具有药物扩散通道的软植入式双氯芬酸控释装置

Abstract(#br)We propose the use of an implantable device with multiple embedded drug diffusion channels, each of which is connected to a drug reservoir, for the controlled release of diclofenac. To minimize the size of the incision needed during device implantation, the device used herein was made of the soft biocompatible material polydimethylsiloxane (PDMS), thereby allowing for folding during device implantation. We aimed to achieve a profile of diclofenac release that was reproducible even after folding, and thus the channel was filled with cross-linked gelatin, which could be swollen via the infiltration of a bodily fluid to compensate for any possible defects formed during folding. We first assessed the use of individual channels of varying lengths of 1–12 mm, and the onset time and average rate varied from 1 to 14 days and from 0.31–4.3%/day, respectively. According to these results, we prepared a device with multiple integrated pairs of drug reservoirs and channels of different lengths (i.e., the SDD_I), in which the channel combination was selected to achieve the long-term, zero-order release of the largest amount of drug. Thus, the SDD_I used herein exhibited almost zero-order drug release for 55 days at a release rate of 1.19%/day (179.8 μg/day), which did not vary even after the device was folded multiple times due to the presence of gelatin in the channel. When tested in living rats, the SDD_I device could be folded and inserted subcutaneously through an incision less than half the size of that needed for the implantation of the unfolded, intact SDD_I. For both the unfolded and folded SDD_I devices, the drug concentration in blood was observed to be maintained within a similar range due to the almost zero-order, reproducible release of diclofenac.