## 1 Introduction  
The bioavailability of drugs to the posterior segment of the eye is still a significant challenge. Indeed, the administration of active molecules by indirect routes, such as topical and systemic, is of very low effectiveness due to the presence of blood-ocular barriers. These cause poor drug penetration within the vitreous body and, therefore, a sub-therapeutic quantity of drug at the affected site [1]. For these reasons, intravitreal drug administration is still considered necessary for the successful treatment of posterior eye segment pathologies, as well as those related to neovascularization [2, 3, 4]. Indeed, the treatment of such disorders requires the administration of angiogenesis inhibitors, and only their intravitreal injection consistently enables the delivery of therapeutic agents in loco [5, 6, 7]. However, chronic intravitreal drug administration commonly elicits severe complications, such as retinal detachment, cataracts, hemorrhages and endophthalmitis,which are progressively more likely as the treatment progresses [8; 9; 10]. In this context, the reduction of the injection frequency allows us, in principle, to delay or discourage the onset of these adverse effects. Consequently, accomplishing a sustained drug administration strategy within the intravitreal space is more desirable than repeated injections [2]. From this standpoint, microparticles (MPs) designed for the intravitreal administration of therapeutic proteins lead to a prolonged half-life in the vitreous in a way that is not influenced by its clearance [11]. In two recent works, biodegradable MPs based on poly (lactic-co-glycolic) acid (PLGA), externally decorated with hyaluronic acid (HA), were produced [12; 13]. In detail, the MPs were fabricated by a modified version of the double-emulsion solvent evaporation technique using a PLGA/poloxamer (POLOX) polymeric blend in the organic phase of the emulsion. POLOX are amphiphilic block copolymers of ethylene oxide and propylene oxide monomers and were used to enhance the affinity between lipophilic PLGA and hydrophilic HA [12; 13; 14; 15]. HA was chosen because it is a major constituent of the vitreous body of the eye, and this allows a high affinity between the MPs and the vitreous body [16]. Indeed, the presence of HA on the surfaces of MPs has been shown to discourage their free diffusion in simulated vitreous body (SVB) [13], which promises to prevent microcarriers from interfering with patient _visus_. Moreover, the produced MPs could sustain the release of bovine serum albumin (BSA), used as a model protein. It is known that PLGA degradation, which occurs through random ester bond cleavage, is triggered by water intrusion and catalyzed by acids [16; 17]. PLGA-based MPs undergo bulk erosion since water can penetrate the MP inner regions and the trapped acidic oligomers prompt further autocatalytic degradation of the polymer [18]. Indeed, autocatalysis strongly depends on the formulation approach and significantly affects protein release [19]. Furthermore, bulk degradation probably results in low pH values within MPs, which in turn may be detrimental for the biological activity of acid-labile moieties, such as proteins [20]. In this panorama, amphiphilic POLOX are expected to modify bulk PLGA degradation through multiple mechanisms. For example, they may interfere with the local pH drop, change the MP morphology, and/or induce MP plasticization. Importantly, the additive presence in PLGA-based MPs is expected to change the release kinetics and/or burst of the loaded molecule(s). To the best of our knowledge, there is no systematic study that reports on the relationship between the release profiles of a protein from MPs and its polymeric composition, on which the degradation kinetics depend. Hence, we aim to shed light on the complex relationship between the protein release rate and MP degradation rate.