Continuous supercritical emulsion extraction for the co-encapsulation of butyrate and propionate nanoparticles in PLGA microparticles for colonic release

Abstract

Postbiotics are substances released or produced by the metabolic activity of microorganisms that have a beneficial effect on the host. Among the postbiotics, butyrate and propionate stand out for their excellent anti-inflammatory and immunomodulatory properties in the fight against intestinal diseases. However, these substances have some limitations as they are low molecular weight compounds that have limited clinical use due to unfavorable pharmacokinetics, non-selective pharmacological action, poor palatability and unpleasant odor.

Encapsulation in microparticles, designed for specific delivery to the colon, is a relevant strategy to prevent premature degradation or release of nanoparticles during their passage through the upper gastrointestinal tract, allowing for the targeted drug delivery to the colon by oral administration. In this study, we developed an oral multifunctional system based on nano-in-microparticles, processed by supercritical emulsion extraction to achieve targeted colonic release of butyrate and propionate. The nano-in-microparticles exhibited a diameter of about 1340 nm, an encapsulation efficiency of approximately 39 % for propionate and 36 % for butyrate.

They proved to be efficient when compared to the ones obtained by solvent evaporation. In vitro release studies showed that the encapsulation of the nanoparticles in PLGA microparticles promoted a larger control of the release rate of postbiotics, with a significant reduction in acidic media when compared to nanoparticles that were completely released before reaching the colonic pH. This work represents an innovative approach, since there are few reports in the literature on the encapsulation of postbiotics and, to date, no study has described the development of nano-in-microparticle systems aimed specifically at the colonic release of post-biotics such as butyrate and propionate.

Materials

Poly-lactic-co-glycolic-acid (RESOMER 504 H; ratio 50:50; Mw 38,000–54,000) was acquired from Evonik Industries (Denmark). Butyrate (catalogue code: B5887), propionate (catalogue code: P1880), phosphoric acid (PhA), and Tween® 80 were purchased from Sigma-Aldrich (USA). Ethanol, acetonitrile (ACN), ethyl acetate (EA), and potassium chloride were supplied from Carlo Erba Reagents (Italy). Hyaluronic acid was purchased from Vitafarma (Brazil).

Suzana Gonçalves Carvalho, Ernesto Reverchon, Mariarosa Scognamiglio, Lucia Baldino, Marlus Chorilli, Continuous supercritical emulsion extraction for the co-encapsulation of butyrate and propionate nanoparticles in PLGA microparticles for colonic release, Colloids and Surfaces A: Physicochemical and Engineering Aspects, Volume 725, Part 2, 2025, 137606, ISSN 0927-7757, https://doi.org/10.1016/j.colsurfa.2025.137606.