Injectable cell-encapsulating composite alginate-collagen platform with inducible termination switch for safer ocular drug delivery

Biomaterials
Francisca S Y WongAmy C Y Lo

Abstract

Effective retinal drug delivery remains a challenge for treating vision-threatening diseases. Encapsulated-cell therapy (ECT) can provide local drug delivery without repeated invasive injections but is plagued by unsteady performance and biosafety issues. Here, an injectable composite alginate-collagen (CAC) ECT gel with a Tet-on inducible pro-caspase 8 mechanism that acted as an orally-inducible biosafety switch was developed for safer drug delivery. The optimised gels (2 mg/ml collagen, 1.5% high molecular weight alginate and 50,000 cells/gel) could be effectively terminated in vitro (≥20 pg/ml Doxycycline) and in vivo (1 mg/ml oral Doxycycline after 48 h). Also, they displayed effective proliferation control and continuous delivery of bioactive glial-cell derived neurotrophic factor (GDNF) with no significant gel degradation in vitro and in rat vitreous. Most importantly, intravitreally injected gels demonstrated therapeutic efficacy in Royal College of Surgeons rats with degenerating retina in reducing photoreceptor apoptosis and retina function loss. Furthermore, double gel injections into the same eye yielded better outcomes without compromising gel viability. Retrieved gels showed no host-tissue attachment or cell-protru...Continue Reading

Citations

Mar 27, 2020·Journal of Biomaterials Science. Polymer Edition·Naoya KinoshitaKazunari Akiyoshi
May 11, 2019·The Journal of Pharmacology and Experimental Therapeutics·Vrinda GoteDhananjay Pal
Dec 17, 2020·Materials·Ruxandra-Elena Geanaliu-Nicolae, Ecaterina Andronescu
Dec 20, 2020·Bioengineering·Vaidehi A Patil, Kristyn S Masters
Jun 12, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Tania B Lopez-MendezRosa Maria Hernandez
Jul 20, 2021·ACS Biomaterials Science & Engineering·Sung-Min KangShuichi Takayama
Aug 8, 2021·Materials·Melitini KoutsovitiMarilena Vlachou

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

© 2022 Meta ULC. All rights reserved