Novel Atorvastatin loaded peptide amphiphiles for corneal neovascularization

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-Tat_47-57, dC₁₆-Tat_47-57 and qC₁₆-Tat_47-57) were synthesized using solid-phase synthesis, characterized physically and morphologically and loaded with ATV. From them, ATV-qC₁₆-Tat_47-57 showed higher encapsulation efficiency than mC₁₆-Tat_47-57 and dC₁₆-Tat_47-57 and more defined nanostructures with a tubular shape. Moreover, in vitro ATV release was also assessed confirming that ATV-qC₁₆-Tat_47-57 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-Tat_47-57 confirmed that ATV-qC₁₆-Tat_47-57 were not irritant. Moreover, ATV-qC₁₆-Tat_47-57 demonstrated to be antiangiogenic in an in ovo model and was able to prevented ocular inflammation in vivo.

Therefore, ATV-qC₁₆-Tat_47-57 constitutes a promising topical medication against corneal neovascularization.