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

Abstract

For the prolonged, controlled delivery of systemic drugs, we propose an implantable drug-delivery chip (DDC) embedded with pairs of a microchannel and drug-reservoir serving as a drug diffusion barrier and depot, respectively. We pursued a DDC for dual drugs: a main-purpose drug, diclofenac (DF), for systemic exposure, and an antifibrotic drug, tranilast (TR), for local delivery. Thus, the problematic fibrotic tissue formation around the implanted device could be diminished, thereby less hindrance in systemic exposure of DF released from the DDC. First, we separately prepared DDCs for DF or TR delivery, and sought to find a proper microchannel length for a rapid onset and sustained pattern of drug release, as well as the required drug dose. Then, two distinct DDCs for DF and TR delivery, respectively, were assembled to produce a Dual_DDC for the concurrent delivery of DF and TR. When the Dual_DDC was implanted in living rats, the DF concentration in blood plasma did not drop significantly in the later periods after implantation relative to that in the early periods before fibrotic tissue formation. When the Dual_DDC was implanted without TR, there was a significant decrease in the blood plasma DF concentration as the time elapsed after implantation. Biopsied tissues around the Dual_DDC exhibited a significant decrease in the fibrotic capsule thickness and collagen density relative to the Dual_DDC without TR, owing to the effect of the local, sustained release of the TR.

An Ultrasoft and Flexible PDMS-Based Balloon-Type Implantable Device for Controlled Drug Delivery

“…In addition, the zero-order release time was slightly reduced in the in vivo environment, mainly due to fibrotic capsule formation, which is inevitable for many nondegradable implantable devices [ 50 , 51 ]. However, the zero-order release period achieved by our device was higher than that of previously developed devices [ 11 , 12 , 47 ], mainly due to the device compatibility with biological tissues and delayed fibroblast encapsulation, which resulted in prolonged zero-order release in the in vivo environment.…”

“…Although the device was made of soft materials using molding techniques, the device was relatively hard and rigid due to the thickness of the device, which resulted in high foreign body responses with a minimum capsule thickness of 858.818 ± 52.6 μm. Conversely, rigid-type devices, including micro-chips embedded with micro-channels, were also used to achieve almost zero-order release [ 12 , 47 ]. These micro-chips were fabricated using rigid materials, resulting in severe foreign body responses with a fibrotic capsule thickness ranging from 903.9 ± 48.91 to 990.9 ± 111.5 μm.…”

“…The degree of inflammation around the USBD was assessed to be minimal and noticeably less than that of previously developed devices [ 11 , 12 , 47 , 52 ]. Ji et al.…”

Fe-Porphyrin Cross-Linked Hydrogel for Reactive Oxygen Species Scavenging and Oxygen Generation in Diabetic Wounds

“…Cell viability (%) = (absorbance at 450 nm of the treated well − absorbance at 600 nm of the treated well)/(absorbance at 450 nm of the untreated control well − absorbance at 600 nm of the untreated control well) × 100. 28 2.6. In Vitro Efficacy Evaluation.…”

Gold Nanoparticles as Drug Carriers: The Role of Silica and PEG as Surface Coatings in Optimizing Drug Loading

“…Drug delivery systems are designed to deliver therapeutic agents in order to maximize their effectiveness and minimize their side effects [ 1 ]. There are many different types of drug delivery systems, including micro- [ 2 ] and nanoparticles [ 3 ], nanoplatforms [ 4 , 5 , 6 ], devices [ 7 , 8 , 9 , 10 ], and theragnostic platforms [ 11 , 12 , 13 ]. These systems can be used to deliver a wide range of drugs, including chemotherapeutics [ 14 , 15 , 16 ], gene therapies [ 17 , 18 , 19 , 20 ], and other biologics [ 21 , 22 , 23 , 24 , 25 , 26 ].…”