Cornea-SELEX for aptamers targeting the surface of eyes and liposomal drug delivery

Using pig cornea as a target, aptamers were selected using the tissue-SELEX method. By attaching the aptamers to liposomes loaded with cyclosporin A, improved treatment of dry eye disease was achieved in vitro and in vivo.

Abstract:

Cornea is the major barrier to drug delivery to the eye, which results in low bioavailability and poor efficacy of topical eye treatment. In this work, we first select cornea-binding aptamers using tissue-SELEX on pig cornea. The top two abundant aptamers, Cornea-S1 and Cornea-S2, could bind to pig cornea, and their Kd values to human corneal epithelial cells (HCECs) were 361 and 174 nм, respectively. Aptamer-functionalized liposomes loaded with cyclosporine A (CsA) were developed as a treatment for dry eye diseases. The Kd of Cornea-S1- or Cornea-S2-functionalized liposomes reduces to 1.2 and 15.1 nм, respectively, due to polyvalent binding. In HCECs, Cornea-S1 or Cornea-S2 enhanced liposome uptake within 15 min and extended retention to 24 h. Aptamer CsA liposomes achieved similar anti-inflammatory and tight junction modulation effects with ten times less CsA than a free drug. In a rabbit dry eye disease model, Cornea-S1 CsA liposomes demonstrated equivalence in sustaining corneal integrity and tear break-up time when compared to commercial CsA eye drops while utilizing a lower dosage of CsA. The aptamers obtained from cornea-SELEX can serve as a general ligand for ocular drug delivery, suggesting a promising avenue for the treatment of various eye diseases and even other diseases.

Author list:

Ka-Ying Wong, Yibo Liu, Man-Sau Wong, Juewen Liu*

How to cite:

K.-Y. Wong, Y. Liu, M.-S. Wong, J. Liu, Exploration 2024, 20230008.
https://doi.org/10.1002/EXP.20230008