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

PURPOSE: The aim of this study was to develop and characterize a liposomal product containing sirolimus to be administered subconjunctivally for the treatment of nonresponsive keratoconjunctivitis sicca (KCS) or dry eye. METHODS: Formulations were prepared using an ethanol 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 sirolimus 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 dogs 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 alcohol. 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 sirolimus formulations in the spontaneous KCS dog model have produced promising results, particularly with a sirolimus dose of 1 mg/mL, indicating the need for further development and study of proposed formulations in the treatment of canine KCS. Clinical improvement in tear production in dogs 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 alcohol. Tear production was increased in dogs administered with the formulation.

Endoftalmite bacteriana severa bilateral em cão após facectomia intracapsular - relato de caso / Bilateral bacterial endophthalmitis in dog after intracapsular surgery - case report / Endoftalmitis bacteriana grave bilateral en perro tras faquectomía intracapsular - relato do caso

A Endoftalmite é um processo inflamatório grave que acomete o interior do bulbo ocular, podendo levar à cegueira e até mesmo à enucleação. Vários micro-organismos estão envolvidos na sua etiopatogenia, tais como bactérias, vírus, protozoários e outros. Estes podem ser inoculados no olho após cirurgias oftálmicas, traumas não cirúrgicos ou mesmo por via hematógena decorrente de uma infecção sistêmica. O objetivo deste trabalho foi relatar um caso de endoftalmite bacteriana bilateral em um cão, apresentando hipópio severo, secreção purulenta e úlcera em melting. O diagnóstico microbiológico foi realizado por meio da cultura e antibiograma após enucleação bilateral.

Endophthalmitis is a severe inflammatory process that affects the eve, which can lead to blindness and even enucleation. Several microorganisms are involved in their pathogenesis, such as bacteria, viruses, protozoa and others. It can be inoculated in the eye postoperative following intraocular surgery, nonsurgical trauma or by hematogenous dissemination due to a systemic infection. The aim of this study was to report a case of bilateral bacterial endophthalmitis in a dog, with hypopyon, severe purulent secretion and melting ulcer. The microbiological diagnosis was made by culture and antibiogram after bilateral enucleation.

Endoftalmitis es un proceso inflamatorio grave que afecta el interior del globo ocular, lo que puede conducir a la ceguera y incluso la enucleación. Varios microorganismos están implicados en su patogénesis, tales como bacterias, virus, protozoos y similares. Estos pueden ser inoculados en el ojo después de la cirugía intraocular, del trauma quirúrgico o por vía hematógena debido a una infección sistémica. El objetivo de este trabajo es presentar un caso de endoftalmitis bacteriana bilateral en un perro, con hipopión severo, secreción purulenta y úlcera en melting. El diagnóstico microbiológico fue hecho por cultivo y antibiograma después de la enucleación bilateral.

Endoftalmite bacteriana severa bilateral em cão após facectomia intracapsular - relato de caso

A Endoftalmite é um processo inflamatório grave que acomete o interior do bulbo ocular, podendo levar à cegueira e até mesmo à enucleação. Vários micro-organismos estão envolvidos na sua etiopatogenia, tais como bactérias, vírus, protozoários e outros. Estes  podem ser inoculados no olho após cirurgias oftálmicas, traumas não cirúrgicos ou mesmo por via hematógena decorrente de uma infecção sistêmica. O objetivo deste trabalho foi relatar um caso de endoftalmite bacteriana bilateral em um cão, apresentando hipópio severo, secreção purulenta e úlcera em melting. O diagnóstico microbiológico foi realizado por meio da cultura e antibiograma após enucleação bilateral.