Development of the Latanoprost Solid Delivery System Based on Poly(l-lactide-co-glycolide-co-trimethylene carbonate) with Shape Memory for Glaucoma Treatment

Abstract

Latanoprost (LTP) is a prostaglandin F2α analog used to lower intraocular pressure in glaucoma treatment administered daily as eye drops. In this study, a universal model based on poly(l-lactide-co-glycolide-co-trimethylene carbonate) with shape memory was proposed for the development of a solid biodegradable formulation with prolonged release administered intraconjunctivally, intravitreally, subconjunctivally, and subcutaneously. Solution casting and electron beam (EB) irradiation were applied to the matrix formulation. The properties of the native matrix and matrices degraded in a PBS buffer (pH 7.4) were monitored by NMR, DSC, GPC, and SEM. Water uptake (WU) and weight loss (WL) were also analyzed. LTP was released over 113 days in a tri-phasic and sigmoidal pattern without a burst effect and with a relatively long second release phase, in which changes were observed in the glass transition temperature, molecular weight (Mn), WU, and WL. EB irradiation decreased the initial Mn, increased WU, and accelerated LTP release with a shortened lag phase. This provides the opportunity to partially eliminate the use of drops at the start of treatment. SEM observations indicated that surface erosion is the prevalent degradation mechanism. The proposed model is an interesting solution during a preliminary study to develop final medicinal products that provide high adherence.