAS, with renal AT1 receptors often being claimed to exert a crucial role. Urinary RAS component levels, depending on filtration, reabsorption, and local release, are believed to reflect renal RAS activity. Finally, both existing drugs (RAS inhibitors, cyclooxygenase inhibitors) and novel drugs (angiotensin receptor/neprilysin inhibitors, sodium-glucose cotransporter-2 inhibitors, soluble ACE2) affect renal angiotensin formation, thereby displaying cardiovascular efficacy. Particular in the case of the latter three, an important question is to what degree they induce renoprotection (e.g., in a renal RAS-dependent manner). This review provides a unifying view, explaining not only how kidney angiotensin formation occurs and how it is affected by drugs but also why drugs are renoprotective when altering the renal RAS. SIGNIFICANCE STATEMENT: Angiotensin formation in the kidney is widely accepted but little understood, and multiple, often contrasting concepts have been put forward over the last two decades. This paper offers a unifying view, simultaneously explaining how existing and novel drugs exert renoprotection by interfering with kidney angiotensin formation.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Sodium-Glucose Transporter 2 Inhibitors , Angiotensin II/metabolism , Angiotensin-Converting Enzyme 2 , Angiotensinogen/metabolism , Cardiovascular Diseases/metabolism , Diabetes Mellitus, Type 2/metabolism , Drug Delivery Systems , Female , Humans , Kidney/blood supply , Kidney/metabolism , Male , Renin/metabolism , Renin-Angiotensin System , Sodium-Glucose Transporter 2 Inhibitors/metabolism
16.
ACS Appl Bio Mater ; 5(7): 3371-3383, 2022 07 18.
Article in English | MEDLINE | ID: covidwho-1900419

ABSTRACT

COVID-19 has resulted in more than 490 million people being infected worldwide, with over 6 million deaths by April 05th, 2022. Even though the development of safe vaccine options is an important step to reduce viral transmission and disease progression, COVID-19 cases will continue to occur, and for those cases, efficient treatment remains to be developed. Here, a drug repurposing strategy using nanotechnology is explored to develop a therapy for COVID-19 treatment. Nanoparticles (NPs) based on PLGA for fingolimod (FTY720) encapsulation show a size of ∼150 nm and high drug entrapment (∼90%). The NP (NP@FTY720) can control FTY720 release in a pH-dependent manner. Cytotoxicity assays using different cell lines show that NP@FTY720 displays less toxicity than the free drug. Flow cytometry and confocal microscopy reveal that NPs are actively internalized mostly through caveolin-mediated endocytosis and macropinocytosis pathways and co-localized with lysosomes. Finally, NP@FTY720 not only exhibits anti-SARS-CoV-2 activity at non-cytotoxic concentrations, but its biological potential for viral infection inhibition is nearly 70 times higher than that of free drug treatment. Based on these findings, the combination of drug repurposing and nanotechnology as NP@FTY720 is presented for the first time and represents a promising frontline in the fight against COVID-19.


Subject(s)
COVID-19 , Fingolimod Hydrochloride , COVID-19/drug therapy , Drug Delivery Systems/methods , Fingolimod Hydrochloride/pharmacology , Humans , SARS-CoV-2
17.
J Drug Target ; 30(2): 151-165, 2022 02.
Article in English | MEDLINE | ID: covidwho-1895637

ABSTRACT

Nanoscale engineering is one of the novel methods to cure multitudes of diseases, such as types of cancers, neurological disorders, and infectious illnesses. Viruses can play a vital role in nanoscale engineering due to their specific properties like minuscule size, high stability in different body conditions, and large-scale production. Viral-like particles (VLPs) as specific nanoscale scaffolds can encapsulate a wide range of cargos, including nucleic acids, proteins, peptides, and drugs. The Exterior portion of VLPs can be changed by genetical or chemical conjugation as well as targeting ligands or peptides. The aforementioned features of VLPs can be used in several applications, such as drug delivery, bioimaging, tissue engineering, vaccine production, and disease detection. This review article attempts to investigate appearance characteristics, modification strategies, and manufacturing methods of VLPs. Additionally, drug delivery to cancer cells as one of the VLPs applications along with different cellular uptake mechanisms of VLPs by cancer cells are chosen for investigation. This review also tries to gather most of the recent studies of drug delivery to cancer cells by VLPs.


Subject(s)
Nanoparticles , Neoplasms , Viruses , Drug Delivery Systems , Humans , Neoplasms/drug therapy , Peptides
18.
ACS Biomater Sci Eng ; 8(7): 2825-2848, 2022 07 11.
Article in English | MEDLINE | ID: covidwho-1890110

ABSTRACT

Mucus layers (McLs) are on the front line of the human defense system that protect us from foreign abiotic/biotic particles (e.g., airborne virus SARS-CoV-2) and lubricates our organs. Recently, the impact of McLs on human health (e.g., nutrient absorption and drug delivery) and diseases (e.g., infections and cancers) has been studied extensively, yet their mechanisms are still not fully understood due to their high variety among organs and individuals. We characterize these variances as the heterogeneity of McLs, which lies in the thickness, composition, and physiology, making the systematic research on the roles of McLs in human health and diseases very challenging. To advance mucosal organoids and develop effective drug delivery systems, a comprehensive understanding of McLs' heterogeneity and how it impacts mucus physiology is urgently needed. When the role of airway mucus in the penetration and transmission of coronavirus (CoV) is considered, this understanding may also enable a better explanation and prediction of the CoV's behavior. Hence, in this Review, we summarize the variances of McLs among organs, health conditions, and experimental settings as well as recent advances in experimental measurements, data analysis, and model development for simulations.


Subject(s)
COVID-19 , Drug Delivery Systems , Humans , Mucus/physiology , SARS-CoV-2
19.
Ther Deliv ; 13(4): 205-209, 2022 04.
Article in English | MEDLINE | ID: covidwho-1887291

ABSTRACT

Graphical abstract [Formula: see text].


Subject(s)
Drug Delivery Systems
20.
Acta Biomater ; 148: 133-141, 2022 08.
Article in English | MEDLINE | ID: covidwho-1885570

ABSTRACT

Microneedles can realize the intradermal and transdermal delivery of drugs. However, most conventional microneedles made of metal, polymer and ceramics are unsuitable for the delivery of mRNA drugs that are fragile and temperature-sensitive. This study explores the usage of cryomicroneedles (CryoMNs) for the intradermal delivery of mRNA molecules. Taking luciferase mRNA as an example, we first optimize the formulation of CryoMNs to maximize mRNA stability. Later, in the mouse model, we compare the delivery efficiency with the conventional subcutaneous injection for both the luciferase mRNA and COVID-19 Comirnaty mRNA vaccines, where CryoMNs delivered mRNA vaccines successfully induce specific B-cell antibody, neutralizing activity and T-cell responses. STATEMENT OF SIGNIFICANCE: mRNA vaccines are fragile and temperature-sensitive, so they are mainly delivered by intramuscular injection that often causes pain and requires clinical expertise to immunize patients. Microneedles permit convenient, fast and safe vaccination. However, existing microneedle platforms are ineffective to protect the integrity of mRNA vaccines in fabrication, storage, and administration. This work utilizes cryomicroneedles (CryoMNs) technology to intradermally deliver mRNA. In the mouse model, CryoMNs are compared with the subcutaneous injection for the delivery efficiency of both the luciferase mRNA and COVID-19 Comirnaty mRNA vaccines, where CryoMNs delivered mRNA vaccines successfully produce specific B-cell antibodies, T-cell responses, and neutralizing activity. This work is expected to provide a new delivery strategy for the emerging mRNA therapeutics.


Subject(s)
COVID-19 , Animals , COVID-19/prevention & control , Drug Delivery Systems , Injections, Intradermal , Mice , Needles , RNA, Messenger/genetics , Vaccination
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