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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.

SUBMITTER: Dutta D

PROVIDER: S-EPMC5482417 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Tunable delayed controlled release profile from layered polymeric microparticles.

Dutta D D Fauer C C Hickey K K Salifu M M Stabenfeldt S E SE

Journal of materials chemistry. B 20170313 23

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- ...[more]

PMID: 28652916

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Project description:Polymeric microparticles of polyethyleneglycol-polylactic acid-co-glycolic acid (PEG-PLGA) are widely used as drug carriers for a variety of applications due to their unique characteristics. Although existing techniques for producing polymeric drug carriers offer the possibility of achieving greater production yield across a wide range of sizes, these methods are improbable to precisely tune particle size while upholding uniformity of particle size and morphology, ensuring consistent production yield, maintaining batch-to-batch reproducibility, and improving drug loading capacity. Herein, we developed a novel scalable method for the synthesis of tunable-sized microparticles with improved monodispersity and batch-to-batch reproducibility via the coaxial flow-phase separation technique. The study evaluated the effect of various process parameters on microparticle size and polydispersity, including polymer concentration, stirring rate, surfactant concentration, and the organic/aqueous phase flow rate and volume ratio. The results demonstrated that stirring rate and polymer concentration had the most significant impact on the mean particle size and distribution, whereas surfactant concentration had the most substantial impact on the morphology of particles. In addition to synthesizing microparticles of spherical morphology yielding particle sizes in the range of 5-50 µm across different formulations, we were able to also synthesize several microparticles exhibiting different morphologies and particle concentrations as a demonstration of the tunability and scalability of this method. Notably, by adjusting key determining process parameters, it was possible to achieve microparticle sizes in a comparable range (5-7 µm) for different formulations despite varying the concentration of polymer and volume of polymer solution in the organic phase by an order of magnitude. Finally, by the incorporation of fluorescent dyes as model hydrophilic and hydrophobic drugs, we further demonstrated how polymer amount influences drug loading capacity, encapsulation efficiency, and release kinetics of these microparticles of comparable sizes. Our study provides a framework for fabricating both hydrophobic and hydrophilic drug-loaded microparticles and elucidates the interplay between fabrication parameters and the physicochemical properties of microparticles, thereby offering an itinerary for expanding the applicability of this method for producing polymeric microparticles with desirable characteristics for specific drug delivery applications.

Dataset Information

Tunable delayed controlled release profile from layered polymeric microparticles.

Publications

Tunable delayed controlled release profile from layered polymeric microparticles.

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