In vitro and in vivo delivery of the secretagogue diadenosine tetraphosphate from conventional and silicone hydrogel soft contact lenses

Abstract

PurposeTo evaluate the possible use of soft contact lenses (CL) to improve the secretagogue role of diadenosine tetraphosphate (Ap4A) promoting tear secretion. MethodsTwo conventional hydrogel CL (Omafilcon A and Ocufilcon D) and two silicone hydrogel (SiH) CL (Comfilcon A and Balafilcon A) were used. Ap4A was loaded into the lenses by soaking in a 1mM Ap4A solution during 12h. In vitro experiments were performed by placing the lenses in multi-wells during 2h containing 1ml of ultrapure water. 100μl aliquots were taken at time zero and every minute for the first 10min, and then every 15min. In vivo experiments were performed in New Zealand rabbits and both the dinucleotide release from SiH and tear secretion were measured by means of Schirmer strips and high-pressure liquid chromatography (HPLC) analysis. ResultsAp4A in vitro release experiments in hydrogel CL presented a release time 50 (RT50) of 3.9±0.2min and 3.1±0.1min for the non-ionic and the ionic CL, respectively. SiH CL released also Ap4A with RT50 values of 5.1±0.1min for the non-ionic and 2.7±0.1min for the ionic CL. In vivo experiments with SiH CL showed RT50 values of 9.3±0.2min and 8.5±0.2min for the non-ionic and the ionic respectively. The non-ionic lens Ap4A release was able to induce tear secretion above baseline tear levels for almost 360min. ConclusionThe delivery of Ap4A is slower and the effect lasts longer with non-ionic lenses than ionic lenses.