A novel penetratin-modified complex for noninvasive intraocular delivery of antisense oligonucleotides

Publication date: 30 August 2017 Source:International Journal of Pharmaceutics, Volume 529, Issues 1–2 Author(s): Lingyu Tai, Chang Liu, Kuan Jiang, Xishan Chen, Linglin Feng, Weisan Pan, Gang Wei, Weiyue Lu Inhibition of gene expression by nucleic acids is a promising strategy in the treatment of ocular diseases. However, intraocular delivery of nucleic acids to the posterior ocular tissues remains a great challenge due to the presence of various biological barriers. To circumvent this problem, we established a novel penetratin (P) modified poly(amidoamine) dendrimer (D)/hyaluronic acid (H) complex to deliver antisense oligonucleotides (ASOs, O). Complexes (D/O, HD/O and PHD/O) were easily prepared and modification layers (hyaluronic acid and penetratin) were respectively absorbed on the surface via electrostatic interaction. Complexes with different outer layers were characterized as spherical particles with reversed charges. In vitro cellular uptake of ASOs in PHD/O complex was significantly increased than those in other formulations. In vivo studies were carried out after topical instillation of the complexes in the conjunctival sac of mice. Compared with D/O and HD/O, PHD/O exhibited much more distribution in the posterior segment of the eyes and prolonged retention time of ASOs in retina for more than 8h. Taken together, these results indicated that PHD/O complex possessed substantially improved ocular permeability and distribution in the posterior ocular ti...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research