Tunable delayed controlled release profile from layered polymeric microparticles

Abstract

Composite microparticles (MPs) with layered architecture, engineered from poly(L-lactic acid) (PLLA) and poly(D,L-lactic-co-glycolic acid) (PLGA), are promising devices for achieving the delayed release of proteins. Here, we build on a water-in-oil-in-oil-in-water emulsion method of fabricating layered MPs with an emphasis on modulating the delay period of the protein release profile. Particle hardening parameters (i.e. polymer precipitation rate and total hardening time) following water-in-oil-in-oil-in-water emulsions are known to affect MP structure such as the core/shell material and cargo localization. We demonstrate that layered MPs fabricated with two different solvent evaporation parameters not only alter polymer and protein distribution within the hardened MPs, but also affect their protein release profiles. Secondly, we hypothesize that ethanol (EtOH), a semi-polar solvent miscible in both the solvent (dichloromethane; DCM) and non-solvent aqueous phases, likely alters DCM and water flux from the dispersed oil phase. The results reveal that EtOH affects protein distribution within MPs, and may also influence MP structural properties such as porosity and polymer distribution. To our knowledge, we are the first to demonstrate EtOH as a means for modulating critical release parameters from protein-loaded, layered PLGA/PLLA MPs. Throughout all the groups in the study, we achieved differential delay periods (between 0 – 30 days after an initial burst release) and total protein release periods (~30 – >58 days) as a function of solvent evaporation parameters and EtOH content. The layered MPs proposed in the study potentially have wide-reaching applications in tissue engineering for delayed and sequential protein release.

An ultraviolet‐curable, core–shell vaccine formed via phase separation

“…Emulsion‐based techniques, which are commonly used for fabricating micro‐ and nanoparticle, expose cargo to both organic and aqueous solvents (Berkland, Pollauf, Pack, & Kim, ; Bilati, Allemann, & Doelker, ). In the case of amino acid‐based cargo, solvent exposure can lead to protein aggregation and denaturation, resulting in reduced therapeutic efficacy (Dutta, Fauer, Hickey, Salifu, & Stabenfeldt, ; Souery et al, ). To address the need for reduced solvent exposure, alternative fabrication methods, such as the StampEd Assembly of polymer Layers (SEAL) technique, have been developed (Soliz et al, ).…”

Biodegradable Microparticles for Regenerative Medicine: A State of the Art and Trends to Clinical Application

“…Porous silica materials are known to have a high drug-loading potential, and its encapsulation in biodegradable polymer PLGA via double emulsification method may help control and extend drug release where both components contribute to it [ 60 , 61 ]. Further, layered polymer-based microparticles engineered from PLGA with PLLA or PCL, respectively, via double emulsification may provide delayed predictable protein release, which is a promising feature in drug delivery [ 62 ]. This technique also allows step-by-step incorporation of functional additives, e.g., hydroxyapatite and silver nanoparticles, for introducing both cytocompatibility and antibacterial activity [ 63 ].…”

Core -Shell Particles: from Fabrication Methods to Diverse Manipulation Techniques

“…[63] Polymers such as PLGA, Glu-PLGA, PDLLA, chitosan, and alginate are employed. [64,64,65] This widely used process is simple to setup and offers a wide range of material choices. However, the low monodispersity and difficulty in scaling up remain the limitations of this process.…”