Abstract
Selectively targeted nanoscale drug delivery systems have recently emerged as promising intravenously therapeutic option for most chronic joint diseases. Here, a newly synthetized dodecapeptide (GE11)-polylactide-co-glycolide (PLGA)-based conjugate was used to prepare smart nanoparticles (NPs) intended for intra-articular administration and for selectively targeting Epidermal Growth Factor Receptor (EGFR). GE11-PLGA conjugate-based NPs are specifically uptaken by EGFR-overexpressed fibroblast; such as synoviocytes; which are the primarily cellular component involved in the development of destructive joint inflammation. The selective uptake could help to tune drug effectiveness in joints and to decrease local and systemic side effects. Dexamethasone (DXM) is a glucorticoid drug commonly used in joint disease treatment for both systemic and local administration route. In the present research; DXM was efficiently loaded into GE11-PLGA conjugate-based NPs through an eco-friendly nanoprecipitation method set up for this purpose. DXM loaded GE11-PLGA conjugate-based NPs revealed satisfactory ex vivo cytocompatibility; with proper size (≤150 nm) and good dimensional stability in synovial fluid. Intra-articular formulation was developed embedding DXM loaded GE11-PLGA conjugate-based NPs into thermosetting chitosan-based hydrogel; forming a biocompatible composite hydrogel able to quickly turn from liquid state into gel state at physiological temperature; within 15 min. Moreover; the use of thermosetting chitosan-based hydrogel extends the local release of active agent; DXM.
Highlights
Corticosteroid intra-articular (IA) injection is a long-established treatment for patients with chronic and non-curable joint diseases, such as rheumatoid arthritis (RA) and most different arthritis-related forms [1,2,3,4]. chronic joint diseases differ in etiology and relative risk factors, symptoms, prognoses, and treatments, growing numbers of systemic administered drugs can be employed to manage, alone or in combination, the joint disorders [5]
The highest drug loading (230 μg/100 mg polymer) was obtained using 100 mg of PLGA (75:25 relative lactide:glycolide composition) in a mixture of acetone-dichloromethane at ratio 1:1 (v:v) and using 10 mg of initial DXM. Starting from these considerations and from results published in our previous work [28,31], DXM loaded GE11-PLGA/PEG-PLGA blend NPs were prepared using a 1:10 weight ratio of DXM respect to the polymer matrix which is composed by 1:1 ratio (w:w) blending of GE11-PLGA and PEG-PLGA
PLGA was characterized by 75:25 relative lactide:glycolide composition
Summary
Corticosteroid intra-articular (IA) injection is a long-established treatment for patients with chronic and non-curable joint diseases, such as rheumatoid arthritis (RA) and most different arthritis-related forms (i.e., osteoarthritis, a chronic RA-like inflammatory arthritis, post-traumatic arthritis or osteoarthritis, and pseudo gout, an acutely painful inflammatory condition) [1,2,3,4]. chronic joint diseases differ in etiology and relative risk factors, symptoms, prognoses, and treatments, growing numbers of systemic administered drugs can be employed to manage, alone or in combination, the joint disorders [5]. Corticosteroid intra-articular (IA) injection is a long-established treatment for patients with chronic and non-curable joint diseases, such as rheumatoid arthritis (RA) and most different arthritis-related forms (i.e., osteoarthritis, a chronic RA-like inflammatory arthritis, post-traumatic arthritis or osteoarthritis, and pseudo gout, an acutely painful inflammatory condition) [1,2,3,4]. Since the poor efficacy of systemic treatments in chronic joint diseases is primarily due to the low drug availability within articular joints, IA administration could offer an interesting therapeutic strategy to increase drug concentration at the site of action, minimizing overall systemic exposure [4,12]. The reduced retention time of therapeutic agents in the targeted tissue requires frequent injections, which are associated with both risk of infection and/or joint disability and unsatisfactory patient compliance [4]. Repeated IA administrations of GCs could cause permanent damages to the articular cartilage, and systemic adverse events cannot be fully avoided; precautions should be observed in patients with concomitant diseases such as hypertension or diabetes mellitus [5,15]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
