Chitosan/Pluronic F127 Thermosensitive Hydrogel as an Injectable Dexamethasone Delivery Carrier

Abstract

Intra-articular administration of anti-inflammatory drugs is a strategy that allows localized action on damaged articular cartilage and reduces the side effects associated with systemic drug administration. The objective of this work is to prepare injectable thermosensitive hydrogels for the long-term application of dexamethasone. The hydrogels were prepared by mixing chitosan (CS) and Pluronic-F127 (PF) physically. In addition, tripolyphosphate (TPP) was used as a crosslinking agent. Chitosan added to the mix increased the gel time compared to the pluronic gel alone. The incorporation of TPP into the material modified the morphology of the hydrogels formed. Subsequently, MTS and Live/Dead® experiments were performed to investigate the toxicity of hydrogels against human chondrocytes. The in vitro releases of dexamethasone (DMT) from CS-PF and CS-PF-TPP gels had an initial burst and took more time than that from the PF hydrogel. In vivo studies showed that hydrogels retained the fluorescent compound longer in the joint than when administered in PBS alone. These results suggest that the CS-PF and CS-PF-TPP hydrogels loaded with DMT could be a promising drug delivery platform for the treatment of osteoarthritis.

Thermosensitive Injectable Hydrogels for Intra-Articular Delivery of Etanercept for the Treatment of Osteoarthritis

“…The cause of this result is the hydrophobic interactions of the PF molecules, conditioned by the interspersed chitosan chains. This results in a slight decrease in the micellar formation and packing, which is the main cause of PF gelation [ 27 , 28 , 29 ]. In the CS/PF/BGP hydrogel, the mentioned effect was counteracted by the addition of BGP, which favored chitosan gelling when increasing the temperature to 37 °C.…”

“…The chitosan/Pluronic (CS/PF) hydrogels were prepared following the previously established methodology [ 29 ]. Briefly, a solution of 1.2% ( w / v ) CS in 1% ( v / v ) acetic acid was prepared, the pH was adjusted to approximately 6.4 with NaOH 0.1 mol/L and allowed to cool down.…”

“…C28/I2 cells were grown in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% fetal bovine serum and 1% w/v antibiotics consisting of streptomycin (100 µg/mL) and penicillin (100 IU/mL). The assay was carried out using a procedure described elsewhere [ 29 ]. Briefly, 1 × 10 4 cells were seeded onto the freeze-dried hydrogels placed in 96-well plates, and cultured in a standard cell culture incubator with 5% CO 2 at 37 °C.…”

Intelligent Hydrogels in Myocardial Regeneration and Engineering

“…Pluronics ® F-127 is a synthetic polymer made up of units of ethylene oxide (PEO) and propylene oxide (PPO) with appreciable bio-adhesiveness and biocompatibility [ 27 ]. Pluronics ® F-127 has shown promising results in toxin neutralization, drug delivery, and cell delivery [ 28 , 29 , 30 , 31 ]. The hydrogel transitions from liquid to gel at the critical gelation temperature of 37 °C, at which micelles molecules self-assemble into a hard sphere crystallization structure through interactions of the hydrophilic chains of the copolymers [ 27 , 32 ].…”

Smart Injectable Chitosan Hydrogels Loaded with 5-Fluorouracil for the Treatment of Breast Cancer

“…Based on the above, the main objective of this work was the development of a thermosensitive hydrogel from the physical mixture of CS and Pluronic F 127/β-GP for the controlled release of 5-FU. Although this physical combination of polymers has been previously reported by others for intranasal [ 20 ], vaginal [ 21 ], intravesical [ 22 ], ocular [ 23 ], and injectable cell delivery carrier for cartilage regeneration [ 24 ], and intra-articular [ 25 ] delivery, there are no reports of its use for intra-tumoral application in breast cancer. In addition, chitosan/Pluronic gel beads were reported previously [ 26 ] and utilized for the release of 5-FU.…”