Nanosuspension-Loaded Dissolving Microneedle Patches for Enhanced Transdermal Delivery of a Highly Lipophilic Cannabidiol.

Purpose: Transdermal Drug Delivery System (TDDS) offers a promising alternative for delivering poorly soluble drugs, challenged by the stratum corneum's barrier effect, which restricts the pool of drug candidates suitable for TDDS. This study aims to establish a delivery platform specifically for highly lipophilic drugs requiring high doses (log P > 5, dose > 10 mg/kg/d), to improve their intradermal delivery and enhance solubility. Methods: Cannabidiol (CBD, log P = 5.91) served as the model drug. A CBD nanosuspension (CBD-NS) was prepared using a bottom-up method. The particle size, polydispersity index (PDI), zeta potential, and concentration of the CBD-NS were characterized. Subsequently, CBD-NS was incorporated into dissolving microneedles (DMNs) through a one-step manufacturing process. The intradermal dissolution abilities, physicochemical properties, mechanical strength, insertion depth, and release behavior of the DMNs were evaluated. Sprague-Dawley (SD) rats were utilized to assess the efficacy of the DMN patch in treating knee synovitis and to analyze its skin permeation kinetics and pharmacokinetic performance. Results: The CBD-NS, stabilized with Tween 80, exhibited a particle size of 166.83 ± 3.33 nm, a PDI of 0.21 ± 0.07, and a concentration of 46.11 ± 0.52 mg/mL. The DMN loaded with CBD-NS demonstrated favorable intradermal dissolution and mechanical properties. It effectively increased the delivery of CBD into the skin, extended the action's duration in vivo, and enhanced bioavailability. CBD-NS DMN exhibited superior therapeutic efficacy and safety in a rat model of knee synovitis, significantly inhibiting TNF-α and IL-1ß compared with the methotrexate subcutaneous injection method. Conclusion: NS technology effectively enhances the solubility of the poorly soluble drug CBD, while DMN facilitates penetration, extends the duration of action in vivo, and improves bioavailability. Furthermore, CBD has shown promising therapeutic outcomes in treating knee synovitis. This innovative drug delivery system is expected to offer a more efficient solution for the administration of highly lipophilic drugs akin to CBD, thereby facilitating high-dose administration.

Novel inflammatory markers in the blood of patients with knee synovitis.

OBJECTIVE: Synovitis is a joint disease that seriously affects patient quality of life, but there are currently no diagnostic markers. The albumin to fibrinogen ratio (AFR) and monocyte to lymphocyte ratio (MLR) are non-invasive and cost-effective markers for various systemic inflammatory diseases. However, these markers have not yet been investigated for synovitis. This cross-sectional study evaluated the predictive ability of AFR and MLR in patients with non-specific knee synovitis. METHODS: One hundred fifty-five patients with knee synovitis and 108 healthy control patients were enrolled. Patient characteristics, blood parameters, AFRs, and MLRs were assessed, and the diagnostic value of these factors was determined. RESULTS: Among 125 patients included, patients with synovitis had a lower AFR and higher MLR than control subjects. The diagnostic values of AFR and MLR were 0.86 and 0.84, respectively, and higher compared with other parameters by receiver operating characteristic curve assessments. Additionally, MLR was negatively correlated with AFR. Late-stage patients showed significantly lower AFRs and significantly higher MLRs than early-stage patients. Binary logistic regression analyses indicated that AFR was an independent predictor for synovitis severity. CONCLUSIONS: The AFR and MLR had high diagnostic value for knee synovitis. The AFR was an independent predictor for synovitis severity.

Effect of Modified Simiaosan on Inflammatory Factors and Neuropeptide Substances of Patients with Synovitis of Knee Joint and Damp-heat Obstruction Collateral Syndrome / 中国实验方剂学杂志

Objective::To observe the clinical efficacy of modified Simiaosan on synovitis of knee joint with damp-heat obstruction collateral syndrome and the effect on inflammatory factors and neuropeptide substances in synovial fluid. Method::One hundred and thirty-five patients were randomly divided into control group(67 cases) and observation group(68 cases) by random number table. Patients' intra-articular effusion was drawn out. Triamcinolone acetonide was injected into arthrosis for 2 times, 1 time/week, and aceclofenac sustained-release tablets were given for 4 weeks, 0.2 g/time, 1 time/day. In addition to the therapy of control group, patients in observation group were also given modified Simiaosan for 4 weeks, 1 dose/day. Before and after treatment, pain, swelling of knee joint and were scored, Western Ontario and McMaster University (WOMAC) were adopted for scoring knee score, and damp-heat obstruction syndrome and local signs of knee joint were also assessed. And levels of interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), hypersensitive C-reactive protein (hs-CRP), substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) were detected. Result::After treatment, scores of pain and swelling of knee joint in observation group were lower than those in control group (P<0.01). Scores of WOMAC, the total score, integral of damp-heat obstruction collateral syndrome, knee flexion-extension range score and floating patella test were all lower than those in control group (P<0.01). And levels of IL-1β, IL-6, TNF-α, hs-CRP, SP, CGRP, NPY and VIP were all lower than those in control group (P<0.01). Analyzed by rank sum test, the clinical efficacy in observation group was better than those in control group (Z=2.089, P<0.05). Conclusion::Modified Simiaosan can significantly alleviate pain and swelling symptoms, promote the recovery of knee joint function, and inhibit the expressions of proinflammatory factors and neuropeptides in synovial fluid, with a better clinical efficacy.

Sinovitis de rodilla, su tratamiento en el área terapéutica de la Facultad de Cultura Física "Nancy Uranga Romagoza" / Knee synovitis, their treatment in the therapeutic room at the Faculty of Physical Culture "Nancy Uranga Romagoza"

RESUMEN El trabajo que se realizó tiene como objetivo proponer ejercicios terapéuticos y masaje que contribuyan al tratamiento de la sinovitis de rodilla en pacientes que asisten al área terapéutica de la Facultad de Cultura Física «Nancy Uranga Romagoza¼, Pinar del Río; teniendo en cuenta que a pesar de un mes de tratamiento los pacientes presentaban limitación articular, claudicación de la marcha y disminución del tono de los músculos que participan en los movimientos de esa articulación, lo que influye negativamente en la rehabilitación de su lesión. El empleo de métodos teóricos como histórico-lógico, análisis-síntesis e inductivo-deductivo; de métodos empíricos como el análisis con documentos y la medición, así como los métodos estadísticos, posibilitaron constatar las limitaciones en la amplitud articular de la rodilla lesionada, además estructurar la propuesta cuyos ejercicios terapéuticos tienen como principios entre otros, la regulación de las cargas, la sistematicidad e ir de lo simple a lo complejo; estructurada en dos etapas, inicial y avanzada, así como la vinculación con el masaje, de forma tal que incida positivamente en la recuperación del paciente, constatando la utilidad en su aplicación. Se hace alusión a la importancia de la participación activa del lesionado para la efectividad de la terapia y recomienda continuar el estudio de los factores que influyen en un mejor tratamiento rehabilitador para pacientes con sinovitis de rodilla.

ABSTRACT This work is aimed at proposing therapeutic exercises and massages to contribute to the treatment of the knee synovitis in patients who assisted tothe therapeutic area of the Physical Culture Faculty «Nancy UrangaRomagoza¼, Pinar del Río; Taking into account that in spite of a month of treatment the patients presented limitation to articulate, reduction of the walk motion and decrease of the muscular tone of the muscles that participate in the movements of that articulation, influencing negatively in the rehabilitation of their injury. The usage of theoretical methods as historical-logical, analysis-synthesis and inductive-deductive; of empiric methods as the analysis with documents and the measuring experiment, as well as the statistical methods, facilitated to verify the limitations in the joint width around the injured knee, also to structure the proposal whose therapeutic exercises having as a principle, the regulation of the loads increasing gradually the complexity levels, structured in two stages, initial and advanced, as well as the linking to the massage, in such way that impacts positively in the patient's recovery. In the conclusions there is a reference to the importance of the patient´s active participation on behalf of the effectiveness of the therapy and it is recommended to continue the study of the factors that determine a better rehabilitation treatment for patients suffering knee synovitis.

Validity of Radiograph-Based Infrapatellar Fat Pad Opacity Grading for Assessing Knee Synovitis: Correlation With Contrast-Enhanced MRI.

OBJECTIVE: The purpose of this study was to determine the validity of infrapatellar fat pad (IPFP) opacity grading based on lateral knee radiography for assessing knee synovitis using correlation with contrast-enhanced (CE) MRI. MATERIALS AND METHODS: Retrospective reviews of radiographs and CE knee MR images from 79 patients were independently performed by two radiologists. They evaluated IPFP opacity alteration (IPFPCR) and joint effusion grades on lateral knee conventional radiographs, IPFP signal intensity alteration (IPFPMR) and joint effusion grades on CE MR images, and synovitis (SYNMR) grade in nine divided regions, three compartments (parapatellar, periligamentous, perimeniscal), and the whole knee on CE MR images. Correlations between radiographic grades and MRI assessments were evaluated using Spearman correlation tests, and the correlation coefficients (ρ) were compared. Interobserver agreement was evaluated using weighted kappa values. RESULTS: The IPFPCR grade was very highly correlated with the IPFPMR grade (ρ = 0.906, p < 0.001) and highly correlated with SYNMR grades from four regions (suprapatellar, infrapatellar, intercondylar, lateral parapatellar recess), the parapatellar compartment, and the whole knee (ρ = 0.614-0.740, all p < 0.001). The IPFPCR grade was moderately correlated with the SYNMR grades of the remaining five regions and two compartments (ρ = 0.457-0.547, all p < 0.001). The differences between correlation coefficients for SYNMR grades and the IPFPCR and IPFPMR grades were not statistically significant (p = 0.290-1.0). Interobserver reliabilities were excellent or good for IPFPCR, IPFPMR, and SYNMR grades (κ = 0.661-1.000). CONCLUSION: IPFPCR grade assessment enables valid evaluation and reporting of knee synovitis, especially in the parapatellar compartment and the whole knee.

Poncet's disease (tubercular rheumatism) with primary involvement of the foot - A case report.

We present a rare case with primary tubercular involvement of the foot, accomapanied by a reactionary (aseptic) effusion in the knee. The diagnosis was delayed due to unusual presentation and also because of failure to elicit a detailed history. Incision and drainage of the foot abscess and antitubercular drug therapy resulted in satisfactory control of tubercular infection. Polyarticular presentation may not always signify active tubercular focus in every joint; it may reflect reactive synovitis known as Poncet's disease, which resolves with multidrug antitubercular therapy.A multidispilinary approach should be adopted and chest physicians, rheumatologists and orthopaedic surgeons should work in close association to correctly diagnose and treatthis condition.

Effects Analysis of Joint Function and MMP-7 and MMP-9 Measurement after Synovial Arthroscopic Debridement for Knee Synovitis / 现代检验医学杂志

Objective To investigate effects analysis of joint function and MMP-7 and MMP-9 measurement after synovial ar-throscopic debridement for knee synovitis.Methods 72 patients with knee synovitis method based on a random draw were e-qually divided into the treatment group and the control group,the control group were given the traditional synovial planing surgery.The treatment group were given the arthroscopic debridement synovium.Results After treatment,the response rates in the treatment group and the control group were 97.2% and 80.6% respectively.The response rate of the treatment group were significantly better than the control group.The difference was statistically significant (P <0.05).The postopera-tive Lysholm scores were increased significantly,while the pain scores were significantly reduced,and the postoperative Ly-sholm score and pain scores difference compared between the two groups were also statistically significant.The difference was statistically significant (P <0.05).The postoperative synovial tissue MMP-7 and MMP-9 expression rates were in the two groups significantly lower.The difference was statistically significant (P <0.05),while the postoperative MMP-7 and MMP-9 expression rates of the treatment group were ignificantly lower than the control group (P <0.05).Conclusion Syn-ovial arthroscopic debridement for knee synovitis can relieve pain and improve knee function,reduce the expression of MMP-7 and MMP-9,thereby enhance the overall efficacy of the treatment.