PURPOSE: The aim of this study was to develop and characterize a liposomal product containing @entity3446 to be administered subconjunctivally for the treatment of nonresponsive @entity9849 sicca (KCS) or @entity936 . METHODS: Formulations were prepared using an @entity1068 injection method and an adaptation of the heating method in pursuance of the most suitable methodology for future industrial production. Liposomes were loaded with either a high dose of 1   mg/mL of @entity3446 or a less toxic dose of 0.4   mg/mL. The effects of critical process and formulation parameters were investigated. Liposomes were characterized in terms of size, zeta potential, polydispersity, differential scanning calorimetry, morphology, entrapment efficiency, phospholipid content, thermal stability, and sterility. The formulation was evaluated clinically in @entity235 with spontaneous KCS. RESULTS: Sterile liposomal dispersions with sizes ranging from 140 to 211   nm, were successfully obtained. High entrapment efficiency of 93%-98% was achieved. The heating method allowed an easier production of liposomes with high entrapment efficiency, to significantly shorten production time and the elimination of the use of @entity285 . The poor stability of the obtained liposomes in aqueous dispersion made the inclusion of a lyophilization step necessary to the manufacturing process. In vivo testing of the liposomal @entity3446 formulations in the spontaneous KCS @entity235 model have produced promising results, particularly with a @entity3446 dose of 1   mg/mL, indicating the need for further development and study of proposed formulations in the treatment of @entity235 KCS. Clinical improvement in tear production in @entity235 with spontaneous KCS treated with the 1   mg/mL dose product was observed. CONCLUSIONS: The heating method allowed easier production of high entrapment efficiency liposomes to significantly shorten production time and the elimination of the use of @entity285 . Tear production was increased in @entity235 administered with the formulation.

Preformulation Studies of a Liposomal Formulation Containing XXXX for the Treatment of Dry Eye Disease.

@entity235 :: ('9615', 'Species') :: ['canine', 'dog', 'dogs'] @entity9849 :: ('MESH:D007637', 'Disease') :: ['keratoconjunctivitis'] @entity3446 :: ('MESH:D020123', 'Chemical') :: ['sirolimus'] @entity936 :: ('MESH:D015352', 'Disease') :: ['dry eye'] @entity285 :: ('D000431', 'Chemical') :: ['alcohol'] @entity1068 :: ('MESH:D000431', 'Chemical') :: ['ethanol']
@entity3446 :: (MESH:D020123,Chemical) :: ['Sirolimus']
