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Topical Host-Modulating Therapy for Periodontal Regeneration: A Systematic Review and Meta-Analysis.Tissue Engineering. Part B, Reviews Dec 2019Over the past decades, locally delivered host-modulating pharmacological agents have been extensively investigated to treat periodontitis. Although a small category of... (Meta-Analysis)
Meta-Analysis
Over the past decades, locally delivered host-modulating pharmacological agents have been extensively investigated to treat periodontitis. Although a small category of agents has been tested in clinical trials, most of them were reported in the animal experiments. This systematic review evaluates the efficacy of local application of currently available host-modulating agents, with or without mechanical removal of plaque, in animal models with periodontitis or periodontal defect. PubMed and Embase were searched on February 11, 2019. The inclusion criteria were as follows: (1) experiments were performed in healthy animals (all ages, sexes, and species) with periodontitis, and (2) outcome data for the local application of host-modulating approaches were presented for bone quantity, bone loss, and attachment loss and compared with a vehicle control group. Study characteristics and outcome data were extracted and internal validity was assessed. The efficacy of host-modulating agents was analyzed in a meta-analysis. A standardized mean difference (SMD) and its 95% confidence intervals for each individual comparison were calculated to estimate the overall effect. Subgroup analyses were conducted on animal species and different types of agents. Forty-eight articles were included in the review, of which 42 were included in meta-analysis on bone quantity, bone loss, and attachment loss. The results showed that host-modulating therapy significantly increased bone formation (SMD: 2.200 [1.560-2.840], = 24), and decreased bone loss (SMD: -1.659 [-1.969 to -1.348], = 51) and attachment loss (SMD: -1.572 [-2.211 to -0.933], = 17). No significant subgroup effects were identified, indicating that the effects are similar across species and drug types. The current scientific evidence supports the use of local host-modulation therapy in the treatment of periodontitis in experimental animals. Our findings seem robust for various animal models and designs included in this review, which increases our confidence of the translational value of the results to the clinical situation. Impact Statement Over the past decades, locally delivered host-modulating pharmacological agents have been extensively investigated for periodontal regeneration. Although a small category of agents has been tested in clinical trials, most of them were reported in the animal experiments. Considering the increasing amount of preclinical evidence and the need for future clinical trials, a systematic review and meta-analysis of all preclinical data was performed to determine the translational value of host-modulating drugs for human application. The results showed that host-modulating therapy significantly increased bone formation and decreased bone and attachment loss. This study contributes to researchers working on the periodontal translational research.
Topics: Administration, Topical; Animals; Bone and Bones; Humans; Periodontitis; Pharmaceutical Preparations; Regeneration
PubMed: 31595835
DOI: 10.1089/ten.TEB.2019.0184 -
Journal of Controlled Release :... Jul 2019The idea of using extracellular vesicles (EVs) for targeted drug delivery was first introduced in 2011 and has since then gained increasing attention as promising new...
The idea of using extracellular vesicles (EVs) for targeted drug delivery was first introduced in 2011 and has since then gained increasing attention as promising new candidates in the field. Targeting EVs to areas of disease can be achieved through a complex process of designing and inserting a targeting ligand to the surface of the EVs. Although this can be obtained via chemical conjugation, the most important strategy has been to transfect or modulate the EV-producing cell to endow the EVs with the desired targeting capabilities. However, since EVs are harvested from biological sources, their composition is highly heterogeneous, which makes it difficult to control the purity and quality of the resulting EV-based drug delivery vehicles. In this review, we present a detailed account of EVs in targeted drug delivery based on a systematic literature search. We discuss the potential advantages of EVs compared to synthetic lipid-based nanocarriers, and the methodological and biological limitations associated with their use as targeted drug delivery vehicles.
Topics: Animals; Drug Delivery Systems; Extracellular Vesicles; Humans; Liposomes; Tissue Distribution
PubMed: 31175896
DOI: 10.1016/j.jconrel.2019.06.006 -
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 -
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 -
The British Journal of Dermatology Sep 2021Acne is very common and can have a substantial impact on wellbeing. Guidelines suggest first-line management with topical treatments, but there is little evidence... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acne is very common and can have a substantial impact on wellbeing. Guidelines suggest first-line management with topical treatments, but there is little evidence regarding which treatments are most effective.
OBJECTIVES
To identify the most effective and best tolerated topical treatments for acne using network meta-analysis.
METHODS
CENTRAL, MEDLINE, Embase and World Health Organization Trials Registry were searched from inception to June 2020 for randomized trials that included participants with mild/moderate acne. Primary outcomes were self-reported improvement in acne, and trial withdrawal. Secondary outcomes included change in lesion counts, Investigator's Global Assessment, change in quality of life and total number of adverse events. Network meta-analysis was undertaken using a frequentist approach. Risk of bias was assessed using the Cochrane Risk of Bias Tool and confidence in evidence was assessed using CINeMA.
RESULTS
A total of 81 papers were included, reporting 40 trials with a total of 18 089 participants. Patient Global Assessment of Improvement was reported in 11 trials. Based on the pooled network estimates, compared with vehicle, benzoyl peroxide (BPO) was effective (35% vs. 26%) for improving self-reported acne. The combinations of BPO with adapalene (54% vs. 35%) or with clindamycin (49% vs. 35%) were ranked more effective than BPO alone. The withdrawal of participants from the trial was reported in 35 trials. The number of patients withdrawing owing to adverse events was low for all treatments. Rates of withdrawal were slightly higher for BPO with adapalene (2·5%) or clindamycin (2·7%) than BPO (1·6%) or adapalene alone (1·0%). Overall confidence in the evidence was low.
CONCLUSIONS
Adapalene in combination with BPO may be the most effective treatment for acne but with a slightly higher incidence of withdrawal than monotherapy. Inconsistent reporting of trial results precluded firmer conclusions.
Topics: Acne Vulgaris; Adapalene; Benzoyl Peroxide; Dermatologic Agents; Drug Combinations; Gels; Humans; Network Meta-Analysis; Quality of Life; Treatment Outcome
PubMed: 33825196
DOI: 10.1111/bjd.20080 -
Nanomaterials (Basel, Switzerland) Sep 2021Nano-hydroxyapatite (nHA) has been widely used as an orthopedic biomaterial and vehicle for drug delivery owing to its chemical and structural similarity to bone... (Review)
Review
Nano-hydroxyapatite (nHA) has been widely used as an orthopedic biomaterial and vehicle for drug delivery owing to its chemical and structural similarity to bone minerals. Several studies have demonstrated that nHA based biomaterials have a potential effect for bone regeneration with very minimal to no toxicity or inflammatory response. This systematic review aims to provide an appraisal of the effectiveness of nHA as a delivery system for bone regeneration and whether the conjugation of proteins, antibiotics, or other bioactive molecules to the nHA further enhances osteogenesis in vivo. Out of 282 articles obtained from the literature search, only 14 articles met the inclusion criteria for this review. These studies showed that nHA was able to induce bone regeneration in various animal models with large or critical-sized bone defects, open fracture, or methicillin-resistant (MRSA)-induced osteomyelitis. The conjugations of drugs or bioactive molecules such as bone-morphogenetic protein-2 (BMP-2), vancomycin, calcitriol, dexamethasone, and cisplatin were able to enhance the osteogenic property of nHA. Thus, nHA is a promising delivery system for a variety of compounds in promoting bone regeneration in vivo.
PubMed: 34685010
DOI: 10.3390/nano11102569 -
American Journal of Ophthalmology Jan 2024To summarize key findings from a Cochrane review of the benefits and safety of antibiotic therapy compared with placebo (or vehicle) for acute bacterial conjunctivitis. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To summarize key findings from a Cochrane review of the benefits and safety of antibiotic therapy compared with placebo (or vehicle) for acute bacterial conjunctivitis.
DESIGN
Systematic review and meta-analysis.
METHODS
We included placebo-controlled randomized controlled trials (RCTs) that compared topical antibiotics with placebo. We followed Cochrane methods for trial selection, data extraction, risk of bias assessment, and evidence synthesis.
RESULTS
Twenty-one RCTs involving 8805 participants with acute bacterial conjunctivitis were included. Fifteen (71%) RCTs examined fluoroquinolone (FQ) drops, 3 tested macrolides, alone or in combination with steroids, and another 3 compared other non-FQ antibiotics. Intention-to-treat estimates suggested that compared with placebo, antibiotics may increase clinical recovery by 26% (risk ratio [RR]: 1.26; 95% confidence interval [CI]: 1.09-1.46) at the end of therapy (5 RCTs, 1474 participants). Modified intention-to-treat estimates, in which only participants with laboratory-confirmed bacterial conjunctivitis were analyzed, indicated that antibiotics were associated with 53% higher likelihood of microbiological cure as compared with placebo (RR: 1.53; 95% CI: 1.34-1.74; 10 RCTs, 2827 participants). Non-FQs (RR: 4.05; 95% CI: 1.36-12.00), but not FQs (RR: 0.70; 95% CI: 0.54-0.90), were likely to increase treatment-associated ocular complications such as eye pain, discomfort, and allergic reactions; the certainty of level of evidence was very low.
CONCLUSIONS
Moderate level certainty of evidence suggested that antibiotics may increase the likelihood of clinical recovery and microbiological clearance compared with placebo. Very low-level certainty of evidence suggested that antibiotics may be associated with potential harm in patients with acute bacterial conjunctivitis, but the potential risk of bias from study design, inconsistency in outcome measurement, and reporting limit the evidence to very low certainty.
Topics: Humans; Anti-Bacterial Agents; Conjunctivitis, Bacterial
PubMed: 37482371
DOI: 10.1016/j.ajo.2023.06.027 -
Mucoadhesive delivery systems for oral candidiasis treatment: A systematic review and meta-analysis.Oral Diseases Mar 2024This systematic review and meta-analysis aimed to evaluate the clinical and mycological effectiveness of mucoadhesives as vehicles for drugs or natural products in the... (Review)
Review
OBJECTIVES
This systematic review and meta-analysis aimed to evaluate the clinical and mycological effectiveness of mucoadhesives as vehicles for drugs or natural products in the treatment of oral candidiasis.
MATERIALS AND METHODS
The search for articles was carried out in the Medline/PubMed, SCOPUS, EMBASE, Web of Science, Cochrane Library, and SciELO databases before August 2023. We selected the studies, extracted the data, evaluated the study quality, graded the evidence, performed the risk of bias, and carried out meta-analysis.
RESULTS
A total of 389 potentially relevant articles were identified, and 11 studies (1869 participants) met the inclusion criteria of the systematic review. The overall risk of bias was considered low. The most common presentation of mucoadhesives was tablets, with miconazole being the most frequently drug used in the delivery system. Mucoadhesives demonstrated comparable efficacy with topical or systemic antifungal agents, with no significant differences between treatments in terms of clinical (RR = 0.907; 95CI = 0.3-1.297; p = 0.591; I = 64.648) or mycological (RR = 0.95; 95CI = 0.667-1.360; p = 0.789; I = 73.271) efficacy.
CONCLUSIONS
Mucoadhesives may be a suitable alternative to conventional treatments, with the advantage of reducing the frequency of application by up to 5 times and the daily dosage by up to 20 times.
PubMed: 38523365
DOI: 10.1111/odi.14928 -
Neuropsychopharmacology : Official... Mar 2022We searched PubMed for primary research quantifying drug modification of light-induced circadian phase-shifting in rodents. This search, conducted for work published...
We searched PubMed for primary research quantifying drug modification of light-induced circadian phase-shifting in rodents. This search, conducted for work published between 1960 and 2018, yielded a total of 146 papers reporting results from 901 studies. Relevant articles were those with any extractable data on phase resetting in wildtype (non-trait selected) rodents administered a drug, alongside a vehicle/control group, near or at the time of exposure. Most circadian pharmacology experiments were done using drugs thought to act directly on either the brain's central pacemaker, the suprachiasmatic nucleus (SCN), the SCN's primary relay, the retinohypothalamic tract, secondary pathways originating from the medial/dorsal raphe nuclei and intergeniculate leaflet, or the brain's sleep-arousal centers. While the neurotransmitter systems underlying these circuits were of particular interest, including those involving glutamate, gamma-aminobutyric acid, serotonin, and acetylcholine, other signaling modalities have also been assessed, including agonists and antagonists of receptors linked to dopamine, histamine, endocannabinoids, adenosine, opioids, and second-messenger pathways downstream of glutamate receptor activation. In an effort to identify drugs that unduly influence circadian responses to light, we quantified the net effects of each drug class by ratioing the size of the phase-shift observed after administration to that observed with vehicle in a given experiment. This allowed us to organize data across the literature, compare the relative efficacy of one mechanism versus another, and clarify which drugs might best suppress or potentiate phase resetting. Aggregation of the available data in this manner suggested that several candidates might be clinically relevant as auxiliary treatments to suppress ectopic light responses during shiftwork or amplify the circadian effects of timed bright light therapy. Future empirical research will be necessary to validate these possibilities.
Topics: Circadian Rhythm; Pharmaceutical Preparations; S Phase; Serotonin; Suprachiasmatic Nucleus
PubMed: 34961774
DOI: 10.1038/s41386-021-01251-8 -
Expert Review of Clinical Pharmacology Dec 2022To investigate the clinical efficacy and safety of topical difamilast in mild-to-moderate atopic dermatitis (AD). (Meta-Analysis)
Meta-Analysis
Clinical efficacy and safety of topical difamilast in the treatment of patients with atopic dermatitis: a systematic review and meta-analysis of randomized controlled trials.
OBJECTIVE
To investigate the clinical efficacy and safety of topical difamilast in mild-to-moderate atopic dermatitis (AD).
METHODS
Only randomized controlled trials (RCTs) that compared topical difamilast with vehicle treatment for patients with AD were included. PubMed, Web of Science, Ovid Medline, Cochrane Library, ClinicalTrials.gov and JapicCTI were searched to 10 April 2022.
RESULTS
Five studies enrolling a total of 1009 patients with mild-to-moderate AD were identified. Compared with the topical vehicle, topical difamilast was associated with a significantly higher success rate according to the Investigator's Global Assessment score at week 4 (relative risk, 2.82; 95% confidence interval [CI]: 2.11-3.77). Compared with the vehicle, difamilast was associated with a significant decrease in day 28 eczema area and severity index scores (mean difference [MD], -4.10; 95% CI: -5.32 to -2.87), verbal rating scale scores (MD, -0.51; 95% CI: -0.71 to -0.32), visual analog scale scores (MD, -12.15; 95% CI: -19.70 to -4.61), patient-oriented eczema measure values (MD, -3.99; 95% CI: -4.91 to -3.07), and total affected body surface area (MD, -6.48; 95% CI: -8.09 to -4.87). No difference in treatment-related adverse events was identified.
CONCLUSIONS
This meta-analysis suggests that topical difamilast is an effective and safe treatment for mild-to-moderate AD.
Topics: Humans; Dermatitis, Atopic; Randomized Controlled Trials as Topic; Treatment Outcome; Eczema; Double-Blind Method; Severity of Illness Index
PubMed: 36210241
DOI: 10.1080/17512433.2022.2134114