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

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), fo...

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Bibliographic Details
Published in:Drug delivery 2022-12, Vol.29 (1), p.489-498
Main Authors: Ji, Han Bi, Hong, Jae Young, Kim, Cho Rim, Min, Chang Hee, Han, Jae Hoon, Kim, Min Ji, Kim, Se-Na, Lee, Cheol, Choy, Young Bin
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents, Non-Steroidal - administration & dosage
Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Bioengineering
Cell Survival - drug effects
Chemistry, Pharmaceutical
Controlled drug delivery
Delayed-Action Preparations
diclofenac
Diclofenac - administration & dosage
Diclofenac - pharmacokinetics
Diclofenac - pharmacology
Drug dosages
Drug Implants - chemistry
Drug Liberation
fibrosis
Fibrosis - pathology
implantable device
Lasers
microchannel
Nonsteroidal anti-inflammatory drugs
ortho-Aminobenzoates - administration & dosage
ortho-Aminobenzoates - pharmacokinetics
ortho-Aminobenzoates - pharmacology
Polyethylene glycol
Polymers
Rats
Rats, Sprague-Dawley
Transplants & implants
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Summary: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.
ISSN:1071-7544
1521-0464
DOI:10.1080/10717544.2022.2032873