Optimization of a Dexamethasone and Vitamin E PLGA Microparticle Formulation Intended for Posterior Segment of the Eye to Cope with Patients’ Anti-Inflammatory Needs

Background: Biodegradable microspheres (MSs) are good candidates for intravitreal administration in the posterior segment of the eye. MSs can be formulated as injectable preparations and administered using syringes with small-gauge needles. To allow proper injectability and avoid patients’ discomfort, the MS size should be as small as possible. However, the relationships between size, encapsulation efficiency, and drug-release behavior in these systems are widely recognized. Methods: In an attempt to optimize this requirement, we present here interesting dexamethasone (Dxm), vitamin E and human serum albumin (HSA) biodegradable MSs in the 2–20 µm range, elaborated by employing a version of the single-emulsion extraction–evaporation method. The method employed here renders MSs in the 2–40 µm range. The present work focuses on evaluating the smaller fraction, the 2–20 µm range, including physicochemical characterization, image analysis, dexamethasone release assays, cytotoxicity, and injectability evaluations. Results: The 2–20 µm fraction represents 25–30% of the entire population, has an average particle size of 18 µm, is spherical in shape, and has a Dxm loading between 38 and 50 µm per mg of MSs. In addition, a comparative evaluation between both fractions was carried out to assess whether relevant therapeutic differences can be expected. The in vitro release studies showed that MSs sized 2–20 µm, when vitamin E and HSA were included, have a low burst effect and, after that, a biphasic release profile during the first 4 weeks, with a long sustained Dxm release phase. This suggests that they might be better suited to maintain therapeutically anti-inflammatory concentrations of Dxm in the vitreous than the 20–40 µm MSs fraction, which also had a controlled Dxm release but in very reduced amounts after the first week. Conclusions: This 2–20 µm MS system might represent a success for its advantages over the existing alternatives in the marketplace, such as dexamethasone implants. Among others, due to the minimized risk associated with their administration that does not need ocular surgery, and consequently, the better the patient’s adherence is expected, there can be a medical preference for this system for its ease of use and possibility of personalizing the dose.