Etoposide-Loaded Poly(Lactic-co-Glycolic Acid) Intravitreal Implants: In Vitro and In Vivo Evaluation

Abstract

Etoposide-loaded poly(lactic-co-glycolic acid) implants were developed for intravitreal application. Implants were prepared by a solvent-casting method and characterized in terms of content uniformity, morphology, drug-polymer interaction, stability, and sterility. In vitro drug release was investigated and the implant degradation was monitored by the percent of mass loss. Implants were inserted into the vitreous cavity of rabbits' eye and the in vivo etoposide release profile was determined. Clinical examination and the Hen Egg Test-Chorioallantoic Membrane (HET-CAM) method were performed to evaluate the implant tolerance. The original chemical structure of the etoposide was preserved after incorporation in the polymeric matrix, which the drug was dispersed uniformly. In vitro, implants promoted sustained release of the drug and approximately 57% of the etoposide was released in 50 days. In vivo, devices released approximately 63% of the loaded drug in 42 days. Ophthalmic examination and HET-CAM assay revealed no evidence of toxic effects of implants. These results tend to show that etoposide-loaded implants could be potentially useful as an intraocular etoposide delivery system in the future.

In vitro and in vivo evaluation of etoposide - silk wafers for neuroblastoma treatment

“…Compared to delivering the same amount of chemotherapeutic drugs intravenously, implanting the drug-loaded silk sponges into the center of the tumor significantly decreased tumor growth, with higher intra-tumoral drug concentration and lower drug concentration in plasma. Poly(lactic-co-glycolic acid) has been used to prepare etoposide loaded intravitreal implants where drug loading was 33.3% and the implant system released 57% of the drug in 50 days in vitro [31]. Recently, poly (L-lactic acid) (PLLA)/polyethylene glycol 4000 (PEG4000) sustained release etoposide implants were developed by direct compression of 40% drug, 50% PLLA and 10% PEG4000.…”

Recent Advances of Ocular Drug Delivery Systems: Prominence of Ocular Implants for Chronic Eye Diseases

“…In an effort to improve the stability and therapeutic activity and prolong residency, this approach was used to formulate inserts or implants for several therapeutic medications that had received approval for ocular use. These drugs include dexamethasone [ 480 ], acetazolamide [ 234 ], bimatoprost [ 387 ], etoposide [ 481 ], and dorzolamide [ 482 ]. Table 3 displays a list of the FDA-approved polymers or copolymers used in ocular preparations.…”

Long‐Acting Ocular Injectables: Are We Looking In The Right Direction?

“…[109] Synthetic polymers, including PLGA, PLA, and PCL have been tested as LAIs for chronic ocular diseases for sustained release of small molecules, such as etoposide, lupeol, and timolol maleate. [110][111][112][113] The release from biodegradable polymeric implants typically spans from weeks to a few months and can shift as the polymer degrades. For example, Durysta is a long-acting PLGA-based intracameral implant for the sustained delivery of a prostaglandin analog, bimatoprost, and was the first-in-class, FDA-approved in 2020 for the treatment of chronic glaucoma.…”