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

Abstract

Cornea is themajor 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 K_d 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 K_d 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 junctionmodulation 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.

Keywords

aptamers / cornea / tissue-SELEX

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