scholarly journals Repurposing Antiviral Protease Inhibitors Using Extracellular Vesicles for Potential Therapy of COVID-19

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 486 ◽  
Author(s):  
Santosh Kumar ◽  
Kaining Zhi ◽  
Ahona Mukherji ◽  
Kelli Gerth
Keyword(s):  
Side Effects ◽  
Protease Inhibitors ◽  
Extracellular Vesicles ◽  
Targeted Delivery ◽  
Critical Role ◽  
Drug Carriers ◽  
Antiviral Drugs ◽  
World Health ◽  
Therapeutic Window ◽  
High Dose

In January 2020, Chinese health agencies reported an outbreak of a novel coronavirus-2 (CoV-2) which can lead to severe acute respiratory syndrome (SARS). The virus, which belongs to the coronavirus family (SARS-CoV-2), was named coronavirus disease 2019 (COVID-19) and declared a pandemic by the World Health Organization (WHO). Full-length genome sequences of SARS-CoV-2 showed 79.6% sequence identity to SARS-CoV, with 96% identity to a bat coronavirus at the whole-genome level. COVID-19 has caused over 133,000 deaths and there are over 2 million total confirmed cases as of 15 April 2020. Current treatment plans are still under investigation due to a lack of understanding of COVID-19. One potential mechanism to slow disease progression is the use of antiviral drugs to either block the entry of the virus or interfere with viral replication and maturation. Currently, antiviral drugs, including chloroquine/hydroxychloroquine, remdesivir, and lopinavir/ritonavir, have shown effective inhibition of SARS-CoV-2 in vitro. Due to the high dose needed and narrow therapeutic window, many patients are experiencing severe side effects with the above drugs. Hence, repurposing these drugs with a proper formulation is needed to improve the safety and efficacy for COVID-19 treatment. Extracellular vesicles (EVs) are a family of natural carriers in the human body. They play a critical role in cell-to-cell communications. EVs can be used as unique drug carriers to deliver protease inhibitors to treat COVID-19. EVs may provide targeted delivery of protease inhibitors, with fewer systemic side effects. More importantly, EVs are eligible for major aseptic processing and can be upscaled for mass production. Currently, the FDA is facilitating applications to treat COVID-19, which provides a very good chance to use EVs to contribute in this combat.

scholarly journals Targeted Drug Delivery Systems for the Treatment of Glaucoma: Most Advanced Systems Review

Polymers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1742 ◽  
Author(s):  
Olga Cegielska ◽  
Paweł Sajkiewicz
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Targeted Delivery ◽  
Drug Targets ◽  
Drug Delivery Systems ◽  
Release Kinetics ◽  
Controlled Drug Release ◽  
Drug Carriers ◽  
Delivery Systems ◽  
Drug Bioavailability

Each year, new glaucoma drug delivery systems are developed. Due to the chronic nature of the disease, it requires the inconvenient daily administration of medications. As a result of their elution from the eye surface and penetration to the bloodstream through undesired permeation routes, the bioavailability of active compounds is low, and systemic side effects occur. Despite numerous publications on glaucoma drug carriers of controlled drug release kinetics, only part of them consider drug permeation routes and, thus, carriers’ location, as an important factor affecting drug delivery. In this paper, we try to demonstrate the importance of the delivery proximal to glaucoma drug targets. The targeted delivery can significantly improve drug bioavailability, reduce side effects, and increase patients’ compliance compared to both commercial and scientifically developed formulations that can spread over the eye surface or stay in contact with conjunctival sac. We present a selection of glaucoma drug carriers intended to be placed on cornea or injected into the aqueous humor and that have been made by advanced materials using hi-tech forming methods, allowing for effective and convenient sustained antiglaucoma drug delivery.

scholarly journals Melittin-Based Nano-Delivery Systems for Cancer Therapy

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 118
Author(s):  
Anqi Wang ◽  
Yuan Zheng ◽  
Wanxin Zhu ◽  
Liuxin Yang ◽  
Yang Yang ◽  
...  
Keyword(s):  
Side Effects ◽  
Cancer Therapy ◽  
Hemolytic Activity ◽  
Targeted Delivery ◽  
Lipid Membranes ◽  
Drug Carriers ◽  
Delivery Systems ◽  
Cationic Polymers ◽  
Toxicological Effects ◽  
Strong Surface

Melittin (MEL) is a 26-amino acid polypeptide with a variety of pharmacological and toxicological effects, which include strong surface activity on cell lipid membranes, hemolytic activity, and potential anti-tumor properties. However, the clinical application of melittin is restricted due to its severe hemolytic activity. Different nanocarrier systems have been developed to achieve stable loading, side effects shielding, and tumor-targeted delivery, such as liposomes, cationic polymers, lipodisks, etc. In addition, MEL can be modified on nano drugs as a non-selective cytolytic peptide to enhance cellular uptake and endosomal/lysosomal escape. In this review, we discuss recent advances in MEL’s nano-delivery systems and MEL-modified nano drug carriers for cancer therapy.

Weekly high-dose leucovorin versus low-dose leucovorin combined with fluorouracil in advanced colorectal cancer: results of a randomized multicenter trial. Study Group for Palliative Treatment of Metastatic Colorectal Cancer Study Protocol 1.

1996 ◽  
Vol 14 (8) ◽  
pp. 2274-2279 ◽  
Author(s):  
E Jäger ◽  
M Heike ◽  
H Bernhard ◽  
O Klein ◽  
G Bernhard ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Side Effects ◽  
Metastatic Colorectal Cancer ◽  
Low Dose ◽  
Multicenter Trial ◽  
World Health ◽  
High Dose ◽  
Who Grade ◽  
Group A ◽  
Group B

PURPOSE To determine the most effective dose of leucovorin (folinic acid [FA]) within a weekly bolus fluorouracil (FU) schedule, we conducted a randomized multicenter trial to compare therapeutic effects and toxicity of high-dose FA versus low-dose FA combined with FU at equal doses in both treatment groups. PATIENTS AND METHODS Patients with measurable inoperable or metastatic colorectal cancer were randomized to receive weekly FU 500 mg/m2 by intravenous (IV) bolus combined with high-dose FA 500 mg/m2 (group A) or low-dose FA 20 mg/m2 (group B) by 2-hour infusion. RESULTS Of 291 assessable patients (group A, n = 148; group B, n = 143), we observed, in group A, complete response (CR)/partial response (PR) in 32 (21.6%), no change (NC) in 64 (43.2%), and progressive disease (PD) in 52 (35.1%); and in group B, CR/PR in 25 (17.5%), NC in 63 (44.1%), and PD in 55 (38.5%). The median response duration was 24.8 weeks in group A and 23.1 weeks in group B. Median progression-free intervals were 29.3 weeks (group A) and 30 weeks (group B). The median survival time was 55.1 weeks in group A and 54.1 weeks in group B. Overall toxicity was moderate. Mild nausea and vomiting, and stomatitis were common side effects in both groups. The incidence of World Health Organization (WHO) grade III/IV diarrhea was significantly higher in group A (40 v 23 patients). Severe side effects were observed only in a minority of patients in both arms. WHO grade IV diarrhea was observed in seven patients: four in group A and three in group B. The rate of toxicity-related adjustments of dose and schedule was comparable in both groups. CONCLUSION High-dose FA/FU is not superior to low-dose FA/FU within a weekly treatment schedule. Response rates and survival were comparable in both treatment arms. Treatment-related toxicity was higher in group A (high-dose FA). Therefore, low-dose FA combined with weekly FU may be considered the preferred treatment for metastatic colorectal cancer.

scholarly journals Nano Based Approach for the Treatment of Neglected Tropical Diseases

2021 ◽  
Vol 3 ◽  
Author(s):  
Sureshbabu Ram Kumar Pandian ◽  
Theivendren Panneerselvam ◽  
Parasuraman Pavadai ◽  
Saravanan Govindaraj ◽  
Vigneshwaran Ravishankar ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Targeted Delivery ◽  
Drug Delivery Systems ◽  
Neglected Tropical Diseases ◽  
Delivery Systems ◽  
World Health ◽  
Tropical Diseases ◽  
Treatment Research ◽  
Pharmaceutical Industries

Neglected tropical diseases (NTDs) afflict more than one billion peoples in the world’s poorest countries. The World Health Organization (WHO) has recorded seventeen NTDs in its portfolio, mainly caused by bacterial, protozoal, parasitic, and viral infections. Each of the NTDs has its unique challenges on human health such as interventions for control, prevention, diagnosis, and treatment. Research for the development of new drug molecules against NTDs has not been undertaken by pharmaceutical industries due to high investment and low-returns, which results in limited chemotherapeutics in the market. In addition, conventional chemotherapies for the treatment of NTDs are unsatisfactory due to its low efficacy, increased drug resistance, short half-life, potential or harmful fatal toxic side effects, and drug incompetence to reach the site of parasite infection. In this context, active chemotherapies are considered to be re-formulated by overcoming these toxic side effects via a tissue-specific targeted drug delivery system. This review mainly emphasizes the recent developments of nanomaterial-based drug delivery systems for the effective treatment of NTDs especially sleeping sickness, leishmaniasis, chagas disease, soil-transmitted helminthiasis, african trypanosomiasis and dengue. Nanomaterials based drug delivery systems offer enhanced and effective alternative therapy through the re-formulation approach of conventional drugs into site-specific targeted delivery of drugs.

Evaluating the adverse effects of melphalan formulations

2018 ◽  
Vol 25 (7) ◽  
pp. 1631-1637 ◽  
Author(s):  
Elaine Xiang ◽  
Jian Ni ◽  
Brett Glotzbecker ◽  
Jacob Laubach ◽  
Robert Soiffer ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Side Effects ◽  
Adverse Effects ◽  
Propylene Glycol ◽  
World Health ◽  
High Dose ◽  
Cell Transplant ◽  
Primary Therapy ◽  
High Dose Melphalan

Introduction For multiple myeloma patients who respond to primary therapy, autologous hematopoietic stem cell transplant (HSCT) is considered standard of care with high-dose melphalan for transplant candidates. There are now two different melphalan formulations available, including a propylene glycol containing (PG-MEL) product and a propylene glycol-free (PG-free MEL) product. Although considered bioequivalent, there remains limited literature directly evaluating the adverse events between the two agents. We seek to assess the tolerability and severity of side effects between the two formulations in a real-life practice setting. Methods A retrospective, descriptive analysis was conducted of multiple myeloma patients who received autologous stem cell conditioning with either melphalan formulation when dosed at 100 mg/m2/dose for two consecutive doses. The primary outcome was the assessment of tolerability and severity of side effects. Tolerability was split into four major categories including hematologic toxicity, gastrointestinal toxicity, renal toxicity, and highest recorded mucositis grade. Results There were a total of 78 patients who received a melphalan preparation during the study. The median time to myeloablation and neutrophil engraftment was five and seven days post-HSCT, respectively, for all patients. Patients who received PG-free MEL were less likely to develop mucositis, with 22 (56%) reported highest grade 0, defined by World Health Organization oral toxicity scale, compared to those who received PG-MEL (33%), p = 0.04. Conclusion There were minimal differences in tolerability or side effects observed between PG-free MEL and PG-MEL. These data may assist in better understanding the anticipated adverse effects of a high-dose melphalan conditioning therapy.

scholarly journals POTENTIAL PHYTOCONSTITUENTS FROM NATURAL PRODUCTS FOR COMBATING AGAINST CORONAVIRUS DISEASE-19 (SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS‐2) - A REVIEW

2021 ◽  
pp. 8-18
Author(s):  
CHANDRASEKAR R ◽  
SIVAGAMI B ◽  
SATHEESH KUMAR G
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Medicinal Plants ◽  
Severe Acute Respiratory Syndrome ◽  
Viral Infection ◽  
Viral Infections ◽  
Critical Role ◽  
Antiviral Drug ◽  
World Health ◽  
Human Beings

Coronavirus called as coronavirus diseases (COVID)-19 (severe acute respiratory syndrome coronavirus [SARS‐CoV]‐2) is a viral infection which is spreading to a great extent and affecting many people worldwide, many developed and developing countries are severely affected by the virus. The World Health Organization (WHO) is taking serious preventive measures to stop this viral infection worldwide. The coronavirus is a big threat to human beings and controlling the emerging viral infections is a global concern. Antiviral drug such as Remdesivir has been approved by the FDA, but combating against these viral infections is a great challenge to scientists and researchers with the available few antiviral drugs due to severe side effects and toxicity. Many drugs such as hydroxy chloroquin, Remdesivir, and vaccines have been recommended for combating this virus. Few Polyherbal formulations and Ayurvedic formulations containing antiviral phytoconstituents have been recommended to boost the immunity. Some drugs and phytoconstituents are under different phases of human clinical trials. The currently available synthetic drugs and vaccines for the treatment of viral infections have severe side effects. Medicinal plants play a critical role in treating viral infections by developing immunity against viral diseases. Some medicinal plants which were used as antipyretic, analgesic, and anti-inflammatory activity helped in treating various diseases and viral infections. Many plants contain flavonoids such as quercetin, luteolin, apigenin, and polyphenols such as thymoquinone, phytosteroids such as cucurbitacin and others which may likely to act as antioxidants and immunomodulatory that can fight against COVID-19. The current review provides information on phytochemical constituents present in medicinal plants, their mechanism of action, in silico molecular docking studies and human clinical trials to treat viral disorders.

scholarly journals Exploiting the Natural Properties of Extracellular Vesicles in Targeted Delivery towards Specific Cells and Tissues

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1022 ◽  
Author(s):  
Pablo Lara ◽  
Alan B. Chan ◽  
Luis J. Cruz ◽  
Andrew F. G. Quest ◽  
Marcelo J. Kogan
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Extracellular Vesicles ◽  
Targeted Delivery ◽  
Cell Regeneration ◽  
Natural Properties ◽  
Cargo Delivery ◽  
Cell Sources ◽  
Potential Risks ◽  
Diagnosis Of Diseases

Extracellular vesicles (EVs) are important mediators of intercellular communication that participate in many physiological/pathological processes. As such, EVs have unique properties related to their origin, which can be exploited for drug delivery applications in cell regeneration, immunosuppression, inflammation, cancer treatment or cardioprotection. Moreover, their cell-like membrane organization facilitates uptake and accumulation in specific tissues and organs, which can be exploited to improve selectivity of cargo delivery. The combination of these properties with the inclusion of drugs or imaging agents can significantly improve therapeutic efficacy and selectivity, reduce the undesirable side effects of drugs or permit earlier diagnosis of diseases. In this review, we will describe the natural properties of EVs isolated from different cell sources and discuss strategies that can be applied to increase the efficacy of targeting drugs or other contents to specific locations. The potential risks associated with the use of EVs will also be addressed.

scholarly journals An overview of characterizations and applications of proniosomal drug delivery system

2021 ◽  
Vol 7 (2) ◽  
pp. 025-034
Author(s):  
Minakshee G. Nimbalwar ◽  
Bhushan R. Gudalwar ◽  
Wrushali A. Panchale ◽  
Ashish B. Wadekar ◽  
Jagdish V. Manwar ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Drug Delivery System ◽  
Delivery System ◽  
Targeted Delivery ◽  
Drug Carriers ◽  
Water Soluble ◽  
Ionic Surfactant ◽  
Poorly Soluble Drugs ◽  
Poorly Soluble

Proniosomal drug delivery system is a stable provesicular system in nanotechnology to overcome the drawbacks associated with other vesicular systems. These are water-soluble pro-vesicular drug carriers coated with a non-ionic surfactant which on hydration give niosomes. The system is encapsulated and shows a systemic and targeted delivery of poorly soluble drugs with increased bioavailability and decreased side effects. Here we have covered characterizations and applications of the proniosomal drug delivery system.

An oral high dose of cholecalciferol restores vitamin D status in deficient postmenopausal HIV-1 infected women independently of protease inhibitors therapy

2015 ◽  
Author(s):  
Jessica Pepe ◽  
Ivano Mezzaroma ◽  
Alessandra Fantauzzi ◽  
Mario Falciano ◽  
Alessandra Salotti ◽  
...  
Keyword(s):  
Vitamin D ◽  
Protease Inhibitors ◽  
High Dose ◽  
Vitamin D Status ◽  
Hiv 1

Role of novel drug delivery systems in coronavirus disease-2019 (covid-19): time to act now

2020 ◽  
Vol 17 ◽  
Author(s):  
Neeraj Mittal ◽  
Varun Garg ◽  
Sanjay Kumar Bhadada ◽  
O. P. Katare
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
World Health ◽  
Ongoing Research ◽  
Standard Drug ◽  
Corona Virus ◽  
Novel Drug

: The corona virus disease 2019 (COVID-19) has found its roots from Wuhan (China). COVID-19 is caused by a novel corona virus SARS-CoV2, previously named as 2019-nCoV. COVID-19 has spread across the globe and declared as pandemic by World health organization (WHO) on 11th March, 2020. Currently, there is no standard drug or vaccine available for the treatment, so repurposing of existing drugs is the only solution. Novel drug delivery systems (NDDS) will be boon for the repurposing of drugs. The role of various NDDS in repurposing of existing drugs for treatment of various viral diseases and their relevance in COVID-19 has discussed in this paper. It focuses on the currently ongoing research in the implementation of NDDS in COVID-19. Moreover it describes the role of NDDS in vaccine development for COVID-19. This paper also emphasizes how NDDS will help to develop the improved delivery systems (dosage forms) of existing therapeutic agents and also explore the new insights to find out the void spaces for a potential targeted delivery. So in these tough times, NDDS and nanotechnology can be a safeguard to humanity.

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