Nanoparticles in the clinic: An update post COVID-19 vaccines.
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ABSTRACT:
SUBMITTER: Anselmo AC
PROVIDER: S-EPMC8420572 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:COVID-19 vaccines have been developed with unprecedented speed which would not have been possible without decades of fundamental research on delivery nanotechnology. Lipid-based nanoparticles have played a pivotal role in the successes of COVID-19 vaccines and many other nanomedicines, such as Doxil® and Onpattro®, and have therefore been considered as the frontrunner in nanoscale drug delivery systems. In this review, we aim to highlight the progress in the development of these lipid nanoparticles for various applications, ranging from cancer nanomedicines to COVID-19 vaccines. The lipid-based nanoparticles discussed in this review are liposomes, niosomes, transfersomes, solid lipid nanoparticles, and nanostructured lipid carriers. We particularly focus on the innovations that have obtained regulatory approval or that are in clinical trials. We also discuss the physicochemical properties required for specific applications, highlight the differences in requirements for the delivery of different cargos, and introduce current challenges that need further development. This review serves as a useful guideline for designing new lipid nanoparticles for both preventative and therapeutic vaccines including immunotherapies.
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Project description:Nanoparticle drug delivery systems have been used in the clinic since the early 1990's. Since that time, the field of nanomedicine has evolved alongside growing technological needs to improve the delivery of various therapeutics. Over these past decades, newer generations of nanoparticles have emerged that are capable of performing additional delivery functions that can enable treatment via new therapeutic modalities. In the current clinical landscape, many of these new generation nanoparticles have reached clinical trials and have been approved for various indications. In the first issue of Bioengineering & Translational Medicine in 2016, we reviewed the history, current clinical landscape, and clinical challenges of nanoparticle delivery systems. Here, we provide a 3 year update on the current clinical landscape of nanoparticle drug delivery systems and highlight newly approved nanomedicines, provide a status update on previous clinical trials, and highlight new technologies that have recently entered the clinic.
| S-EPMC6764803 | biostudies-literature
Project description:Since its inception in late December 2020 in China, novel coronavirus has affected the global socio-economic aspect. Currently, the world is seeking safe and effective treatment measures against COVID-19 to eradicate it. Many established drug molecules are tested against SARS-CoV-2 as a part of drug repurposing where some are proved effective for symptomatic relief while some are ineffective. Drug repurposing is a practical strategy for rapidly developing antiviral agents. Many drugs are presently being repurposed utilizing basic understanding of disease pathogenesis and drug pharmacodynamics, as well as computational methods. In the present situation, drug repurposing could be viewed as a new treatment option for COVID-19. Several new drug molecules and biologics are engineered against SARS-CoV-2 and are under different stages of clinical development. A few biologics drug products are approved by USFDA for emergency use in the covid management. Due to continuous mutation, many of the approved vaccines are not much efficacious to render the individual immune against opportunistic infection of SARS-CoV-2 mutants. Hence, there is a strong need for the cogent therapeutic agent for covid management. In this review, a consolidated summary of the therapeutic developments against SARS-CoV-2 are depicted along with an overview of effective management of post COVID-19 complications.
| S-EPMC8813675 | biostudies-literature
Project description:The coronavirus disease (COVID-19) is caused by a positive-stranded RNA virus called severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), belonging to the Coronaviridae family. This virus originated in Wuhan City, China, and became the cause of a multiwave pandemic that has killed 3.46 million people worldwide as of May 22, 2021. The havoc intensified with the emergence of SARS-CoV-2 variants (B.1.1.7; Alpha, B.1.351; Beta, P.1; Gamma, B.1.617; Delta, B.1.617.2; Delta-plus, B.1.525; Eta, and B.1.429; Epsilon etc.) due to mutations generated during replication. More variants may emerge to cause additional pandemic waves. The most promising approach for combating viruses and their emerging variants lies in prophylactic vaccines. Several vaccine candidates are being developed using various platforms, including nucleic acids, live attenuated virus, inactivated virus, viral vectors, and protein-based subunit vaccines. In this unprecedented time, 12 vaccines against SARS-CoV-2 have been phased in following WHO approval, 184 are in the preclinical stage, and 100 are in the clinical development process. Many of them are directed to elicit neutralizing antibodies against the viral spike protein (S) to inhibit viral entry through the ACE-2 receptor of host cells. Inactivated vaccines, to the contrary, provide a wide range of viral antigens for immune activation. Being an intracellular pathogen, the cytotoxic CD8+ T Cell (CTL) response remains crucial for all viruses, including SARS-CoV-2, and needs to be explored in detail. In this review, we try to describe and compare approved vaccines against SARS-CoV-2 that are currently being distributed either after phase III clinical trials or for emergency use. We discuss immune responses induced by various candidate vaccine formulations; their benefits, potential limitations, and effectiveness against variants; future challenges, such as antibody-dependent enhancement (ADE); and vaccine safety issues and their possible resolutions. Most of the current vaccines developed against SARS-CoV-2 are showing either promising or compromised efficacy against new variants. Multiple antigen-based vaccines (multivariant vaccines) should be developed on different platforms to tackle future variants. Alternatively, recombinant BCG, containing SARS-CoV-2 multiple antigens, as a live attenuated vaccine should be explored for long-term protection. Irrespective of their efficacy, all vaccines are efficient in providing protection from disease severity. We must insist on vaccine compliance for all age groups and work on vaccine hesitancy globally to achieve herd immunity and, eventually, to curb this pandemic.
| S-EPMC8461057 | biostudies-literature
Project description:Once the World Health Organization (WHO) declared the COVID-19 (Coronavirus Infectious Disease-19) outbreak to be pandemic, massive efforts have been launched by researchers around the globe to combat this emerging infectious disease. Strategies that must be investigated such as expanding testing capabilities, developing effective medicines, as well as developing safe and effective vaccines for COVID-19 disease that produce long-lasting immunity to human system. Now-a-days, bio-sensing, medication delivery, imaging, and antimicrobial treatment are just a few of the medical applications for nanoparticles (NPs). Since the early 1990s, nanoparticle drug delivery methods have been employed in clinical trials. Since then, the discipline of nanomedicine has evolved in tandem with expanding technological demands to better medicinal delivery. Newer generations of NPs have emerged in recent decades that are capable of performing additional delivery tasks, allowing for therapy via novel therapeutic modalities. Many of these next generation NPs and associated products have entered clinical trials and have been approved for diverse indications in the present clinical environment. For systemic applications, NPs or nanomedicine-based drug delivery systems have substantial benefits over their non-formulated and free drug counterparts. Nanoparticle systems, for example, are capable of delivering medicines and treating parts of the body that are inaccessible to existing delivery systems. As a result, NPs medication delivery is one of the most studied preclinical and clinical systems. NPs-based vaccines delivering SARS-CoV-2 antigens will play an increasingly important role in prolonging or improving COVID-19 vaccination outcomes. This review provides insights about employing NPs-based drug delivery systems for the treatment of COVID-19 to increase the bioavailability of current drugs, reducing their toxicity, and to increase their efficiency. This article also exhibits their capability and efficacy, and highlighting the future aspects and challenges on nanoparticle products in clinical trials of COVID-19.
| S-EPMC9359769 | biostudies-literature
Project description:Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk-factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data, and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.
2022-02-01 | E-MTAB-10129 | biostudies-arrayexpress
Project description:BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has challenged healthcare globally. An acute increase in the number of hospitalized patients has necessitated a rigorous reorganization of hospital care, thereby creating circumstances that previously have been identified as facilitating prescribing errors (PEs), e.g. a demanding work environment, a high turnover of doctors, and prescribing beyond expertise. Hospitalized COVID-19 patients may be at risk of PEs, potentially resulting in patient harm. We determined the prevalence, severity, and risk factors for PEs in post-COVID-19 patients, hospitalized during the first wave of COVID-19 in the Netherlands, 3 months after discharge.MethodsThis prospective observational cohort study recruited patients who visited a post-COVID-19 outpatient clinic of an academic hospital in the Netherlands, 3 months after COVID-19 hospitalization, between June 1 and October 1 2020. All patients with appointments were eligible for inclusion. The prevalence and severity of PEs were assessed in a multidisciplinary consensus meeting. Odds ratios (ORs) were calculated by univariate and multivariate analysis to identify independent risk factors for PEs.ResultsNinety-eight patients were included, of whom 92% had ≥1 PE and 8% experienced medication-related harm requiring an immediate change in medication therapy to prevent detoriation. Overall, 68% of all identified PEs were made during or after the COVID-19 related hospitalization. Multivariate analyses identified ICU admission (OR 6.08, 95% CI 2.16-17.09) and a medical history of COPD / asthma (OR 5.36, 95% CI 1.34-21.5) as independent risk factors for PEs.ConclusionsPEs occurred frequently during the SARS-CoV-2 pandemic. Patients admitted to an ICU during COVID-19 hospitalization or who had a medical history of COPD / asthma were at risk of PEs. These risk factors can be used to identify high-risk patients and to implement targeted interventions. Awareness of prescribing safely is crucial to prevent harm in this new patient population.
| S-EPMC8897739 | biostudies-literature
Project description:Background and aim of the workThe coronavirus disease-19 (COVID-19) outbreak is posing considerable challenges to healthcare systems and societies worldwide. While the knowledge on the acute phase of the disease has rapidly expanded, little is known on the consequences of COVID-19 following clinical remission. We set up a multidisciplinary COVID-19 follow-up outpatient clinic to identify and address the clinical needs of COVID-19 survivors. Here we describe the features of our follow-up programme.MethodsThe multidisciplinary assessment comprises a complete physical examination, respiratory evaluation (peripheral oxygen saturation, respiratory rate, dyspnoea assessment, lung ultrasound and pulmonary function), cardiovascular assessment (electrocardiography, echocardiography), nutritional assessment (anthropometrics, mini Nutritional Assessment screening tool), neurological examination including cognitive tests, and mental health assessment. All data are prospectively collected, and blood is sampled for biobanking.ResultsSince 7 April to 5 June, 2020, 453 out of the 1388 COVID-19 survivors managed at our University Hospital have been evaluated at the Outpatient COVID-19 Follow-up Clinic. The characteristics of the follow-up cohort are similar to those of the whole cohort of COVID-19 in terms of demographics, comorbidities, and COVID-19 severity upon ED presentation, indicating that the follow-up cohort is representative of the whole cohort.ConclusionsContinuous patient monitoring might give an answer to the numerous unsolved questions about what comes next in this pandemic and beyond. This will help physicians and researchers establish strategies to face future pandemics and develop preventative and therapeutic strategies for similar hyperinflammatory conditions.
| S-EPMC8023087 | biostudies-literature
Project description:Coronavirus disease (COVID-19) was first reported in December 2019, Hubei Province, China. As on 9th December 2021, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has affected 266018810 people worldwide with 5265092 deaths. The outbreak of COVID-19 pandemic has caused severe public health crisis across the world. Nucleic acids have been emerging as potential drugs to treat a variety of diseases. Lipid nanoparticles (LNPs) have great potential to deliver nucleic acids including mRNAs. The two mRNA-based vaccines namely the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) have been given emergency use authorization (EUA) by the US-FDA to prevent SARS-CoV-2 caused COVID-19 and the vaccines were developed using LNPs. This article focuses on the potential application of LNPs in the development and delivery of mRNA vaccines for COVID-19.
| S-EPMC9238147 | biostudies-literature
Project description:Coronavirus Disease 2019 named as COVID-19 imposing a huge burden on public health as well as global economies, is caused by a new strain of betacoronavirus named as SARS-CoV-2. The high transmission rate of the virus has resulted in current havoc which highlights the need for a fast and effective approach either to prevent or treat the deadly infection. Development of vaccines can be the most prominent approach to prevent the virus to cause COVID-19 and hence will play a vital role in controlling the spread of the virus and reducing mortality. The virus uses its spike proteins for entering into the host by interacting with a specific receptor called angiotensin converting enzyme-2 (ACE2) present on the surface of alveolar cells in the lungs. Researchers all over the world are targeting the spike protein for the development of potential vaccines. Here, we discuss the immunopathological basis of vaccine designing that can be approached for vaccine development against SARS-CoV-2 infection and different platforms that are being used for vaccine development. We believe this review will increase our understanding of the vaccine designing against SARS-CoV-2 and subsequently contribute to the control of SARS-CoV-2 infections. Also, it gives an insight into the current status of vaccine development and associated outcomes reported at different phases of trial.
| S-EPMC7685956 | biostudies-literature