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Nanotoxicology Apr 2024Amphotericin B (AmB) is a broad-spectrum therapeutic and effective drug, but it has serious side effects of toxicity and solubility. Therefore, reducing its toxicity... (Review)
Review
Amphotericin B (AmB) is a broad-spectrum therapeutic and effective drug, but it has serious side effects of toxicity and solubility. Therefore, reducing its toxicity should be considered in therapeutic applications. Nanotechnology has paved the way to improve drug delivery systems and reduce toxicity. The present study, for the first time, comprehensively reviews the studies from 2011 to 2023 on reducing the toxicity of AmB. The findings showed that loading AmB with micellar structures, nanostructured lipid carriers, liposomes, emulsions, poly lactide-co-glycolide acid, chitosan, dendrimers, and other polymeric nanoparticles increases the biocompatibility and efficacy of the drug and significantly reduces toxicity. In addition, modified carbon nanoparticles (including graphene, carbon nanotubes, and carbon dots) with positively charged amine groups, PEI, and other components showed favorable drug delivery properties. Uncoated and coated magnetic nanoparticles and silver NPs-AmB composites had less cytotoxicity and more antifungal activity than free AmB. Citrate-reduced GNPs and lipoic acid-functionalized GNPs were also effective nanocarriers to reduce AmB cytotoxicity and improve anti-leishmania efficacy. In addition, zinc oxide-NPs and PEGylated zinc oxide-NPs showed favorable antifungal activity and negligible toxicity. According to a review study, carbon-based nanoparticles, metal nanoparticles, and especially polymer nanoparticles caused some reduction in the toxicity and improved solubility of AmB in water. Overall, considering the discussed nanocarriers, further research on the application of nanotechnology as a cost-effective candidate to improve the efficiency and reduce the cytotoxicity of AmB is recommended.
PubMed: 38646931
DOI: 10.1080/17435390.2024.2340467 -
Nutrition Research (New York, N.Y.) Aug 2021Clinical trials have reported that a four-oil intravenous lipid emulsion (SMOFlipid) play a positive role in immune function, but showed inconsistent outcomes compared... (Meta-Analysis)
Meta-Analysis
A four-oil intravenous lipid emulsion improves markers of liver function, triglyceride levels and shortens length of hospital stay in adults: a systematic review and meta-analysis.
Clinical trials have reported that a four-oil intravenous lipid emulsion (SMOFlipid) play a positive role in immune function, but showed inconsistent outcomes compared to other lipid emulsions. A systematic review and meta-analysis was conducted to evaluate the effect of SMOFlipid on liver function, triglycerides (TG), inflammatory markers, and clinical outcomes in hospitalized adults after short-term use compared to others. A search of the PubMed, Medline, Embase, China National Knowledge Infrastructure, and Wanfang databases was performed to identify the included randomized controlled trials. Trials with adults who were administrated a short-term course of SMOFlipid were included. A meta-analysis on liver function markers, TG, inflammatory markers, and clinical outcomes was conducted. A total of 18 randomized controlled trials with 1188 patients were included. Compared to other lipid emulsions, SMOFlipid was associated with a significant reduction in ALT, AST, γ-glutamyltransferase, total bilirubin, TG, C-reactive protein and length of hospital stay. No effect on serum interleukin-6 levels or adverse events were observed. For adult patients, our meta-analysis indicated that SMOFlipid may be beneficial to the liver and prone to prevent hyperlipidemia. The SMOFlipid also shortened length of hospital stay.
Topics: Adult; Fat Emulsions, Intravenous; Fatty Acids, Omega-3; Fish Oils; Humans; Hyperlipidemias; Inflammation; Length of Stay; Liver; Olive Oil; Parenteral Nutrition; Plant Oils; Soybean Oil; Triglycerides
PubMed: 34157593
DOI: 10.1016/j.nutres.2021.05.003 -
European Review For Medical and... Jun 2020Intravenous lipid emulsions (ILE) were developed many decades ago to supply nutritional requirements to patients unable to obtain adequate enteral nutrition. The utility...
OBJECTIVE
Intravenous lipid emulsions (ILE) were developed many decades ago to supply nutritional requirements to patients unable to obtain adequate enteral nutrition. The utility of ILE was extended to therapeutics, facilitating the delivery of drugs. More recently, the potential for ILE to act as an antidote for inversion of drug toxicity has been recognized. This review aims to summarize the literature on ILE therapy as an antidote. Suggested mechanisms of action, safety profile, and recommendations on the administration of ILE in cases of drug intoxication are highlighted.
MATERIALS AND METHODS
A complete literature survey was performed using the PubMed database search to collect available information regarding mechanisms of ILE action as an antidote, ILE administration for drug toxicity, and presentation of adverse events.
RESULTS
A total of 102 studies met the selection criteria for inclusion in the review. Mainly used for local anesthetics toxicity, ILE therapy has been expanded in clinical toxicology involving overdose treatment of drugs other than local anesthetics. Partitioning in a lipid phase of fat droplets is a mechanism named the lipid sink phenomenon that has primarily been described to explain this action of ILE and remains the most widely accepted. At the same time, recent research has also revealed several molecular mechanisms that may contribute to ILE efficacy.
CONCLUSIONS
ILE therapy comprises a recognized approach in clinical toxicology. Due to the lack of randomized clinical trials, recommendations on administration are based on animal studies and published cases. Thus, the constantly increased knowledge about ILE therapy supports the need for a detailed appraisal.
Topics: Anesthetics, Local; Animals; Antidotes; Drug-Related Side Effects and Adverse Reactions; Fat Emulsions, Intravenous; Humans
PubMed: 32633409
DOI: 10.26355/eurrev_202006_21708 -
Journal of the European Academy of... Mar 2023Prophylactic application of emollients has been an effective strategy against infant atopic dermatitis (AD); however, the difference of different emollients is unknown.... (Meta-Analysis)
Meta-Analysis
Prophylactic application of emollients has been an effective strategy against infant atopic dermatitis (AD); however, the difference of different emollients is unknown. We performed this network meta-analysis to compare different emollients in preventing infant AD. A systematic search was performed in PubMed, EMBASE and Cochrane library to identify relevant studies from their inception through 28 February, 2022. We evaluated the quality of eligible studies using the Cochrane risk of bias assessment tool. Data analysis was performed using STATA 14.0. Eleven studies were included for data analysis. Direct meta-analysis suggested that early application of emollients effectively prevented AD development in high-risk infants (risk ratio [RR], 0.64; 95% confidence interval [CI], 0.47 to 0.88). Network meta-analysis suggested that emollient emulsion might the better option for preventing infant AD development, with a surface under the cumulative ranking curve (SUCRA) of 82.6% for all populations, 78.0% for high-risk populations and 79.2% for populations with food sensitization. Moreover, subjects receiving emollients more frequently experienced adverse events. Overall, early application of emollients is an effective strategy for preventing AD development in high-risk infants and emollient emulsion may be the optimal type. Future study with well-designed and large scale are warranted to validate our findings.
Topics: Humans; Infant; Dermatitis, Atopic; Emollients; Emulsions; Network Meta-Analysis; Risk Factors
PubMed: 36415973
DOI: 10.1111/jdv.18688 -
Systematic review of topical diclofenac for the treatment of acute and chronic musculoskeletal pain.Current Medical Research and Opinion Apr 2020The objective was to systematically review the efficacy and safety of topical diclofenac in both acute and chronic musculoskeletal pain in adults. We used standard...
The objective was to systematically review the efficacy and safety of topical diclofenac in both acute and chronic musculoskeletal pain in adults. We used standard Cochrane methods. Searches were conducted in MEDLINE, EMBASE and The Cochrane Register of Studies; date of the final search was November 2018. Included studies were randomized, double blinded, with ten or more participants per treatment arm. The primary outcome of "clinical success" was defined as participant-reported reduction in pain of at least 50%. Details of adverse events (AEs) were recorded. For acute pain, 23 studies (5170 participants) were included. Compared to placebo, number needed to treat (NNT) for different formulations were as follows: diclofenac plaster, 4.7 (95% CI 3.7-6.5); diclofenac plaster with heparin, 7.4 (95% CI 4.6-19); and diclofenac Emulgel, 1.8 (95% CI 1.5-2.1). 4.1% (78/1919) reported a local AE. For chronic pain, 21 studies (26 publications) with 5995 participants were included. Formulations included gel, solution with or without DMSO, emulsion and plaster. A clinical success rate of ∼60% (NNT 9.5 [95% CI 7-14.7]) was achieved with a variety of formulations. Local AEs (∼14%) were similar for both diclofenac and placebo. This systematic review of 11,000+ participants demonstrates that topical diclofenac is effective for acute pain, such as sprains, with minimal AEs. The effectiveness of topical diclofenac was also demonstrated in chronic musculoskeletal pain but with a higher NNT (worse) compared with acute pain. Formulation does play a part in effectiveness but needs further studies.
Topics: Acute Pain; Administration, Topical; Anti-Inflammatory Agents, Non-Steroidal; Chronic Pain; Diclofenac; Humans; Musculoskeletal Pain; Randomized Controlled Trials as Topic
PubMed: 31944135
DOI: 10.1080/03007995.2020.1716703 -
Current Reviews in Clinical and... Nov 2022Acanthamoeba is one of the opportunistic parasites with a global prevalence. Currently, due to the side effects and the emergence of drug resistance to this parasite,...
BACKGROUND
Acanthamoeba is one of the opportunistic parasites with a global prevalence. Currently, due to the side effects and the emergence of drug resistance to this parasite, much research has been performed on the use of nano-drugs to treat Acanthamoeba-caused diseases. Therefore, this systematic review study aims to evaluate new strategies for treating diseases caused by Acanthamoeba based on nanoparticles (NPs).
METHODS
We designed a systematic review based on the articles published in English between 2000 and 2022. Our search strategy was based on syntax and specific tags for each database, including ScienceDirect, PubMed, Scopus, Ovid, and Cochrane. From the articles, those that had inclusion criteria were selected, and their data were extracted and analyzed.
RESULTS
In this study, 26 studies were selected. Metallic nanoparticles were mostly used against the Acanthamoeba species (80.7%). 19.2% of the studies used polymeric nanoparticles, and 3.8% used emulsion nanoparticles. Most studies (96.1%) were performed in vitro, and only one study (3.8%) was carried out in vivo. Silver NPs were the most used metallic nanoparticles in the studies. The best effect of the anti-Acanthamoeba compound was observed for green synthesized nanoparticles based on stabilization by plant gums, loaded with citrus fruits flavonoids hesperidin (HDN) and naringin (NRG) with a 100% growth inhibition at a concentration of 50 μg/mL.
CONCLUSION
This study showed that chlorhexidine and other plant metabolites loaded with silver and gold nanoparticles increase the anti-Acanthambae activity of these nanoparticles. However, green synthesized nanoparticles based on stabilization by plant gums, loaded with citrus fruits flavonoids hesperidin (HDN) and naringin (NRG), showed the best anti-Acanthambae effect. Nevertheless, further studies should be performed to determine their safety for human use.
PubMed: 36372923
DOI: 10.2174/2772432818666221111155119 -
Drug Design, Development and Therapy 2020Microemulsions drug delivery systems (MDDS) have been known to increase the bioavailability of hydrophobic drugs. The main challenge of the MDDS is the development of an... (Comparative Study)
Comparative Study
BACKGROUND
Microemulsions drug delivery systems (MDDS) have been known to increase the bioavailability of hydrophobic drugs. The main challenge of the MDDS is the development of an effective and safe system for drug carriage and delivery. Biosurfactants are preferred surface-active molecules because of their lower toxicity and safe characteristics when compared to synthetic surfactants. Glycolipid and lipopeptide are the most common biosurfactants that were tested for MDDS. The main goal of the present systematic review was to estimate the available evidence on the role of biosurfactant in the development of MDDS.
SEARCH STRATEGY
Literature searches involved the main scientific databases and were focused on the period from 2005 until 2017. The Search filter composed of two items: "Biosurfactant" and/or "Microemulsion."
INCLUSION CRITERIA
Twenty-four studies evaluating the use of biosurfactant in MDDS were eligible for inclusion. Among these 14 were related to the use of glycolipid biosurfactants in the MDDS formulations, while four reported using lipopeptide biosurfactants and six other related review articles.
RESULTS
According to the output study parameters, biosurfactants acted as active stabilizers, hydrophilic or hydrophobic linkers and safety carriers in MDDS, and among them glycolipid biosurfactants had the most application in MDDS formulations.
CONCLUSION
Synthetic surfactants could be replaced by biosurfactants as an effective bio-source for MDDS due to their excellent self-assembling and emulsifying activity properties.
Topics: Drug Carriers; Drug Delivery Systems; Emulsions; Glycolipids; Humans; Hydrophobic and Hydrophilic Interactions; Lipopeptides; Pharmaceutical Preparations; Surface-Active Agents
PubMed: 32103896
DOI: 10.2147/DDDT.S232325 -
Clinical Nutrition (Edinburgh, Scotland) Mar 2021Patients who have chronic intestinal failure require home parenteral nutrition (HPN) support. Intravenous lipid emulsions (IVLEs) are a vital part of HPN. The...
Influence of different intravenous lipid emulsions on fatty acid status and laboratory and clinical outcomes in adult patients receiving home parenteral nutrition: A systematic review.
BACKGROUND & AIMS
Patients who have chronic intestinal failure require home parenteral nutrition (HPN) support. Intravenous lipid emulsions (IVLEs) are a vital part of HPN. The conventional IVLE is based on pure soybean oil, which contains a high concentration of omega-6 fatty acids. Alternative IVLEs are commercially available. These contain various oil blends and have different fatty acid compositions from soybean oil that could provide benefit to patients on HPN. The aim of this systematic review is to assess the effects of different IVLEs in adult patients requiring HPN.
METHODS
A systematic literature search was conducted up to October 2019 using relevant search terms in the Medline, EMBASE and CINAHL databases. Only randomised controlled trials (RCTs) in adults on HPN that compared two or more IVLEs were included. Data were extracted and the Cochrane Collaboration's tool for assessing risk of bias was used.
RESULTS
Six articles were identified for inclusion in this systematic review. Studies differed according to sample size, duration and the IVLEs compared. Four studies found no increased risk of adverse effects related to the different IVLEs, whilst one study found a higher frequency of serious adverse events with soybean oil. One study found higher serum α-tocopherol with the blend of soybean oil, medium chain triglycerides, olive oil and fish oil. Inflammatory markers were not affected by different IVLEs in three studies. Differences in liver function tests were minimal, but one study found slight abnormalities in patients receiving soybean oil. IVLEs containing olive oil or fish oil modified the blood fatty acid profile. No studies reported essential fatty acid deficiency.
CONCLUSIONS
There may be benefits of using alternative IVLEs to soybean oil-based emulsions in adults requiring HPN, although there is currently insufficient evidence to determine superiority of one formulation over another. More and larger RCTs are required in this area.
Topics: Adult; Dietary Fats; Fat Emulsions, Intravenous; Fatty Acids; Female; Fish Oils; Humans; Intestinal Diseases; Male; Middle Aged; Nutritional Status; Olive Oil; Parenteral Nutrition, Home; Randomized Controlled Trials as Topic; Soybean Oil; Treatment Outcome
PubMed: 32758383
DOI: 10.1016/j.clnu.2020.07.014 -
Medicine Feb 2020Influenza is a severe disease burden among all age groups. This study aimed to review the efficacy of inactivated influenza vaccines with MF59 adjuvant and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Influenza is a severe disease burden among all age groups. This study aimed to review the efficacy of inactivated influenza vaccines with MF59 adjuvant and non-adjuvanted inactivated influenza vaccines among all age groups against specific influenza vaccine strains.
METHODS
Literature search of PubMed, Embase, Medline, OVID, and Cochrane Library Trials (CENTRAL) was implemented up to March 1, 2019. Homogeneity qualified studies were included forData were extracted such as study country location, demographic characteristics, and measure outcomes, and were analyzed by a random effect model and sensitivity analyses to identify heterogeneity. Risk of bias was evaluated using the Cochrane Risk of Bias Tool.
RESULTS
We retrieved 1,021 publications and selected 31 studies for full review, including 17 trials for meta-analysis and 6 trials for qualitative synthesis. MF59-adjuvanted influenza vaccines demonstrated better immunogenicity against specific vaccine virus strains compared to non-adjuvanted influenza vaccine both in healthy adult group (RR = 2.10; 95% CI: 1.28-3.44) and the healthy aged (RR = 1.26; 95% CI: 1.10-1.44).
CONCLUSION
The quality of evidence is moderate to high for seroconversion and seroprotection rates of influenza vaccine. MF59-adjuvanted influenza vaccines are superior to non-adjuvanted influenza vaccines to enhance immune responses of vaccination in healthy adults and older adults, and could be considered for routine use especially the monovalent prepandemic influenza vaccines.
Topics: Adjuvants, Immunologic; Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Child; Female; Humans; Immunogenicity, Vaccine; Influenza Vaccines; Influenza, Human; Male; Middle Aged; Polysorbates; Randomized Controlled Trials as Topic; Seroconversion; Squalene; Vaccines, Inactivated; Young Adult
PubMed: 32049815
DOI: 10.1097/MD.0000000000019095 -
Clinical Toxicology (Philadelphia, Pa.) Oct 2021Poisoning may lead to respiratory failure, shock, cardiac arrest, or death. Extracorporeal membrane oxygenation (ECMO) may be used to provide circulatory support, termed...
CONTEXT
Poisoning may lead to respiratory failure, shock, cardiac arrest, or death. Extracorporeal membrane oxygenation (ECMO) may be used to provide circulatory support, termed venoarterial (VA) ECMO; or respiratory support termed venovenous (VV) ECMO. The clinical utility of ECMO in poisoned patients remains unclear and guidelines on its use in this setting are lacking.
OBJECTIVES
To perform a literature search and narrative review on the use of ECMO in poisonings. Additionally, to provide recommendations on the use of ECMO in poisonings from physicians with expertise in ECMO, medical toxicology, critical care, and emergency medicine.
METHODS
A literature search in Ovid MEDLINE from 1946 to October 14, 2020, was performed to identify relevant articles with a strategy utilizing both MeSH terms and adjacency searching that encompassed both extracorporeal life support/ECMO/Membrane Oxygenation concepts and chemically-induced disorders/toxicity/poisoning concepts, which identified 318 unique records. Twelve additional manuscripts were identified by the authors for a total of 330 articles for screening, of which 156 were included for this report.
NARRATIVE LITERATURE REVIEW
The use of ECMO in poisoned patients is significantly increasing over time. Available retrospective data suggest that patients receiving VA ECMO for refractory shock or cardiac arrest due to poisoning have lower mortality as compared to those who receive VA ECMO for non-poisoning-related indications. Poisoned patients treated with ECMO have reduced mortality as compared to those treated without ECMO with similar severity of illness and after adjusted analyses, regardless of the type of ingestion. This is especially evident for poisoned patients with refractory cardiac arrest placed on VA ECMO (termed extracorporeal cardiopulmonary resuscitation [ECPR]).
INDICATIONS
We suggest VA ECMO be considered for poisoned patients with refractory cardiogenic shock (continued shock with myocardial dysfunction despite fluid resuscitation, vasoactive support, and indicated toxicologic therapies such as glucagon, intravenous lipid emulsion, hyperinsulinemia euglycemia therapy, or others), and strongly considered for patients with cardiac arrest in institutions which are structured to deliver effective ECPR. VV ECMO should be considered in poisoned patients with ARDS or severe respiratory failure according to traditional indications for ECMO in this setting.
CONTRAINDICATIONS
Patients with pre-existing comorbidities with low expected survival or recovery. Relative contraindications vary based on each center's experience but often include: severe brain injury; advanced age; unrepaired aortic dissection or severe aortic regurgitation in VA ECMO; irreversible organ injury; contraindication to systemic anticoagulation, such as severe hemorrhage.
CONCLUSIONS
ECMO may provide hemodynamic or respiratory support to poisoned patients while they recover from the toxic exposure and metabolize or eliminate the toxic agent. Available literature suggests a potential benefit for ECMO use in selected poisoned patients with refractory shock, cardiac arrest, or respiratory failure. Future studies may help to further our understanding of the use and complications of ECMO in poisoned patients.
Topics: Cardiovascular System; Extracorporeal Membrane Oxygenation; Hemodynamics; Humans; Lung; Poisoning; Recovery of Function; Respiration; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 34396873
DOI: 10.1080/15563650.2021.1945082