How Poloxamer Addition in Hyaluronic-Acid-Decorated Biodegradable Microparticles Affects Polymer Degradation and Protein Release Kinetics

Polymeric microparticles (MPs) designed for the intravitreal administration of therapeutic proteins result in a prolonged half-life in the vitreous and can delay or discourage the onset of adverse effects inevitably related to this route of administration. Hence, here we designed MPs composed of a polymeric blend based on poly(lactic-co-glycolic) acid and poloxamers, externally decorated with hyaluronic acid. The MPs are intended for intravitreal administration of bovine serum albumin. In detail, a systematic formulative study aiming to shed light on the complex relationship between protein release rate and MP degradation rate was carried out by means of calorimetric and gel permeation chromatography analyses. We found out that poloxamer addition caused a compact MP matrix, which led to a slight modification of the degradation kinetics and a reduction in the initial BSA initial release, which is of the utmost importance to ensure a relatively regular BSA release. It must also be underlined that for acid-labile molecules such as proteins, the poloxamer’s presence induced complex and hardly predictable effects on MP degradation/protein release, due to the dynamic balance between the time-evolving hydrophilicity of MPs and the influence of poloxamers themselves on the PLGA degradation rate.

Controlled electrospray generation of non-spherical alginate microparticles

Electrospraying is a technique used to generate microparticles in a high throughput manner. For biomedical applications, a biocompatible electrosprayed material is often desirable. Using polymers, such as alginate hydrogels, makes it possible to create biocompatible and biodegradable microparticles that can be used for cell encapsulation, to be employed as drug carriers, and for use in 3D cell culturing. Evidence in the literature suggests that the morphology of the biocompatible microparticles is relevant in controlling the dynamics of the microparticles in drug delivery and 3D cell culturing applications. Yet, most electrospray-based techniques only form spherical microparticles, and there is currently no widely adopted technique for producing non-spherical microparticles at a high throughput. Here, we demonstrate the generation of non-spherical biocompatible alginate microparticles by electrospraying, and control the shape of the microparticles by varying experimental parameters such as chemical concentration and the distance between the electrospray tip and the particle-solidification bath. Importantly, we show that these changes to the experimental setup enable the synthesis of different shaped particles, and the systematic change in parameters, such as chemical concentration, result in monotonic changes to the particle aspect ratio. We expect that these results will find utility in many biomedical applications that require biocompatible microparticles of specific shapes.