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International Journal of Molecular... Oct 2023The administration of therapeutic drugs through dermal routes, such as creams and ointments, has emerged as an increasingly popular alternative to traditional delivery...
The administration of therapeutic drugs through dermal routes, such as creams and ointments, has emerged as an increasingly popular alternative to traditional delivery methods, such as tablets and injections. In the context of drug development, it is crucial to identify the optimal doses and delivery routes that ensure successful outcomes. Physiologically based pharmacokinetic (PBPK) models have been proposed to simulate drug delivery and optimize drug formulations, but the calibration of these models is challenging due to the multitude of variables involved and limited experimental data. One significant research gap that this article addresses is the need for more efficient and accurate methods for calibrating PBPK models for dermal drug delivery. This manuscript presents a novel approach and an integrated dermal drug delivery model to address this gap that leverages virtual in vitro release (IVRT) and permeation (IVPT) testing data to optimize mechanistic models. The proposed approach was demonstrated through a study involving Desoximetasone cream and ointment formulations, where the release kinetics and permeation profiles of Desoximetasone were determined experimentally, and a computational model was created to simulate the results. The experimental studies showed that, even though the cumulative permeation of Desoximetasone at the end of the permeation study was comparable, there was a significant difference seen in the lag time in the permeation of Desoximetasone between the cream and ointment. Additionally, there was a significant difference seen in the amount of Desoximetasone permeated through human cadaver skin at early time points when the cream and ointment were compared. The computational model was optimized and validated, suggesting that this approach has the potential to bridge the existing research gap by improving the accuracy and efficiency of drug development processes. The model results show a good fit between the experimental data and model predictions. During the model optimization process, it became evident that there was variability in both the permeability and the partition coefficient within the stratum corneum. This variability had a significant and noteworthy influence on the overall performance of the model, especially when it came to its capacity to differentiate between cream and ointment formulations. Leveraging virtual models significantly aids the comprehension of drug release and permeation, mitigating the demanding data requirements. The use of virtual IVRT and IVPT data can accelerate the calibration of PBPK models, streamline the selection of the appropriate doses, and optimize drug delivery. Moreover, this novel approach could potentially reduce the time and resources involved in drug development, thus making it more cost-effective and efficient.
Topics: Humans; Ointments; Desoximetasone; Skin; Skin Absorption; Computer Simulation; Administration, Cutaneous
PubMed: 37894801
DOI: 10.3390/ijms242015118 -
Phytomedicine : International Journal... Jan 2024Baimai ointment is a traditional Tibetan topical ointment, which is widely used for various diseases related to the skeletal muscular system and neurological... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Baimai ointment is a traditional Tibetan topical ointment, which is widely used for various diseases related to the skeletal muscular system and neurological rehabilitation. It has demonstrated good clinical effectiveness. However, there is currently a lack of high-quality evidence regarding the clinical effectiveness of Baimai ointment in treating lumbar disc herniation (LDH).
PURPOSE
In this study, we conducted a prospective, multicenter, double-blind, randomized controlled trial at eight hospitals in China to investigate the clinical effectiveness of Baimai ointment in the treatment of LDH.
METHODS
Participants aged 18-65 years were diagnosed as LDH and were randomly assigned to receive either Baimai ointment or placebo. The treatment duration was 2 weeks, with 1-week follow-up after treatment. The primary outcome measures included VAS and JOA score. The secondary outcome measures included Likert scale, compliance with health education and the incidence of rescue therapy. The intervention effects on these outcomes were examined by generalized estimating equations (GEE) with baseline measurement as the covariates. All statistical analysis were performed using SPSS 25.0 and Python 3.11.
RESULTS
In total, 228 participants were screened from August 25, 2021 to January 31, 2022 at 8 Grade-A tertiary hospitals in China. Finally, 194 eligible participants were randomly assigned to the Baimai ointment group and placebo group in a 1:1 ratio. At the end of 2-week treatment (14th day) and 1-week follow-up after treatment (21st day), the decrease of VAS reached 39.57% (95% CI: 34.29, 44.86) and 36.85% (95% CI: 32.04, 41.66), the decrease in JOA score reached 27.74% (95% CI: 23.05, 32.43) and 26.25 % (95% CI: 20.82, 31.69) in Baimai ointment group. A significant group-by-time interaction indicated a difference for VAS between intervention over time (χ = 26.81, p = 0.020), but JOA score and Likert scale did not reach statistical significance. The adjusted net difference of VAS was statistically significant from 10th day of treatment (p < 0.05). After 2-week treatment, the relief rate of VAS was 30.85% (21.95, 41.34) in Baimai ointment group and 22.73% (14.75, 33.13) in placebo group (χ = 1.53, p = 0.217). It demonstrated Baimai ointment in improving VAS and JOA score was valuable from a clinical view by measuring MCID. Moreover, the Likert scale, the incidence of rescue therapy and compliance with health education did not reach statistical significance. There was no evidence showing that Baimai ointment could cause serious adverse reactions in treating patients with LDH.
CONCLUSION
Baimai ointment demonstrated significantly higher rates of symptom relief compared to the placebo for LDH patients, particularly in terms of relieving pain. Moreover, further high-quality randomized controlled trials were necessary to confirm these positive results. The study protocol is registered with the Clinical Trials Registry (registration number: ISRCTN11912818).
Topics: Humans; Double-Blind Method; Drugs, Chinese Herbal; Intervertebral Disc Displacement; Prospective Studies; Treatment Outcome; Adolescent; Young Adult; Adult; Middle Aged; Aged
PubMed: 37922792
DOI: 10.1016/j.phymed.2023.155138 -
Clinical Case Reports Oct 2023Radiation dermatitis is one of the most common adverse effects that occur in patients treated with radiation therapy. It is usually limited to the irradiated area....
Radiation dermatitis is one of the most common adverse effects that occur in patients treated with radiation therapy. It is usually limited to the irradiated area. However, cases of generalized lesions have also been described in the literature. A rare but highly important cutaneous manifestation can be erythema multiforme-like lesions localized all over the patient's skin. A 63-year-old patient was admitted to the Department of Dermatology for disseminated erythematous lesions localized on the trunk and extremities. The patient denied taking any new medications or dietary supplements. However, he was undergoing radiotherapy treatment. On admission, the patient was in good general condition. During the stay in the department, the patient was treated orally as well as intravenously with corticosteroids, acyclovir, and a topical ointment consisting of gentamicin and betamethasone, as well as hydrocortisone and cooling ointment. After 1 month, a significant improvement in the patient's skin condition was noted. When skin lesions resembling erythema multiforme occur in patients undergoing oncological treatment, radiation therapy should be considered as a potential trigger.
PubMed: 37854261
DOI: 10.1002/ccr3.7913 -
Gels (Basel, Switzerland) Apr 2024Various controlled delivery systems (CDSs) have been developed to overcome the shortcomings of traditional drug formulations (tablets, capsules, syrups, ointments,... (Review)
Review
Various controlled delivery systems (CDSs) have been developed to overcome the shortcomings of traditional drug formulations (tablets, capsules, syrups, ointments, etc.). Among innovative CDSs, hydrogels and liposomes have shown great promise for clinical applications thanks to their cost-effectiveness, well-known chemistry and synthetic feasibility, biodegradability, biocompatibility and responsiveness to external stimuli. To date, several liposomal- and hydrogel-based products have been approved to treat cancer, as well as fungal and viral infections, hence the integration of liposomes into hydrogels has attracted increasing attention because of the benefit from both of them into a single platform, resulting in a multifunctional drug formulation, which is essential to develop efficient CDSs. This short review aims to present an updated report on the advancements of liposome-hydrogel systems for drug delivery purposes.
PubMed: 38667703
DOI: 10.3390/gels10040284 -
Pharmaceutics Oct 2023This study aimed to develop novel topical formulations based on a natural component (0.5% of Siberian pine essential oil) and to assess its wound-healing capacity...
This study aimed to develop novel topical formulations based on a natural component (0.5% of Siberian pine essential oil) and to assess its wound-healing capacity through macroscopic, histopathological, and biochemical examination. The phytochemical profile of essential oil (PSEO) and rheological analysis and safety potential of formulations were determined. The wound-healing effect was evaluated on an excision wound model in diabetic rats randomly divided into the following groups topically treated with (1) untreated, (2) 1% silver sulfadiazine, (3) ointment base, (4) gel base, (5) PSEO ointment, and (6) PSEO gel. Formulations containing PSEO were stable and safe for skin application. Three weeks of treatment with both PSEO formulations (ointment and gel) led to a significant reduction in wound size (98.14% and 96.28%, respectively) and a remarkably higher level of total hydroxyproline content (9.69 µg/mg and 7.26 µg/mg dry tissue, respectively) relative to the control group (65.97%; 1.81 µg/mg dry tissue). These findings were in correlation with histopathological results. Topically applied PSEO formulations were associated with a significant reduction in most of the measured pro-oxidants and enhanced activity of the antioxidant defense system enzymes ( < 0.05). Our findings showed that gel and ointment with PSEO demonstrated significant wound-repairing capabilities in the excision wound model.
PubMed: 37896197
DOI: 10.3390/pharmaceutics15102437 -
Journal of Clinical Medicine Jul 2023Actinic keratosis (AK) is a cutaneous lesion resulting from the proliferation of atypical epidermal keratinocytes caused by long-term exposure to ultraviolet radiation....
BACKGROUND
Actinic keratosis (AK) is a cutaneous lesion resulting from the proliferation of atypical epidermal keratinocytes caused by long-term exposure to ultraviolet radiation. AK may progress to cutaneous squamous cell carcinoma (cSCC) and therefore is often treated with topical agents such as 5-fluorouracil, diclofenac, imiquimod, and photodynamic therapy. Tirbanibulin has been approved based on two phase III trials in the USA. However, real-world evidence for tirbanibulin is absent.
METHODS
This was a single-centre study of adult patients with clinically typical, visible AK on the face or scalp treated with tirbanibulin 1% ointment. Treatment was administered as per label once daily for 5 consecutive days on the same lesions or field. Treatment outcomes were assessed 4 weeks after treatment, with additional optional assessments conducted at later time points. Efficacy was measured using the actinic keratosis area and severity index (AKASI) and digital dermoscopy.
RESULTS
A total of 33 patients were treated of whom 30 were analysed. The median AKASI score was 5.6 (1.4-11) pre-treatment and 1.2 (0-7.4) post-treatment ( < 0.0001). Complete clearance as defined by AKASI scores less than 1 was achieved in 47% ( = 14) and 57% ( = 13) at the first and second follow-up, respectively. All local reactions resolved spontaneously and without sequelae. The most common local reactions were erythema (80%, = 26) and flaking or scaling (43%, = 13).
CONCLUSIONS
Tirbanibulin 1% ointment significantly and rapidly reduced the AKASI score in a real-world setting. The complete clearance rates were in line with those observed in the two pivotal trials.
PubMed: 37510952
DOI: 10.3390/jcm12144837 -
JAMA Dermatology Feb 2024Atopic dermatitis (AD) and plaque psoriasis are inflammatory skin diseases with unmet need for effective topical treatments with few application site reactions. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Atopic dermatitis (AD) and plaque psoriasis are inflammatory skin diseases with unmet need for effective topical treatments with few application site reactions.
OBJECTIVE
To assess the efficacy and safety of the topical phosphodiesterase 4 inhibitor PF-07038124 in patients with AD and plaque psoriasis.
DESIGN, SETTING, AND PARTICIPANTS
This phase 2a, randomized, double-blind clinical trial was conducted from December 21, 2020, to August 18, 2021, at 34 sites across 4 countries. Eligible patients (aged 18-70 years) had mild to moderate AD (covering 5%-20% body surface area) or plaque psoriasis (covering 5%-15% body surface area). Data were analyzed until December 15, 2021.
INTERVENTIONS
Patients were randomized (1:1) to PF-07038124, 0.01%, topical ointment or vehicle once daily for 6 weeks.
MAIN OUTCOMES AND MEASURES
The primary end point was the percent change from baseline (CFB) in the Eczema Area and Severity Index (EASI) total score among patients with AD and in the Psoriasis Area and Severity Index (PASI) score among patients with plaque psoriasis at week 6. Safety measures included treatment-emergent adverse events, including application site reactions.
RESULTS
Overall, 104 patients were randomized (mean [SD] age, 43.0 [15.4] years; 55 [52.9%] women; 4 [3.8%] Asian, 13 [12.5%] Black, and 87 [83.7%] White), including 70 with AD (41 women [58.6%]; mean [SD] ages, 41.4 [16.6] years in the PF-07038124 group and 36.1 [13.9] years in the vehicle group) and 34 with plaque psoriasis (20 men [58.8%]; mean [SD] ages, 51.8 [12.3] years in the PF-07038124 group and 51.2 [10.8] years in the vehicle group). Baseline characteristics were generally balanced. At week 6, the PF-07038124 groups showed significantly greater improvements compared with vehicle groups in EASI (least-squares mean CFB, -74.9% vs -35.5%; difference, -39.4% [90% CI, -58.8% to -20.1%]; P < .001) and PASI scores (CFB, -4.8 vs 0.1; difference, -4.9 [90% CI, -7.0 to -2.8]; P < .001). The number of patients with treatment-emergent adverse events was comparable between treatment groups in patients with AD (PF-07038124, 9 [25.0%]; vehicle, 9 [26.5%]) and plaque psoriasis (PF-07038124, 3 [17.6%]; vehicle, 6 [35.3%]). There were no application site reactions with PF-07038124 treatment.
CONCLUSIONS AND RELEVANCE
Topical PF-07038124 was well tolerated and demonstrated superior efficacy compared with vehicle in patients with mild to moderate AD and plaque psoriasis.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04664153.
Topics: Male; Humans; Female; Adult; Middle Aged; Dermatitis, Atopic; Double-Blind Method; Psoriasis; Treatment Outcome; Ointments; Severity of Illness Index
PubMed: 38117526
DOI: 10.1001/jamadermatol.2023.4990 -
Neuromodulation : Journal of the... Jul 2023Staphylococcus aureus (S aureus) is the foremost bacterial cause of surgical-site infection (SSI) and is a common source of neuromodulation SSI. Endogenous colonization... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Staphylococcus aureus (S aureus) is the foremost bacterial cause of surgical-site infection (SSI) and is a common source of neuromodulation SSI. Endogenous colonization is an independent risk factor for SSI; however, this risk has been shown to diminish with screening and decolonization.
MATERIALS AND METHODS
A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed, Cochrane Library, and Embase data bases from inception to January 1, 2022, for the purposes of identifying all studies reporting on the use of S aureus swabbing and/or decolonization before neuromodulation procedures. A random-effects meta-analysis was performed using the metaphor package in R to calculate odds ratios (OR).
RESULTS
Five observational cohort studies were included after applying the inclusion and exclusion criteria. The average study duration was 6.6 ± 3.8 years. Three studies included nasal screening as a prerequisite for subsequent decolonization. Type of neuromodulation included spinal cord stimulation in two studies, deep brain stimulation in two studies, intrathecal baclofen in one study, and sacral neuromodulation in one study. Overall, 860 and 1054 patients were included in a control or intervention (ie, screening and/or decolonization) group, respectively. A combination of nasal mupirocin ointment and a body wash, most commonly chlorhexidine gluconate soap, was used to decolonize throughout. Overall infection rates were observed at 59 of 860 (6.86%) and ten of 1054 (0.95%) in the control and intervention groups, respectively. Four studies reported a significant difference. The OR for intervention (screen and/or decolonization) vs no intervention was 0.19 (95% CI, 0.09-0.37; p < 0.001). Heterogeneity between studies was nonsignificant (I = 0.43%, τ = 0.00).
CONCLUSIONS
Preoperative S aureus swabbing and decolonization resulted in significantly decreased odds of infection in neuromodulation procedures. This measure may represent a worthwhile tool to reduce neuromodulation SSI, warranting further investigation.
Topics: Humans; Staphylococcus aureus; Mupirocin; Staphylococcal Infections; Surgical Wound Infection; Anti-Bacterial Agents
PubMed: 36198512
DOI: 10.1016/j.neurom.2022.07.013 -
Infection and Drug Resistance 2023Skin and soft tissue infection (SSTI) is a frequently encountered clinical disease, and Sanhuang ointment, a traditional Chinese medicine, is used to treat it. However,...
INTRODUCTION
Skin and soft tissue infection (SSTI) is a frequently encountered clinical disease, and Sanhuang ointment, a traditional Chinese medicine, is used to treat it. However, the pharmacological effect of Sanhuang ointment on SSTI and its underlying mechanism remains unclear. Here, we investigate the protective effect of Sanhuang ointment on (MRSA) infection in the skin and soft tissues and the underlying mechanism by network pharmacological analysis, followed by in vivo experimental validation.
METHODS
Via network pharmacology, the active components and disease targets of Sanhuang ointment were screened and intersected for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A rat model of skin and soft tissue infection was established, and pathological features were observed. Large, medium, and small-dose groups (1 g, 0.5 g, and 0.25 g/animal, with the total amount of Vaseline, dispensed 1 g/animal) of Sanhuang ointment were prepared and Mupirocin ointment was used as a positive control (0.5 g/animal, with the total amount of Vaseline, dispensed 1 g/animal). The expressions of key proteins of the IL-17/NF-κB signaling pathway and downstream inflammatory factors were analyzed by histomorphological analysis, enzyme-linked immunosorbent assay, polymerase chain reaction, and Western blotting.
RESULTS
In all, 119 active components and 275 target genes of Sanhuang ointment were identified and intersected with MRSA infection-related genes via network pharmacology analysis, and 34 target genes of Sanhuang ointment were found to be involved in skin and soft tissue infections with MRSA. Sanhuang ointment (1 g/mouse) could effectively ameliorate histopathological changes and significantly inhibit the expression of key proteins involved in the IL-17/NF-κB signaling pathway and downstream inflammatory factors (p < 0.05).
CONCLUSION
Sanhuang ointment has a protective effect on MRSA infection and inhibits inflammation by inhibiting the IL-17/NF-κB signaling pathway. Our findings are important for the secondary development and new drug development of Sanhuang ointment.
PubMed: 37954508
DOI: 10.2147/IDR.S424746 -
International Journal of Exercise... 2023This study investigated the efficacy of topical cannabidiol (CBD) ointment in reducing localized inflammation, minimizing performance detriments, and attenuating...
This study investigated the efficacy of topical cannabidiol (CBD) ointment in reducing localized inflammation, minimizing performance detriments, and attenuating soreness associated with delayed onset muscle soreness (DOMS). In a double blind randomized control trial, upper-arm circumferences, maximal voluntary isometric contractions (MVICs) for elbow flexion at 90° and 30° for college-aged participants ( = 21, age 20.8 ± 1.9 years) were assessed at baseline. Participants then performed a DOMS-inducing protocol for the biceps brachii. Topical CBD ointment and placebo (P) ointment were randomly assigned and applied 30 minutes, 24, 48 and 72 hours post the DOMS protocol. The baseline parameters and a visual analog scale (VAS) to assess perceived soreness were assessed 24, 48 and 72 hours post DOMS protocol. A 4x2 repeated measures factorial ANOVA ( < 0.05) analyzed both within and between subject differences. No changes were statistically significant on any days between conditions: Upper-arm circumferences in the CBD arm (7.1 ± 5.8 cm) and in the P arm (7.3 ± 5.8 cm). MVICs were reduced at both the 90° and 30° positions (-5.9 ± 9.0 Nm (90°)); (-4.8 ± 6.5 Nm (30°)) and the P arm (-5.0 ± 10.0 Nm (90°)); (-4.6 ± 5.3 Nm (30°)). Soreness increased in both the CBD arm (6.1 ± 2.1) and the P arm (5.5 ± 2.6) over time. Topical CBD therefore did not alter any parameters vs the P treatment, thus the use of topical CBD does not attenuate the effects of DOMS.
PubMed: 38287971
DOI: No ID Found