Soft implantable device with drug-diffusion channels for the controlled release of diclofenac

Microchannel-embedded implantable device with fibrosis suppression for prolonged controlled drug delivery

“…The DF herein was proposed to be systemically exposed, and thus, we pursued the dose to be sufficiently high so that the in vivo concentration of the DF in the blood plasma could be measurable via HPLC/MS, as described above. For subcutaneously implanted devices in a previous study (Ji et al., 2020 ), a daily DF dose of over 180 μg/day was seen to be detectable using the current animal model and assay method. According to the results in Figure 2(B) , two pairs of a 3-mm microchannel and reservoir could meet this dose; thus, we again prepared these two pairs in a single DDC to produce a DF_DDC_3(x2) ( Figure 3(C) ).…”

“…In this work, we assessed this strategy using a DDC embedded with microchannels as an example of a nondegradable, implantable device for precise drug delivery. We utilized the channels in millimeter length to achieve both relatively rapid onset and sustained drug release according to our previous reports (Lee et al., 2014 ; Ji et al., 2020 ). Our findings revealed that the microchannels could modulate the release pattern of each drug in a controlled manner, depending on their dimensions ( Figure 2 ).…”

“…To examine the cell compatibility, a DDC without drug loading was utilized to perform an indirect cytotoxicity test (Jeong et al., 2018 ; Ji et al., 2020 ). For this, we used L929 mouse fibroblast cells (KLCB, Republic of Korea) grown in an RPMI 1640 medium supplemented with 10% fetal bovine serum, 100 units/ml penicillin, and 100 μg/ml of streptomycin.…”

“…For the TR, the measurement conditions were the same as those described above for the in vitro drug release study. For the DF analysis, the mobile phase was composed of methanol and 10 mM ammonium acetate (70:30, v/v) (Ji et al., 2020 ). The flow rate and injection volume were set at 0.5 ml/min and 10 μl, respectively.…”

“…However, when the devices are implanted in a living body, an inevitable foreign body reaction causes a fibrotic capsule formation around the device, and this additional barrier hampers systemic drug absorption, as reported for many other implantable devices (Bank, 2019 ; Asrory et al., 2020 ). This has been considered problematic, as the fibrotic capsule often greatly lowers systemic drug exposure, even for a device with a highly controlled drug release (Ji et al., 2020 ).…”