-
Journal of Nanobiotechnology Jan 2024Exosomes are nanoscale extracellular vesicles secreted by cells and enclosed by a lipid bilayer membrane containing various biologically active cargoes such as proteins,... (Review)
Review
Exosomes are nanoscale extracellular vesicles secreted by cells and enclosed by a lipid bilayer membrane containing various biologically active cargoes such as proteins, lipids, and nucleic acids. Engineered exosomes generated through genetic modification of parent cells show promise as drug delivery vehicles, and they have been demonstrated to have great therapeutic potential for treating cancer, cardiovascular, neurological, and immune diseases, but systematic knowledge is lacking regarding optimization of drug loading and assessment of delivery efficacy. This review summarizes current approaches for engineering exosomes and evaluating their drug delivery effects, and current techniques for assessing exosome drug loading and release kinetics, cell targeting, biodistribution, pharmacokinetics, and therapeutic outcomes are critically examined. Additionally, this review synthesizes the latest applications of exosome engineering and drug delivery in clinical translation. The knowledge compiled in this review provides a framework for the rational design and rigorous assessment of exosomes as therapeutics. Continued advancement of robust characterization methods and reporting standards will accelerate the development of exosome engineering technologies and pave the way for clinical studies.
Topics: Humans; Exosomes; Tissue Distribution; Drug Delivery Systems; Extracellular Vesicles; Neoplasms; Pharmaceutical Preparations
PubMed: 38172932
DOI: 10.1186/s12951-023-02259-6 -
World Neurosurgery Apr 2024Traumatic spinal cord injury (TSCI) is a debilitating neurological condition with significant long-term consequences on the mental health and well-being of affected... (Review)
Review
BACKGROUND
Traumatic spinal cord injury (TSCI) is a debilitating neurological condition with significant long-term consequences on the mental health and well-being of affected individuals. We aimed to investigate anxiety and depression in individuals with pediatric-onset TSCI.
METHODS
PubMed, Scopus, and Web of Science databases were searched from inception to December 20th, 2022 following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, and studies were included according to the eligibility criteria.
RESULTS
A total of 1013 articles were screened, and 18 studies with 4234 individuals were included in the final review. Of these, 1613 individuals (38.1%) had paraplegia, whereas 1658 (39.2%) had tetraplegia. A total of 1831 participants (43.2%) had complete TSCI, whereas 1024 (24.2%) had incomplete TSCI. The most common etiology of TSCI with 1545 people (36.5%) was motor vehicle accidents. The youngest mean age at the time of injury was 5.92 ± 4.92 years, whereas the oldest was 14.6 ± 2.8 years. Patient Health Questionnaire-9 was the most common psychological assessment used in 9 studies (50.0%). Various risk factors, including pain in 4 studies (22.2%), reduced sleep quality, reduced functional independence, illicit drug use, incomplete injury, hospitalization, reduced quality of life, and duration of injury in 2 (11.1%) studies, each, were associated with elevated anxiety and depression.
CONCLUSIONS
Different biopsychosocial risk factors contribute to elevated rates of anxiety and depression among individuals with pediatric-onset TSCI. Individuals at risk of developing anxiety and depression should be identified, and targeted support should be provided. Future large-scale studies with long-term follow-up are required to validate and extend these findings.
Topics: Child; Humans; Infant; Child, Preschool; Depression; Quality of Life; Spinal Cord Injuries; Paraplegia; Anxiety
PubMed: 38143027
DOI: 10.1016/j.wneu.2023.12.092 -
Contact Lens & Anterior Eye : the... Feb 2024To comprehensively review the efficacy and safety of OC-01 varenicline nasal spray versus vehicle nasal spray (VNS) in the treatment in dry eye disease (DED). (Review)
Review
PURPOSE
To comprehensively review the efficacy and safety of OC-01 varenicline nasal spray versus vehicle nasal spray (VNS) in the treatment in dry eye disease (DED).
METHODS
A systematic review that included full-length randomized controlled studies (RCTs), as well as post hoc analyses of RCTs reporting new findings on OC-01 VNS treatment in three databases, PubMed, Scopus and Web of Science, was performed according to the PRISMA statement. The search period included studies published between December 2021 and September 2023. The Cochrane risk of bias tool was used to analyze the quality of the studies selected.
RESULTS
A total of 8 studies were included in this systematic review. OC-01 VNS treatment achieved higher improvement than vehicle in all reported variables. The mean differences between both groups were in favor of OC-01 VNS treatment and were as follow: eye dryness score base on a visual analogue scale (EDS-VAS) of -7.5 ± 2.2 points [-11.6 to -5.6], Schirmer test (ST) with anesthesia of 6.6 ± 2.3 mm [4.9 to 11.8] and total corneal fluorescein staining (tCFS) of -1.2 ± 0.01 points [-1.2 to -1.1]. Similar improvements were reported with OC-01 VNS 0.03 mg and 0.06 mg. Adverse events (AEs) were 15.5 ± 19.4 % [-13 to 80.5] higher in the OC-01 VNS group with an overall adherence > 93 %.
CONCLUSIONS
OC-01 VNS improves dry eye symptoms and signs with a satisfactory tolerability. Therefore, OC-01 VNS seems to be a safe and effective treatment that could be recommended in patients with DED. This new treatment could be particularly useful in those patients who have difficulties with the administration of traditional topical therapies.
Topics: Humans; Dry Eye Syndromes; Fluorescein; Nasal Sprays; Tears; Varenicline
PubMed: 38065797
DOI: 10.1016/j.clae.2023.102097 -
Dermatology (Basel, Switzerland) 2024Psoriasis is a chronic immune-mediated skin disease. Several clinical trials have studied some topical drugs aiming at new therapeutic targets. However, the comparative... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Psoriasis is a chronic immune-mediated skin disease. Several clinical trials have studied some topical drugs aiming at new therapeutic targets. However, the comparative efficacy and safety of different concentrations and frequencies of newer topical drugs for psoriasis remain unclear. The aim of our study is to assess the comparative efficacy and safety of some newer topical treatments in patients with psoriasis.
METHODS
A systematic review and network meta-analysis (NMA) was conducted using eligible randomized controlled trials (RCTs). Treatments included topical therapeutic aryl hydrocarbon receptor (AhR)-modulating agent (TAMA), topical phosphodiesterase type 4 (PDE-4) inhibitors, and topical janus kinase-signal transducer and activator of transcription (JAK-STAT) inhibitors. The primary efficacy assessment criterion was the proportion of patients' achieving Physician's Global Assessment 0/1 (PGA response). Secondary criterion was ≥75% reductions in the Psoriasis Area and Severity Index (PASI75). Adverse events (AEs) to represent the safety were also summarized.
RESULTS
Among 6 including newer topical drugs, odds of achieving both PGA response and PASI75 were higher with all regimens of TAMA and roflumilast cream versus vehicle. In terms of safety outcomes, odds of AEs were also higher with all regimens of TAMA. There were no statistically significant differences between topical JAK-STAT inhibitors and vehicle for any outcome, except ruxolitinib ointment 1% once daily (QD).
CONCLUSION
TAMA had a good therapeutic effect on plaque psoriasis but a relatively low treatment safety. Roflumilast cream had both promising efficacy and higher safety.
Topics: Humans; Network Meta-Analysis; Aminopyridines; Benzamides; Psoriasis; Chronic Disease; Treatment Outcome; Cyclopropanes
PubMed: 37939679
DOI: 10.1159/000535056 -
JAMA Nov 2023Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality. (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality.
OBJECTIVE
To compare efficacy and comparative efficacy of therapies for alcohol use disorder.
DATA SOURCES
PubMed, the Cochrane Library, the Cochrane Central Trials Registry, PsycINFO, CINAHL, and EMBASE were searched from November 2012 to September 9, 2022 Literature was subsequently systematically monitored to identify relevant articles up to August 14, 2023, and the PubMed search was updated on August 14, 2023.
STUDY SELECTION
For efficacy outcomes, randomized clinical trials of at least 12 weeks' duration were included. For adverse effects, randomized clinical trials and prospective cohort studies that compared drug therapies and reported health outcomes or harms were included.
DATA EXTRACTION AND SYNTHESIS
Two reviewers evaluated each study, assessed risk of bias, and graded strength of evidence. Meta-analyses used random-effects models. Numbers needed to treat were calculated for medications with at least moderate strength of evidence for benefit.
MAIN OUTCOMES AND MEASURES
The primary outcome was alcohol consumption. Secondary outcomes were motor vehicle crashes, injuries, quality of life, function, mortality, and harms.
RESULTS
Data from 118 clinical trials and 20 976 participants were included. The numbers needed to treat to prevent 1 person from returning to any drinking were 11 (95% CI, 1-32) for acamprosate and 18 (95% CI, 4-32) for oral naltrexone at a dose of 50 mg/d. Compared with placebo, oral naltrexone (50 mg/d) was associated with lower rates of return to heavy drinking, with a number needed to treat of 11 (95% CI, 5-41). Injectable naltrexone was associated with fewer drinking days over the 30-day treatment period (weighted mean difference, -4.99 days; 95% CI, -9.49 to -0.49 days) Adverse effects included higher gastrointestinal distress for acamprosate (diarrhea: risk ratio, 1.58; 95% CI, 1.27-1.97) and naltrexone (nausea: risk ratio, 1.73; 95% CI, 1.51-1.98; vomiting: risk ratio, 1.53; 95% CI, 1.23-1.91) compared with placebo.
CONCLUSIONS AND RELEVANCE
In conjunction with psychosocial interventions, these findings support the use of oral naltrexone at 50 mg/d and acamprosate as first-line pharmacotherapies for alcohol use disorder.
Topics: Humans; Acamprosate; Alcohol Drinking; Alcoholism; Drug-Related Side Effects and Adverse Reactions; Naltrexone; Prospective Studies; Quality of Life; United States; Alcohol Deterrents; Psychosocial Intervention
PubMed: 37934220
DOI: 10.1001/jama.2023.19761 -
Cyclodextrin inclusion complexes improving antibacterial drug profiles: an update systematic review.Future Microbiology Dec 2023The study aimed to review experimental models using cyclodextrins to improve antibacterial drugs' physicochemical characteristics and biological activities. The...
The study aimed to review experimental models using cyclodextrins to improve antibacterial drugs' physicochemical characteristics and biological activities. The following terms and their combinations were used: cyclodextrins and antibacterial agents in title or abstract, and the total study search was conducted over a period up to October 2022. The review was carried out using PubMed, Scopus and Embase databases. A total of 1580 studies were identified, of which 27 articles were selected for discussion in this review. The biological results revealed that the antibacterial effect of the inclusion complexes was extensively improved. Cyclodextrins can enhance the therapeutic effects of antibiotics already existing on the market, natural products and synthetic molecules. Overall, CDs as drug-delivery vehicles have been shown to improve antibiotics solubility, stability, and bioavailability, leading to enhanced antibacterial activity.
Topics: Anti-Bacterial Agents; Cyclodextrins; Solubility
PubMed: 37910070
DOI: 10.2217/fmb-2023-0124 -
Pediatric Dermatology 2023Molluscum contagiosum (MC) is a contagious infection that, although benign, can become an aesthetic burden and lead to other opportunistic infections, secondary... (Meta-Analysis)
Meta-Analysis
Safety and efficacy of topical nitric oxide-releasing berdazimer gel for molluscum contagiosum clearance: A systematic review and meta-analysis of randomized controlled trials.
Molluscum contagiosum (MC) is a contagious infection that, although benign, can become an aesthetic burden and lead to other opportunistic infections, secondary dermatitis, and self-isolation. Currently, several treatment options are available for MC, including the newly investigated nitric oxide-releasing berdazimer gel, leading this review to evaluate randomized controlled trials (RCT) comparing berdazimer gel with a vehicle for treating MC. The meta-analysis included three reports and four RCT involving 1854 patients, with 1106 (59.6%) randomized to receive berdazimer. Our findings suggest that berdazimer is effective in the management of MC lesions, but the increased clearance of lesions and reduction of scarring must be weighed against the potential for topical adverse effects, particularly when considering the use of this therapy in pediatric patients.
Topics: Child; Humans; Molluscum Contagiosum; Nitric Oxide; Treatment Outcome; Randomized Controlled Trials as Topic; Gels
PubMed: 37721050
DOI: 10.1111/pde.15419 -
International Journal of Biological... Dec 2023Gold nanoparticles have been broadly investigated as cancer diagnostic and therapeutic agents. Gold nanoparticles are a favorable drug delivery vehicle with their unique...
Gold nanoparticles have been broadly investigated as cancer diagnostic and therapeutic agents. Gold nanoparticles are a favorable drug delivery vehicle with their unique subcellular size and good biocompatibility. Chitosan, agarose, fucoidan, porphyran, carrageenan, ulvan and alginate are all examples of biologically active macromolecules. Since they are biocompatible, biodegradable, and irritant-free, they find extensive application in biomedical and macromolecules. The versatility of these compounds is enhanced because they are amenable to modification by functional groups like sulfation, acetylation, and carboxylation. In an eco-friendly preparation process, the biocompatibility and targeting of GNPs can be improved by functionalizing them with polysaccharides. This article provides an update on using carbohydrate-based GNPs in liver cancer treatment, imaging, and drug administration. Selective surface modification of several carbohydrate types and further biological uses of GNPs are focused on.
Topics: Humans; Gold; Polymers; Metal Nanoparticles; Nanoparticles; Carbohydrates; Liver Neoplasms
PubMed: 37714232
DOI: 10.1016/j.ijbiomac.2023.126889 -
Drug Delivery and Translational Research Feb 2024Extracellular vesicles (EVs), which are nanoparticles that are actively released by cells, contain a variety of biologically active substances, serve as significant...
Extracellular vesicles (EVs), which are nanoparticles that are actively released by cells, contain a variety of biologically active substances, serve as significant mediators of intercellular communication, and participate in many processes, in health and pathologically. Compared with traditional nanodrug delivery systems (NDDSs), EVs have unique advantages due to their natural physiological properties, such as their biocompatibility, stability, ability to cross barriers, and inherent homing properties. A growing number of studies have reported that EVs deliver therapeutic proteins, small-molecule drugs, siRNAs, miRNAs, therapeutic proteins, and nanomaterials for targeted therapy in various diseases. However, due to the lack of standardized techniques for isolating, quantifying, and characterizing EVs; lower-than-anticipated drug loading efficiency; insufficient clinical production; and potential safety concerns, the practical application of EVs still faces many challenges. Here, we systematically review the current commonly used methods for isolating EVs, summarize the types and methods of loading therapeutic drugs into EVs, and discuss the latest progress in applying EVs as NDDs. Finally, we present the challenges that hinder the clinical application of EVs.
Topics: Extracellular Vesicles; Nanoparticle Drug Delivery System; Nanoparticles; RNA, Small Interfering; Humans
PubMed: 37581742
DOI: 10.1007/s13346-023-01411-x -
Journal of Cosmetic Dermatology Oct 2023Topical azelaic acid (AA) is indicated for acne and rosacea, but there is some evidence for its use for other dermatological conditions. (Review)
Review
BACKGROUND
Topical azelaic acid (AA) is indicated for acne and rosacea, but there is some evidence for its use for other dermatological conditions.
AIMS
To assess the effectiveness and safety of topical AA for acne vulgaris, rosacea, hyperpigmentation/melasma, and skin aging.
METHODS
RCTs of at least 6 weeks' treatment duration were eligible for inclusion. Databases including MEDLINE, Embase, CINAHL, and ClinicalTrials.gov were searched up to December 2022. Two reviewers were involved in all stages of the systematic review process.
RESULTS
Forty-three RCTs met the inclusion criteria. Meta-analyses within 20 rosacea studies demonstrated that erythema severity, inflammatory lesion counts, overall improvement, and treatment success (achieving skin clarity) were significantly improved with AA compared with vehicle after 12 weeks. AA was more effective than metronidazole 0.75% for improved erythema severity, overall improvement, and inflammatory lesion counts. Sixteen acne studies suggest that AA is more effective than vehicle for improving global assessments and reducing acne severity. AA 20% also significantly reduced more lesions than erythromycin gel. Within seven melasma studies, AA 20% was significantly better than vehicle for both severity and global improvement. AA 20% demonstrated significantly better results compared with hydroquinone 2% for global improvement. Very few significant differences between AA and comparators were observed for commonly reported adverse events. No eligible RCTs were found that evaluated skin aging.
CONCLUSIONS
AA is more effective than vehicle for rosacea, acne and melasma. Comparisons between AA and other treatments were often equivalent. Where there is equivalence, AA may be a good option for some clinical situations. RCT evidence is needed to evaluate the effectiveness of AA on skin aging.
Topics: Humans; Skin Aging; Acne Vulgaris; Rosacea; Erythema; Treatment Outcome; Melanosis; Dermatologic Agents
PubMed: 37550898
DOI: 10.1111/jocd.15923