Preparation and in vitro-in vivo evaluation of solid lipid nanoparticle, microemulsion and polymeric nanoparticle formulations containing cyclosporine A

Cyclosporine A (CsA) is applied topically in the therapy of disorders after corneal transplantation and dry eye syndrome. Systemic absorption of CsA is quite low and there is inter-individual variation in plasma concentrations depending on the dosage form applied and the story of the patient. Therefore, in this study, solid lipid nanoparticle (SLN), microemulsion (ME) and polymeric nanoparticle (PN) formulations were prepared aiming the ocular delivery of CsA with an attempt to decrease the inter-individual variation through increasing the topical absorption. In the stability studies, behaviours of the formulations prepared were investigated at different conditions. Particle and globule sizes of the formulations remained in the nanometer range during the stability studies. Positively charged zeta potentials obtained with the addition of cationic lipid remained unchanged showing the stability of the formulations. Lipid strucrures of SLNs were verified to be unchanged by the X-ray diffraction (XRD), infrared (IR) and nuclear magnetic resonance (NMR) analyses. Three formulations among the three different systems were selected for the in vivo studies considering the stability test results. In the in vivo studies carried on the sheep, formulations were applied topically to the one of the eye and the other eye remained untreated as a reference. At appropriate time intervals, sheep were sacrificed and the aqueous and vitreous humour samples of the eyes were collected and analysed by enzyme immune assay (EIA) analyzer. Ocular absorption of CsA was evaluated according to the EIA results of the CsA samples obtained previously. According to the in vivo analysis results, CsA was determined in the aqueous and vitreous humour samples in 48 hours. Detection of CsA in the vitreous humour showed the efficient absorption of the drug to the deeper layers of the eye. Similarity of the analysis results demonstrated that inter-individual variance did not affect the absorption level. Key Words : Cyclosporine A, ocular absorption, aqueous humour, vitreous humour