Synthesis, characterizations,in vitroandin vivoevaluation of Etoricoxib-loaded Poly (Caprolactone) microparticles – a potential Intra-articular drug delivery system for the treatment of Osteoarthritis

Abstract

Intra-articular Drug delivery systems (IA-DDS) deliver the drug directly to the diseased joint space with significantly lowered systemic toxicities. In this work, we explored Etoricoxib (COX-2 inhibitor)-loaded Poly caprolactone (PCL) microparticles (MPs) as a potential IA-DDS. MPs were prepared by Oil/Water (O/W) emulsion-solvent evaporation method. Formulation parameters like polymer to drug ratio, stabilizer concentration were optimized to get the maximum encapsulation efficiency. The prepared particles were characterized using Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction studies (XRD), and Differential Scanning Calorimetry (DSC). The particles were found to be spherical and smooth-surfaced using SEM. FTIR studies proved that there was no chemical interaction between the drug and the polymer. XRD and DSC studies confirmed that Etoricoxib existed in its amorphous form while PCL had retained its semi-crystalline phase during the micro-encapsulation process. In vitro drug release studies proved that there was controlled release of the drug from the MPs for nearly 28 days. In vivo synovial drug clearance studies on SD rats proved that drug leach out rate from the joint region to the systemic circulation was slow which indicated that MPs had a good drug retention capacity. In vivo fluorescence imaging results confirmed that MPs could stay longer in the joint region for almost a month. Thus, PCL microparticles could be a potential IA-DDS for the treatment of the diseased joint regions especially for Osteoarthritis.

Thermo- and pH-dual responsive polymeric micelles with upper critical solution temperature behavior for photoacoustic imaging-guided synergistic chemo-photothermal therapy against subcutaneous and metastatic breast tumors

“…Additionally, the characteristic peaks of DOX and IR780 did not present in the XRD spectrum of mPEG-PAAV micelles/IR780+DOX as shown in Figure S7 , indicating that DOX and IR780 were successfully encapsulated in mPEG-PAAV micelles in their amorphous form. Previous studies have demonstrated that when drugs are encapsulated into the particle in their amorphous form, they lose their crystallinity 29 , 30 .…”

Biomaterial strategies for improved intra‐articular drug delivery

“…The use of larger particles that could better avoid lymphatic drainage and cell‐mediated particles elimination (Figure 1) is a potential strategy to achieve IA drug sustained release over longer periods of time. In fact, polycaprolactone (PCL) microparticles with an average size of 16 μm were found to remain in the joint space of rats for up to a month 79 . Janssen et al synthesized celecoxib‐loaded polyester amide (PEA) microspheres with a mean particle size of 25 μm and were able to detect around 20% of the injected PEA 12 weeks after IA injection in Lewis rats 80 .…”

Biomaterial-engineered intra-articular drug delivery systems for osteoarthritis therapy

“…investigated the potential of polycaprolactone (PCL) microparticles to deliver drugs for OA (Arunkumar et al. 2016b). As in vivo results showed, the drug was slowly released, and the whole microparticles were still detected in the joint after one month.…”