Particles for Local Delivery of Proteins Using Intra-Articular Route.
Ontology highlight
ABSTRACT:
SUBMITTER: Khodabandehlou K
PROVIDER: S-EPMC4852977 | biostudies-literature | 2016 Mar
REPOSITORIES: biostudies-literature
Publications
Particles for Local Delivery of Proteins Using Intra-Articular Route.
Khodabandehlou Khosrow K Tian Shaomin S Luft James C JC Khan Saad A SA DeSimone Joseph M JM
Advanced healthcare materials 20160202 6
Designing a vehicle for local delivery of proteins using intra-articular route is an attractive option to minimize the adverse effects associated with systemic exposure and to maximize the efficacy. Slowly dissolving silylated microparticles are designed with specific size and shape that are capable of extending the retention time of a model protein (bovine serum albumin) in the murine knee joint. No cytotoxicity is observed for the reconstituted formulation when tested against synovial fibrobla ...[more]
Similar Datasets
Project description:Osteoarthritis (OA) is a debilitating joint disorder affecting more than 240 million people. There is no disease modifying therapeutic, and drugs that are used to alleviate OA symptoms result in side effects. Recent research indicates that inhibition of peroxisome proliferator-activated receptor ? (PPAR?) in cartilage may attenuate the development or progression of OA. PPAR? antagonists such as GSK3787 exist, but would benefit from delivery to joints to avoid side effects. Described here is the loading of GSK3787 into poly(ester amide) (PEA) particles. The particles contained 8 wt.% drug and had mean diameters of about 600 nm. Differential scanning calorimetry indicated the drug was in crystalline domains in the particles. Atomic force microscopy was used to measure the Young's moduli of individual particles as 2.8 MPa. In vitro drug release studies showed 11% GSK3787 was released over 30 days. Studies in immature murine articular cartilage (IMAC) cells indicated low toxicity from the drug, empty particles, and drug-loaded particles and that the particles were not taken up by the cells. Ex vivo studies on murine joints showed that the particles could be injected into the joint space and resided there for at least 7 days. Overall, these results indicate that GSK3787-loaded PEA particles warrant further investigation as a delivery system for potential OA therapy.
| S-EPMC7240550 | biostudies-literature
Project description:Most forms of arthritis are incurable, difficult to treat, and a major cause of disability in Western countries. Better local treatment of arthritis is impaired by the pharmacokinetics of the joint that make it very difficult to deliver drugs to joints at sustained, therapeutic concentrations. This is especially true of biologic drugs, such as proteins and RNA, many of which show great promise in preclinical studies. Gene transfer provides a strategy for overcoming this limitation. The basic concept is to deliver cDNAs encoding therapeutic products by direct intra-articular injection, leading to sustained, endogenous synthesis of the gene products within the joint. Proof of concept has been achieved for both in vivo and ex vivo gene delivery using a variety of vectors, genes, and cells in several different animal models. There have been a small number of clinical trials for rheumatoid arthritis (RA) and osteoarthritis (OA) using retrovirus vectors for ex vivo gene delivery and adeno-associated virus (AAV) for in vivo delivery. AAV is of particular interest because, unlike other viral vectors, it is able to penetrate deep within articular cartilage and transduce chondrocytes in situ. This property is of particular importance in OA, where changes in chondrocyte metabolism are thought to be fundamental to the pathophysiology of the disease. Authorities in Korea have recently approved the world's first arthritis gene therapy. This targets OA by the injection of allogeneic chondrocytes that have been transduced with a retrovirus carrying transforming growth factor-?1 cDNA. Phase III studies are scheduled to start in the United States soon. Meanwhile, two additional Phase I trials are listed on Clinicaltrials.gov , both using AAV. One targets RA by transferring interferon-?, and the other targets OA by transferring interleukin-1 receptor antagonist. The field is thus gaining momentum and promises to improve the treatment of these common and debilitating diseases.
| S-EPMC5773261 | biostudies-literature
Project description:The histone deacetylase inhibitor (HDACi) was a milestone in the treatment of refractory T-cell lymphoma. However, the beneficial effects of HDACi have not been appreciated in osteoarthritis (OA). Herein, we implemented a microcarrier system because of the outstanding advantages of controlled and sustained release, biodegradability, and biocompatibility. The poly(d,l-lactide-co-glycolide) (PLGA) microcapsules have a regulated and sustained release profile with a reduced initial burst release, which can improve the encapsulation efficiency of the Chidamide. The emulsion solvent evaporation strategy was used to encapsulate Chidamide in PLGA microcapsules. The encapsulation of Chidamide was established by UV-vis spectra and scanning electron microscopy. Additionally, the inhibition of Tnnt3 and immune stimulation by Chidamide helped to inhibit cartilage destruction and prevent articular cartilage degeneration. Based on the results, the Chidamide in PLGA microcapsules provides a transformative therapeutic strategy for the treatment of osteoarthritis patients to relieve symptoms and protect against cartilage degeneration.
| S-EPMC10722529 | biostudies-literature
Project description:Osteoarthritis (OA) is a progressive and degenerative disease, which is no longer confined to the elderly. So far, current treatments are limited to symptom relief, and no valid OA disease-modifying drugs are available. Additionally, OA relative joint is challenging for drug delivery, since the drugs experience rapid clearance in joint, showing a poor bioavailability. Existing therapeutic drugs, like non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, are not conducive for long-term use due to adverse effects. Though supplementations, including chondroitin sulfate and glucosamine, have shown beneficial effects on joint tissues in OA, their therapeutic use is still debatable. New emerging agents, like Kartogenin (KGN) and Interleukin-1 receptor antagonist (IL-1 ra), without a proper formulation, still will not work. Therefore, it is urgent to establish a suitable and efficient drug delivery system for OA therapy. In this review, we pay attention to various types of drug delivery systems and potential therapeutic drugs that may escalate OA treatments.
| S-EPMC6758706 | biostudies-literature
Project description:ObjectiveQuercetin (Que), a bioflavonoid, is both anti-inflammatory and antioxidative. Que has been used as an oral supplement for osteoarthritis (OA) with inconsistent findings because of its low bioavailability. We encapsulated Que in a mPEG-polypeptide thermogel to prolong its bioactivity. The efficacy of this formulation was evaluated in a posttraumatic OA rat model.DesignMethoxy-poly(ethylene glycol)-l-poly(alanine) (mPEG-PA) polymer was synthesized and characterized in terms of cytotoxicity and release kinetics in vitro. At 12 weeks old, Sprague-Dawley rats underwent anterior cruciate ligament transection (ACLT). At 24 weeks post-operation, rats received either an intra-articular (IA) injection of saline, hydrogel, or hydrogel with Que (50 or 500 μg). Gait analysis was performed at pre-ACLT, pre-treatment, and at 4, 8, and 12 weeks post-treatment. At 12 weeks post-treatment, knee joints were collected for histopathological evaluation.ResultsIn vitro studies showed that chondrocytes were viable after 72 hours of incubation with mPEG-PA, and the release of Que could be sustained for >28 days. Among all OA rats, the limb idleness index (LII) were significantly increased at 24 weeks post-ACLT. Rats that received hydrogel with Que (50 μg) showed the most reduction in LII at both 4 and 8 weeks post-treatment. The Osteoarthritis Research Society International score of rats received hydrogel with Que (50 μg) was significantly lower than the control group. All rats suffered from low-grade synovitis (Krenn score: 2-4).ConclusionThis study suggests that a sustained delivery of Que (50 μg) could provide symptom relief and also delay the progression of OA in the knee.
| S-EPMC7488941 | biostudies-literature
Project description:Despite four decades of research in intra-articular drug delivery systems (DDS) and two decades of advances in disease-modifying osteoarthritis drugs (DMOADs), there is still no clinically available disease-modifying therapy for osteoarthritis (OA). Multiple barriers compromise intra-articular DMOAD delivery. Although multiple exciting approaches have been developed to overcome these barriers, there are still outstanding questions. We make several recommendations that can help in fully overcoming these barriers. Considering OA heterogeneity, we also propose a patient-centered, bottom-up workflow to guide preclinical development of DDS-based intra-articular DMOAD therapies. Overall, we expect this review to inspire paradigm-shifting innovations for developing next-generation DDS that can enable clinical translation of intra-articular DMOADs.
| S-EPMC8840969 | biostudies-literature
Project description:Drug delivery for osteoarthritis (OA) treatment is a continuous challenge because of their poor bioavailability and rapid clearance in joints. Intra-articular (IA) drug delivery is a common strategy and its therapeutic effects depend mainly on the efficacy of the drug-delivery system used for OA therapy. Different types of IA drug-delivery systems, such as microspheres, nanoparticles, and hydrogels, have been rapidly developed over the past decade to improve their therapeutic effects. With the continuous advancement in OA mechanism research, new drugs targeting specific cell/signaling pathways in OA are rapidly evolving and effective drug delivery is critical for treating OA. In this review, recent advances in various IA drug-delivery systems for OA treatment, OA targeted strategies, and related signaling pathways in OA treatment are summarized and analyzed based on current publications.
| S-EPMC9081192 | biostudies-literature
Project description:Intra-articular hip injection is a frequently used technique for diagnostic and therapeutic purposes and is gaining more importance for the early diagnosis of hip disease. It is commonly performed with imaging guidance such as ultrasonographic or fluoroscopic control. We describe our technique of injection of the hip using relative distances from anatomic surface landmarks, with the needle insertion point at the site of the proximal anterolateral portal for hip arthroscopy, with a posterior direction of 30° and targeted toward a junctional point between 2 perpendicular lines, 1 distal from the anterior superior iliac spine and the second anterior from the tip of the greater trochanter. This technique can be used without imaging guidance in the outpatient clinic. Moreover, it minimizes the need for radiographic exposure for more critical injections, such as the injection of contrast material before conducting magnetic resonance arthrogaphy of the hip.
| S-EPMC3716221 | biostudies-literature
Project description:BackgroundRecently, in an open pilot study, we found up to two years, a potential pain-relieving effect of intra-articular gold micro-particles using the patient's synovial fluid for patients with knee osteoarthritis (KOA). During the study the excluded group of patients, due to multisite pain, co-morbidities, and other exclusion criteria., received intra-articular gold micro-particles using hyaluronic acid,. We aimed to identify if pre-treatment characteristics influence the global outcome two years after intra-articular treatment for painful KOA with gold microparticles using hyaluronic acid.MethodsUsing hyaluronic acid as the carrier, 136 patients with KOA received intraarticular injections with 20 mg gold microparticles (72.000 particles, 20-40 μm in diameter). In the analysis, we included the Global Rating of Change Scale, Pain Detect Questionnaire (PDQ), Body Mass Index (BMI), and Kellgren & Lawrence score at the inclusion, Western Ontario, and McMaster Universities Osteoarthritis Index (WOMAC) sub-scores for pain, stiffness, and function at inclusion and two years.ResultsOn the Global Rating Change Scale, 69.1% of patients reported a positive effect, 28.7% no effect, and 2.2% worse. PDQ and the three WOMAC subscores all improved at two years of follow-up. PDQ ≥ 13 (P = 0.028), BMI (P = 0.022) and Kellgren & Lawrence grade 4 (P = 0.028) at inclusion reduced the effect with a minor odds ratio compared to the baseline effect of treatment (P = 0.025). WOMAC subscores at inclusion did not influence the outcome (P > 0.5).ConclusionsSevere osteoarthritis, obesity, and neuropathic pain, reduced the effect of intra-articular gold microparticles for knee OA.Trial registrationThe study followed the principles of the Declaration of Helsinki and was approved by the local ethics committee of the North Denmark Region by 27/07/2016 (N-20,160,045). The regional data protection agency approved the project by 06/07/2016 (2008-58-0028, ID 2016 - 116) and registered in ClinicalTrial.Gov by 04/01/2018 (NCT03389906).
| S-EPMC10935980 | biostudies-literature
Project description:Osteoarthritis (OA) is a degenerative disease of the joints and a leading cause of physical disability in adults. Intra-articular (IA) therapy is a popular treatment strategy for localized, single-joint OA; however, small-molecule drugs such as corticosteroids do not provide prolonged relief. One possible reason for their lack of efficacy is high clearance rates from the joint through constant lymphatic drainage of the synovial tissues and synovial fluid and also by their exchange via the synovial vasculature. Advanced drug delivery strategies for extended release of therapeutic agents in the joint space is a promising approach to improve outcomes for OA patients. Broadly, the basic principle behind this strategy is to encapsulate therapeutic agents in a polymeric drug delivery system (DDS) for diffusion- and/or degradation-controlled release, whereby degradation can occur by hydrolysis or tied to relevant microenvironmental cues such as pH, reactive oxygen species (ROS), and protease activity. In this review, we highlight the development of clinically tested IA therapies for OA and highlight recent systems which have been investigated preclinically. DDS strategies including hydrogels, liposomes, polymeric microparticles (MPs) and nanoparticles (NPs), drug conjugates, and combination systems are introduced and evaluated for clinical translational potential.
| S-EPMC7941755 | biostudies-literature