Please login first
Novel Atorvastatin loaded peptide amphiphiles for corneal neovascularization
* 1, 2, 3 , 1 , 1
1  Unit of Synthesis & Biomedical Applications of Peptides, IQAC-CSIC, 08034, Barcelona, Spain
2  Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028, Barcelona, Spain
3  Institute of Nanoscience & Nanotechnology (IN2UB), University of Barcelona, 08028, Barcelona, Spain
Academic Editor: Alfredo Berzal-Herranz (registering DOI)

Corneal neovascularization constitutes a serious sight-threatening disease. This pathology can be treated using antiangiogenic and anti-inflammatory compounds. Therefore, in this area, atorvastatin (ATV) constitutes a suitable candidate to be administered topically to the eyes due to its pharmacological properties. However, ATV possess low water solubility and it is rapidly eliminated in traditional formulations. Therefore, to attain suitable efficacy, ATV has been encapsulated into custom-developed peptide amphiphiles.

In this study, three peptide amphiphiles bearing one, two or four C16-alkyl groups (mC16-Tat47-57, dC16-Tat47-57 and qC16-Tat47-57) were synthesized using solid-phase synthesis, characterized physically and morphologically and loaded with ATV. From them, ATV-qC16-Tat47-57 showed higher encapsulation efficiency than mC16-Tat47-57 and dC16-Tat47-57 and more defined nanostructures with a tubular shape. Moreover, in vitro ATV release was also assessed confirming that ATV-qC16-Tat47-57 showed ATV prolonged release. In vitro (HEM-CAM and CAM-TBS) and in vivo ocular tolerance (Draize test in New Zealand rabbits) of ATV-qC16-Tat47-57 confirmed that ATV-qC16-Tat47-57 were not irritant. Moreover, ATV-qC16-Tat47-57 demonstrated to be antiangiogenic in an in ovo model and was able to prevented ocular inflammation in vivo.

Therefore, ATV-qC16-Tat47-57 constitutes a promising topical medication against corneal neovascularization.

Keywords: atorvastatin; angiogenesis; drug delivery; ocular inflammation; peptide amphiphiles