Injectable Thermoresponsive Hydrogels Modified Utilizing Novel Non-Covalent Complexation Strategies for Sustained Release of 3DNA Nanocarriers.

Authors

Camila Vardar, Giavanna Trojan, Mark E Byrne

Published in

Journal of biomedical materials research. Part B, Applied biomaterials. Volume 114. Issue 11.

Abstract

This work demonstrates, for the first time, the development of novel injectable, self-assembling hydrogels using biomimetic complexation strategies to control and sustain the release of antibody-targeted DNA-based nanocarriers designed to specifically target and deplete the cells responsible for the onset of posterior capsule opacification (PCO). Naturally occurring charged homopolymers were incorporated into poly(d,l-lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(d,l-lactic-co-glycolic acid) (PLGA-PEG-PLGA) matrices to further control and extend release of 3DNA nanocarriers through electrostatic interactions. Injectable, thermosensitive gels were developed using PLGA-PEG-PLGA triblock copolymer, poly-l-lysine, and hyaluronic acid at different concentrations and molecular weights for the sustained release of targeted nucleic acid nanocarriers loaded with cytotoxic doxorubicin (G8:3DNA:Dox). Characterization studies included optical clarity, critical gelation temperature (GT), and sustained drug release kinetics. The formulations showed great specificity for myofibroblast precursors with minimal off-target effects. Hydrogels are in situ forming, nontoxic, and optically clear at 37°C, and therefore can be irrigated over the lens capsule at the time of surgery. Modification with charged homopolymers extended release from 1 up to 5 months. Our findings from ex vivo studies show that extending delivery of a low dose of DNA-based nanocarriers by exploiting long-chain non-covalent interactions led to targeted depletion of myofibroblasts and progenitor cells below levels that do not cause wrinkling or visual abnormalities. This system has the potential to be used with every cataract surgery patient and decrease the incidence of PCO and associated complications. Moreover, this gel can be adapted to deliver various other types of therapeutics into the eye.

PMID:
43023656
Bibliographic data and abstract were imported from PubMed on 13 Nov 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.