PLA-PEG Implant as a Drug Delivery System in Glaucoma Surgery: Experimental Study

Abstract

Excessive postoperative scarring halts the effectiveness of glaucoma surgery and still remains a challenging problem. The purpose of this study was to develop a PLA-PEG-based drug delivery system with cyclosporine A or everolimus for wound healing modulation. Methods: PLA-PEG implants saturation with cyclosporine A or everolimus as well as their further in vitro release were analyzed. Anti-proliferative activity and cytotoxicity of the immunosuppressants were studied in vitro using human Tenon’s fibroblasts. Thirty-six rabbits underwent glaucoma filtration surgery with the application of sham implants or samples saturated with cyclosporine A or everolimus. The follow-up period was six months. A morphological study of the surgery area was also performed at seven days, one, and six months post-op. Results: PLA-PEG implants revealed a satisfactory ability to cumulate either cyclosporine A or everolimus. The most continuous period of cyclosporine A and everolimus desorption was 7 and 13 days, respectively. Immunosuppressants demonstrated marked anti-proliferative effect regarding human Tenon’s fibroblasts without signs of cytotoxicity at concentrations provided by the implants. Application of PLA-PEG implants saturated with immunosuppressants improved in vivo glaucoma surgery outcomes. Conclusions: Prolonged delivery of either cyclosporine A or everolimus by means of PLA-PEG implants represents a promising strategy of wound healing modulation in glaucoma filtration surgery.

Nanofiber‐based glaucoma drainage implant improves surgical outcomes by modulating fibroblast behavior

“…Fourteen and 28 days after implantation, bleb morphology was graded by examining sedated animals using the Indiana Bleb Appearance Grading Scale (IBAGS) to assign numerical scores for height, extent, and vascularity based on standardized photos. This method has previously been used in rabbit models of glaucoma surgery to evaluate bleb morphology in response to small molecule therapies and device‐specific modifications in preventing scar formation 68–71 . Implant migration was assessed by measuring the distance between the distal end of the GDI within the anterior chamber to the corneal limbus at baseline immediately after implantation, and then at 14 and 28 days post implantation.…”

“…This method has previously been used in rabbit models of glaucoma surgery to evaluate bleb morphology in response to small molecule therapies and device‐specific modifications in preventing scar formation. 68 , 69 , 70 , 71 Implant migration was assessed by measuring the distance between the distal end of the GDI within the anterior chamber to the corneal limbus at baseline immediately after implantation, and then at 14 and 28 days post implantation. For assessing GDI patency, rabbits were sedated and proparacaine hydrochloride drops were administered topically.…”

Material and Design Toolkit for Drug Delivery: State of the Art, Trends, and Challenges

“…In vitro release, antiproliferative activity, and cytotoxicity studies were analyzed using human Tenon’s fibroblasts. They could reach up to 7 days of continuous delivery of cyclosporine A. , …”

Pharmacological modulation of wound healing in glaucoma surgery

“…Системное применение ЦсА показано при увеитах, ассоциированных с ювенильным ревматоидным артритом. Экспериментальное исследование на кроликах, изучающее эффективность конъюнктивальных инстилляций 2% раствора ЦсА в послеоперационном периоде, продемонстрировало улучшение результатов гипотензивных вмешательств при сроке наблюдения 2 месяца [26]. Изучение влияния эпибульбарного применения 0,05% эмульсии ЦсА у пациентов после гипотензивной хирургии выявило положительное воздействие на гипотензивный эффект проведенных операций в одних исследованиях [27] и незначительное влияние на уровень ВГД в других [28].…”

“…Изучение влияния эпибульбарного применения 0,05% эмульсии ЦсА у пациентов после гипотензивной хирургии выявило положительное воздействие на гипотензивный эффект проведенных операций в одних исследованиях [27] и незначительное влияние на уровень ВГД в других [28]. Проведенные исследования по изучению токсичности ЦсА в отношении тканей и клеток глаза показали безопасность препарата для эндотелия роговицы, конъюнктивы и пигментного эпителия сетчатки [26].…”