<p>Efficacy of Sub-Tenon Micro-Perfusion of Cyclophosphamide in Rabbits with Severe Ocular Inflammation</p>

Abstract

Purpose To explore the feasibility of cyclophosphamide (CP) via a sub-Tenon micro-perfusion system (SMS) in rabbits, and assess its therapeutic efficacy in severe ocular inflammation. Materials and Methods Distribution and pharmacokinetics of CP were evaluated in vivo, and the concentrations of CP in plasma, vitreous humor, and retina/choroid were quantitated by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) at different time points. After induction of severe experimental uveitis, rabbits were divided into three groups (n=8 in each): the SMS group, subconjunctival injection (SI) group, and control group. Clinical inflammatory score was assessed in rabbits. Electroretinography and histopathology were performed on post-treatment day 8. Statistical analyses were performed using Mann–Whitney and Kruskal–Wallis tests. P -value less than 0.05 was considered significant. Results The concentrations of CP in vitreous humor and retina/choroid in the SMS group were significantly higher than that of the SI group at 3, 6, 10, and 24 hours ( P <0.01), while plasmatic CP concentrations were comparable at all time points in the SMS group and SI group ( P >0.05). The SMS group showed significantly less inflammation compared to the control group and SI group. Furthermore, the restoration of retinal structure and function were more obvious in the SMS group compared with conventional SI application. Conclusion Sub-Tenon micro-perfusion of CP exhibited satisfied therapeutic efficacy in rabbits with severe ocular inflammation and may provide a promising alternative for controlling ocular inflammatory disease and immune-mediated ocular diseases.

A Review of Ocular Drug Delivery Platforms and Drugs for Infectious and Noninfectious Uveitis: The Past, Present, and Future

“…In rabbits with severe uveitis following injection of Mycobacterium tuberculosis antigen, a prolonged infusion (1 h or more) of sub-Tenon’s cyclophosphamide resulted in high concentrations of the drug within the vitreous and retina and a significant improvement in inflammation compared to controls [ 40 ]. There was minimal systemic absorption found [ 40 ].…”

“…In rabbits with severe uveitis following injection of Mycobacterium tuberculosis antigen, a prolonged infusion (1 h or more) of sub-Tenon’s cyclophosphamide resulted in high concentrations of the drug within the vitreous and retina and a significant improvement in inflammation compared to controls [ 40 ]. There was minimal systemic absorption found [ 40 ]. While this proof-of-concept study was interesting, these results seem impractical to replicate clinically currently due to the need of an extended sub-Tenon’s infusion through a catheter unless another, more rapid delivery platform can be developed.…”

Resultado da ação da ciclofosfamida x mitomicina c em coelhos submetidos à trabeculectomia

“…A ciclofosfamida (CF) é um agente antineoplásico, alquilante, já utilizado para tratamento de várias doenças sistêmicas, inclusive com ação inibitória para a proliferação de fibroblastos, e agindo também na diminuição da produção de colágeno, como, por exemplo, na esclerose múltipla (17). Em Oftalmologia, ela foi descrita pela primeira vez em 1952 para o tratamento de uveítes de formas desconhecidas (18). É um potente imunossupressor prescrito para controle de doenças inflamatórias graves e atua como um agente alquilante através de ligações cruzadas do DNA.…”