Intra-articular Injection Of Drugs Research Articles

Self-reinforced MOF-based Nanogel Alleviates Osteoarthritis by Long-acting Drug Release.

Intra-articular injection of drugs is an effective strategy for osteoarthritis (OA) treatment. However, the complex microenvironment and limited joint space result in rapid clearance of drugs. Herein, a nanogel-based strategy was proposed for prolonged drug delivery and microenvironment remodeling. Nanogel was constructed through functionalization of hyaluronic acid (HA) by amide reaction on the surface of Kartogenin (KGN)-loaded zeolitic imidazolate framework-8 (denoted as KZIF@HA). Leveraging the inherent hydrophilicity of HA, KZIF@HA spontaneously forms nanogels, ensuring extended drug release in the OA microenvironment. KZIF@HA exhibits sustained drug release over one month, with low leakage risk from the joint cavity compared to KZIF, enhanced cartilage penetration, and reparative effects on chondrocytes. Notably, KGN released from KZIF@HA serves to promote extracellular matrix (ECM) secretion for hyaline cartilage regeneration. Zn2+ release reverses OA progression by promoting M2 macrophage polarization to establish an anti-inflammatory microenvironment. Ultimately, KZIF@HA facilitates cartilage regeneration and OA alleviation within three months. Transcriptome sequencing validates that KZIF@HA stimulates the polarization of M2 macrophages and secretes IL-10 to inhibit the JNK and ERK pathways, promoting chondrocytes recovery and enhancing ECM remodeling. This pioneering nanogel system offers new therapeutic opportunities for sustained drug release, presenting a significant stride in OA treatment strategies. This article is protected by copyright. All rights reserved.

Research progress on early postoperative pain management strategies after arthroscopic anterior cruciate ligament reconstruction

To summarize the early postoperative pain management strategies for anterior cruciate ligament reconstruction (ACLR), and to select a reasonable and effective pain management plan to promote functional rehabilitation after ACLR. The literature about the early postoperative pain management strategies of ACLR both domestically and internationally in recent years was extensiverly reviewed, and the effects of improving postoperative pain were reviewed. Currently, physical therapy and oral medication have advantages such as economy and simplicity, but the effect of improving postoperative pain is not satisfactory, often requires a combination of intravenous injection or intravenous pump, which is also a common way to relieve pain. However, in order to meet the analgesic needs of patients, the amount of analgesic drugs used is often large, which increases the incidence of various adverse reactions. Local infiltration analgesia (LIA), including periarticular or intra-articular injection of drugs, can significantly improve the early postoperative pain of ACLR, and achieve similar postoperative effectiveness as nerve block. LIA can be used as an analgesic technique instead of nerve block, and avoid the corresponding weakness of innervated muscles caused by nerve block, which increases the risk of postoperative falls. Many studies have confirmed that LIA can alleviate postoperative early pain in ACLR, especially the analgesic effects of periarticular injection are more satisfactory. It can also avoid the risk of cartilage damage caused by intra-articular injection. However, the postoperative analgesic effect and timeliness still need to be improved. It is possible to consider combining multimodal mixed drug LIA (combined with intra-articular and periarticular) with other pain intervention methods to exert a synergistic effect, in order to avoid the side effects and risks brought by single drugs or single administration route. LIA is expected to become one of the most common methods for relieving postoperative early pain in ACLR. Early pain after arthroscopic ACLR still affects the further functional activities of patients, and all kinds of analgesic methods can achieve certain effectiveness, but there is no unified standard at present, and the advantages and disadvantages of various analgesic methods need further research.

ЛЕЧЕНИЕ ГНОЙНЫХ ГОНИТОВ

Purulent gonitis that has arisen after knee replacement, osteosynthesis with fractures of the bones forming the knee joint, arthroscopy, and the introduction of medications is a serious complication, the treatment of which is a social and economic problem. The aim of our study was to evaluate the effectiveness of the choice of treatment tactics for patients with purulent gonitis according to their etiology, local changes in the joint as well as the type and resistance of the infection causative agent. The analysis of the treatment of 154 patients was carried out. In most cases, 97 patients (63%), gonitis was noted in the form of the periprosthetic joint infection (PJI). In 33 (21%) cases it was noted with postoperative osteoarthritis after osteosynthesis of intra-articular fractures of the bones forming the knee joint. After arthroscopy with knee joint ligament surgery — 10 (7%) cases, intra-articular injections of drugs into the knee joint — 14 (9%). The high effectiveness of sanitizing treatment was achieved in 146 (94,8%) cases. 93 (95,8%) of the patients had PJI, 32 (96,9%) had postoperative osteomyelitis, 9 (90%) had arthroscopy, and 12 (85,7%) had intra-articular drug injections. The tactics of treatment of purulent gonitis depends on the etiology and nature of the joint lesion, the resistance of the microorganism, and the comorbid condition of patients.

Role of WNT Agonists, BMP and VEGF Antagonists in Rescuing Osteoarthritic Knee Cartilage in a Rat Model.

The superficial zone of articular cartilage (AC) is vital for its function and biomechanics. The damaged AC gets vascularized and undergoes hypertrophy and ossification. Studies have highlighted these two as the major causative factors in osteoarthritis (OA). We aimed at preventing the OA progression in a rat knee instability model by inhibiting the vascular ingrowth and ossification using VEGF and BMP antagonist. A WNT agonist was also used to promote AC regeneration because of its protective effect on the superficial layer. Rat knee OA was created by surgical excision of the medial meniscus and medial collateral ligament. Forty rats were divided into two groups of twenty each for surgical control and tests (surgery + intra-articular injection of drugs every two weeks). Ten animals from each group were sacrificed at four and eight weeks. Histology was mainly used to evaluate the outcome. A surgical OA model was successfully created with higher histological scores for operated knees, both in short- (P = 0.0001) and long-term (P = 0.001). Modified Mankin score was lesser in the test animals as compared to control (P = 0.17) in the short-term, but the trend was reversed in the long-term (P = 0.13). Subgroup analysis revealed that repeated injections in the anterolateral compartment contributed to higher scores in the lateral (P = 0.03) and anterior (P = 0.03) compartment of the knee in the long-term. The combinatorial approach was effective in controlling the OA in short-term. Further studies are needed to test the sustained drug delivery system to improve the outcome.

Diffusion of neutral solutes within human osteoarthritic cartilage: Effect of loading patterns

ObjectiveVariation of the solute diffusion within articular cartilage is an important feature of osteoarthritis (OA) progression. For in vitro study of monitoring of the diffusion process, it is essential to simulate physiological conditions as much as possible. Our objective was to investigate the effects of loading patterns on diffusion processes of neutral solutes within osteoarthritic cartilage. MethodsOsteochondral plugs were harvested from human tibial plateaus and separated into three OA stages according to modified Mankin scoring system. The samples were subjected to static or cyclic compression using a carefully designed loading device. Contrast-enhanced micro-computed tomography (CEμCT) was applied to acquire image sequences while the cartilage was being compressed. The apparent diffusion maps and diffusion coefficients were analysed, as well as histological and stereological assessments of the plugs. ResultsThe diffusion of neutral solutes was significantly affected by the loading patterns. For OA cartilage with early and middle stages, cyclic loading accelerated contrast agent infiltration compared with static loading. However, for late-stage OA samples, no acceleration of diffusion was observed in the first 2 ​h because of the insufficient resilience of compressed cartilage. The accumulation of neutral solutes in an upward invasive fissure also suggested that solutes could penetrate into the fissure under cyclic loading. ConclusionsTo our knowledge, this is the first study to combine the cyclic compression and CEμCT scanning in the diffusion testing of human OA cartilage. This loading pattern could simulate the physiological conditions and reduce the time to reach solute equilibrium within cartilage. The diffusion data may contribute to joint drug-injection therapies for early OA. The translational potential of this articleThe combination of cyclic loading and CEμCT scanning enabled diffusion analysis of osteoarthritic cartilage under different compressions. A comprehensive evaluation of OA cartilage and subchondral bone may benefit from this technique. The diffusion data provide theoretical support and reference for intra-articular injection of drugs.

Síndrome de Nicolau. Manejo conservador. Caso clínico

Introducción: el síndrome de Nicolau, embolia cutis o dermatitis livedoide, es una reacción adversa poco frecuente a la administración de inyección intramuscular, subcutánea o intraarticular de medicamentos, inicia con dolor intenso y eritema que evoluciona a lesión livedoide que se torna hemorrágica, progresa a necrosis isquémica de piel y tejidos más profundos.
 Caso clínico: niño de 7 meses de edad, luego de inyección intramuscular de metamizol sódico presenta llanto continuo, seguido de lesión purpúrica afectando espalda, glúteo, muslo y pierna derechos, evolucionando hasta cicatrización total en 18 semanas.
 Conclusión: el síndrome de Nicolau, condición iatrogénica por inyección de múltiples medicamentos, produce lesión necrótica en área de irrigación de vasos afectados. El conocimiento de este síndrome facilitaría su prevención, al igual que su diagnóstico y manejo tempranos.

Determining the Risk of Septic Arthritis Following Intra-Articular Injection of Drugs Mixed At A Tertiary Care Center, 2012–2017

BACKGROUND Intra-articular corticosteroid injections are commonly used for the outpatient treatment of osteoarticular pain. Practitioners may choose to administer additional medications such as anesthetics. While medications are compounded in the pharmacy following stringent environmental requirements, occasionally injections with additional components for immediate use are mixed at the point of care under less strict environmental conditions due to turnaround time requirement. We assessed if mixing multiple drugs in a single syringe in outpatient settings was associated with subsequent septic arthritis. METHODS We reviewed electronic pharmacy medication administration records of patients who received an intra-articular corticosteroid injection at a tertiary care center during 2012–2017. We extracted basic patient demographics. Exposure was defined as receiving more than one intra-articular medication during a single injection-encounter. The outcome was culture-confirmed septic arthritis defined as a?positive synovial fluid culture within 90?days following an intra-articular?injection. We present case counts, ranges, and frequencies. RESULTS 7,072 unique patients received an intra-articular injection. Mean age was 55?years (range: 9 – 104) and 41% were male. There were 13,089 distinct intra-articular injection-encounters. Of the unique encounters, 306 (2%) intra-articular injection involved only one medication; 12,080 (92%) received 2 medications; 596 (5%) received 3 medications; 104 (0.8%) received 4 medications; and 3?(0.02%) received 5 medications. There were no infections following single intra-articular medication injection-encounters. Two septic arthritis cases were identified in patients who received two intra-articular medications (triamcinolone and lidocaine 1%). The microorganisms were: Staphylococcus aureus and Enterobacter cloacae. CONCLUSIONS Intra-articular corticosteroid injection practices in outpatient settings are heterogeneous. Septic arthritis following intra-articular injection was infrequent. We were unable to associate septic arthritis with mixing intra-articular injectables outside the pharmacy.

МАЛОИНВАЗИВНЫЕ МЕТОДЫ ЛЕЧЕНИЯ ДИСКОГЕННОЙ БОЛИ И ФАСЕТОЧНОГО СИНДРОМА В ПОЯСНИЧНОМ ОТДЕЛЕ ПОЗВОНОЧНИКА: ОБЗОР ЛИТЕРАТУРЫ И СОБСТВЕННЫЕ КЛИНИЧЕСКИЕ РЕЗУЛЬТАТЫ

Pain in the lumbar spine is the most common among people of working age. All open surgery, including endoscopic, to eliminate a disc-radicle conflict, associated with a large number of complications. This increasingly encourages doctors to use conservative and minimally invasive techniques. This article presents modern methods of treatment of facet syndrome: chemical denervation, radiofrequency ablation, intraarticular injection of drugs into the cavity in the intervertebral joints. Further research work revealed modern methods of treatment of elimination of a disc-radicle conflict: chemical denervation of the disc, chemonucleolysis, mechanical decompression, intradiscal used electrothermal therapy, laser nucleotomy, hydrodiscectomy, nucleoplasty, laser disc reconstruction. The pathogenetic substantiation of the above methods is considered, the positive and negative sides of each of them are revealed. Presented their own clinical results the Results showed a 70-80% efficiency in the next observation period without serious complications.

Cost-effectiveness of Different Intra-articular Drug Injections on Wrist and/or Elbow Compromise in Patients With Established Rheumatoid Arthritis: Short-term Results of an Open Observational Evaluation.

Intra-articular (IA) injections are an integral part of the management of rheumatoid arthritis (RA). However, there are few reports regarding the association between drug effectiveness and cost. The aim of this study was to assess the cost-effectiveness of various combinations of IA injections of betamethasone, hyaluronic acid (HA) or etanercept for oligoarthritis in RA. Seventy RA patients were assigned to 4 groups according to the IA injection drug(s): betamethasone alone, betamethasone + etanercept, betamethasone + HA, or etanercept alone. Data for the following were collected before and after IA injection: erythrocyte sedimentation rate, C-reactive protein (CRP), disease activity score in 28 joints calculated with CRP, and patient global visual analog scale. In addition, power Doppler ultrasonography and gray-scale ultrasonography scores were obtained for synovitis, and passive range of motion of joints was measured. Sixty-eight RA patients completed the trial. Compared with patients given etanercept alone, the visual analog scale, power Doppler ultrasonography, and gray-scale ultrasonography scores of each of the other groups were significantly better at each time point. At 1 month, the passive range of motion of joints in patients given betamethasone + HA was significantly better than that of each of the other groups. Synovial hyperplasia improved significantly in all groups, but less so in those given etanercept alone. All other clinical parameters of the 4 groups were similar. The costs per joint for the betamethasone-alone, betamethasone + etanercept, betamethasone + HA, and etanercept-alone groups were, respectively, $7.55, $181.77, $42.68, and $174.22. Intra-articular injection of betamethasone alone was the most cost-effective treatment for oligoarthritis of RA. Betamethasone combined with HA injection resulted in the best improvement in joint function.

Intra-articular drug injections in the combination treatment of rheumatic diseases

In clinical practice, intra-articular injections of glucocorticoids (GC) are widely used to treat chronic joint inflammatory diseases, osteoarthritis (OA), and extra-articular soft tissue involve-ment. GCs given to patients with chronic arthritis may rapidly suppress joint inflammatory changes and ensure significant clinical improvements well before there is a benefit of prescribed disease-modifying antirheumatic drugs. According to the clinical features of disease, GCs may be used for systemic or local treatment in each specific case and a combination of these two treatments may be performed in some patients. In OA patents, the effect of intra-articular GC injections is less sustained than in those with joint inflammatory diseases and it persists for an average of about 3 weeks. Intra-articular hyaluronic acid is likely to be a more promising treatment for OA. It may also relieve pain considerably and improve joint functions. At the same time the highest effect was noted between weeks 5 and 13 after injection, but improvement also persisted after 14–26 weeks or longer in a number of cases.

Clinical and biochemical characteristics after intra-articular injection for the treatment of osteoarthritis of the knee: prospective randomized study of sodium hyaluronate and corticosteroid

BackgroundIntra-articular injections of sodium hyaluronate (Na-HA) and corticosteroid (CS) are often used for the treatment of osteoarthritis (OA), and the clinical usefulness of such treatment has been reported. Some studies have discussed the effectiveness of intra-articular drug injection therapy in terms of the clinical results, but no cohort studies have performed evaluations of effectiveness based on changes in joint biomarkers. This prospective randomized study compared the efficacy of Na-HA and CS injections based on clinical scores and levels of biochemical markers for osteoarthritis. MethodsA total of 51 patients with knee osteoarthritis received intra-articular injections of either Na-HA or CS and were followed for 6 months after treatment. Pain and inflammatory scores were evaluated at the baseline, at 5 weeks, and at 6 months. We also measured joint fluid levels of hyaluronan (HA), chondroitin 6-sulfate, chondroitin 4-sulfate, matrix metalloproteinase (MMP)-9, and tissue inhibitor of MMP (TIMP)-1 at the baseline and at 5 weeks. ResultsIn both groups, injection therapy significantly improved pain/inflammation scores and visual analog scale scores with time (P < 0.01). HA levels were significantly increased after injection only in the Na-HA group (P < 0.05); and the MMP-9 level decreased significantly after injection only in the Na-HA group (P < 0.01). Other marker levels did not differ significantly between groups. ConclusionsThe results of this prospective randomized study suggest that the clinical effects of Na-HA and CS as local therapies for OA are comparable and that both drugs are useful. Considering the results of the measurement of biomarkers, compared with CS injection therapy Na-HA injection therapy may have protective effects on the articular cartilage by increasing the HA concentration in synovial fluid, as well as inhibitory effects on the catabolism of articular cartilage by reducing the MMP-9 concentration.

Poster 43: Sodium Iodoacetate Induced Osteoarthritis Model in Rabbit Temporomandibular Joint

Statement of the Problem: A series of experimental studies showed that surgical induction of anterior disc displacement led to the degenerative changes in the condylar cartilage. However, this surgical procedure induced not only mechanical alteration but also artificial surgical damage to the joint structures. Structural models generate osteoarthritic changes similar to those observed in humans by intra-articular injection of drugs targeting articular cells, mainly condrocytes. Chondrocyte metabolism inhibitor, MIA, has been reported to induce the disruption of glycolysis and subsequently cell death and the loss of chondrocytes. MIA injection induced to various histological changes in the knee joints closely resemble to human osteoarthritis (OA). Although the biological action of this drug has been well documented in the knee joints, only one animal study reported the injection of 1.5 mg MIA into the joint without disc derangement and joint capsule opening. The aim of this study was to determine MIA induced osteoarthritis in rabbit TMJ for using different dosage and time intervals. The null hypothesis is to find the most appropriate dosage of MIA and shortest time to induce osteoarthritis in TMJ without surgery and joint capsule opening like as clinically usage of arthrocentesis in humans. For this purpose, we investigated radiologic, histologic and histomorphometric findings of the four different concentrations of MIA (1.5, 2, 2.5, 3 mg/mL) to create osteoarthritic changes in rabbit TMJ within 3 different time intervals (2, 4 and 6 weeks).

An intra-articular method for assessing topical application to a synovial joint

Intra-articular injection of drugs is increasingly used in human medicines. We report a method for the direct administration of a test substance to the synovial fluid of the canine stifle joint. This method caused little distress or pathology, making it suitable for pre-clinical assessment of new drugs in dogs and other species.

An intra-articular method for assessing topical application to a synovial joint

Intra-articular injection of drugs is increasingly used in human medicines. We report a method for the direct administration of a test substance to the synovial fluid of the canine stifle joint. This method caused little distress or pathology, making it suitable for pre-clinical assessment of new drugs in dogs and other species.

Rabbit monoarticular arthritis as a model for intra-articular drug injections. The local action of administered cortisol and alpha-1 proteinase inhibitor.

Monoarticular arthritis in the rabbit has been used to study the effect of intra-articular administration of cortisol-21-phosphate and alpha-1-proteinase inhibitor. The preparations were administered both separately and in combination. All treatments improved parameters associated with joint biochemistry and histopathology, but the greatest effect was found when steroid was combined with anti-proteinase. Cortisol-21-phosphate had both an anti-inflammatory and anti-arthritic action, whereas alpha-1-proteinase inhibitor showed little anti-inflammatory action but had some anti-arthritic effect. Alpha-1-proteinase inhibitor had no anti-inflammatory action against carrageenan induced oedema in the rat, but was anti-arthritic against adjuvant induced arthritis in the rat where it reduced both primary and secondary arthritis.

Response of synovial immunocytes to intra-articular agents in experimental arthritis.

In rabbits with immune arthritis the numbers of lymphoid aggregates and pyroninophilic and non-pyroninophilic cells per unit area of synovium were calculated from sections taken at various intervals after intra-articular drug injections. A model of immune arthritis based on the results is presented. In the active phase of the arthritis, plasma cells, plasmablasts and lymphoid aggregates proliferate, while the number of lymphocytes decreases. In the inactive phase after treatment, the cell pattern is the reverse. The ratio of pyroninophilic to non-pyroninophilic cells proved to be a good measure of the activity of the arthritis. A favourable therapeutic effect was achieved with triamcinolone hexacetonide and combined steroid-osmic acid, but not with osmic acid alone.