Microencapsulation of microbial derived indoles by spray drying

The indoles produced by human flora show potential activity against resistant pathogens and modulate inflammation and immunity, thus acting on both the host and microbiome. Indole-3-aldehyde (3-IAld), produced by host’s Lactobacilli, has recently been shown to preserve immune physiology at mucosal surfaces while inducing antimicrobial resistance. (23973224). The potential therapeutic action of 3-IAld is ascribable to its main target: the aryl hydrocarbon receptors (AHR) mainly located in the small intestine region. For this reason, the aim of the present study is to develop an 3-IAld gastro-resistant formulation for small intestine (SI) regional drug delivery. In this regard, the purpose is to limit drug release in the stomach to avoid undesired effect and to ensure controlled release in the proximal small intestine. Therefore, microencapsulation methods will be employed (17207416). For this purpose, we encapsulated 3-IAld in methacrylate microparticles (MP) (Eudragit) prepared by spray-drying technique. The spray-drying method is a fast-way to produce dry particles, controlling particle size, morphology and allowing control of particle’s properties. (19862804). However, attention should be taken in the determination of working conditions and equipment setup to reduce the chance of producing porous and irregular MP that may not warrant the wanted SI localization. Moreover, 3-IAld shows tendency to diffuse either in aqueous or polar organic solvents during polymer layer formation, reducing entrapment efficiency with part of 3-IAld localized on the surface of the MP. Different Eudragit types were employed, among them, S100 and L100 show the most desirable attributes in terms of pH solubility (pH ≥ 6.0 and ≥ 7.0, respectively). (10789067). Eudragit L100-S100 in combination (1:1), (1:3), (1:4) were used to prepare the MP and different ethanol-water solutions. The MP were evaluated for particle size, shape, surface morphology and elemental analysis, yield, drug content (DC), and were tested in vitro for their pH-dependent release by using simulated gastric and intestinal fluids. Initial formulations at 1:1 L100-S100 ratio showed high gastric release exceeding 50-60% at 1.5 hours. The release burst was correlated to high porosity and irregular shape of the obtained MP. Average DC was between 5-10% w/w. At 1:3 L100-S100 ratio the release dropped to about 30% and DC was increased up to 20% w/w. Spray-drying conditions were then set in order to shift toward a non-buckling condition in which denser and less porous MP are formed. In such a way, 3-IAld release was further reduced to nearly 20% at 1.5 hours. The MP obtained seem to be promising to be employed to deliver 3-IAld to the SI. Ongoing studies are aimed at reducing further 3-IAld gastric release while increasing drug content.