Replenishable drug depot to combat post-resection cancer recurrence

Abstract

Local drug presentation made possible by drug-eluting depots has demonstrated benefits in a vast array of diseases, including in cancer, microbial infection and in wound healing. However, locally-eluting depots are single-use systems that cannot be refilled or reused after implantation at inaccessible sites, limiting their clinical utility. New strategies to noninvasively refill drug-eluting depots could dramatically enhance their clinical use. In this report we present a refillable hydrogel depot system based on bioorthogonal click chemistry. The click-modified hydrogel depots capture prodrug refills from the blood and subsequently release active drugs locally in a sustained manner. Capture of the systemically-administered refills serves as an efficient and non-toxic method to repeatedly refill depots. Refillable depots in combination with prodrug refills achieve sustained release at precancerous tumor sites to improve cancer therapy while eliminating systemic side effects. The ability to target tissues without enhanced permeability could allow the use of refillable depots in cancer and many other medical applications.

Multifaceted Design and Emerging Applications of Tissue Adhesives

“…[ 134 ] It could also be refilled to achieve sustained drug eluting. [ 361 ] This approach can overcome the limitations of conventional drug administration such as low efficacy, high dosage, and poor targeting. [ 13 ] Additionally, stem cells (such as human MSCs) could be hosted in hydrogel adhesives with fine‐tuned chemical and physical properties before differentiating and/or migrating to targeted tissues.…”

Transmitter and Receiver Architectures for Molecular Communications: A Survey on Physical Design With Modulation, Coding, and Detection Techniques

“…The E-field stimuli can be generated by two electrodes placed at the opposite walls of the reservoir. Refilling the IM reservoirs is another significant challenge in the MC-Tx design, which can be solved with the replenishable drug delivery methods, e.g., oligodeoxynucleotides (ODN) modification [81], click chemistry [82], and refill lines [83]. In this way, the utilization of hydrogels further enhances in-body MC applications by extending the device lifetimes via molecule uptake mechanisms.…”

Hitchhiking on Controlled-Release Drug Delivery Systems: Opportunities and Challenges for Cancer Vaccines

“…Furthermore, many dual-sensitive hydrogels have gained enormous attention in more precisely controlling the release profiles of drugs, such as thermo-pH dual-sensitive hydrogels ( Liu et al, 2019a ), thermo-reactive oxygen species (ROS) dual-sensitive hydrogels ( Yu et al, 2018 ) and electric field-pH double-sensitive hydrogels ( Qu et al, 2018 ). Interestingly, Brudno et al developed a replenishable and injectable hydrogel depot system which could capture systemically administrated prodrug refills and then release them locally in a sustained manner ( Brudno et al, 2018 ). This repeatedly refillable hydrogel can be used to prepare precisely controlled-release or pulsatile-release cancer vaccines.…”