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• W4311763535 abstract "Oral delivery of therapeutic peptides faces substantial barriers, as peptides can be susceptible to denaturation, aggregation or hydrolysis in the stomach. This study explored the possibility to target enteric release of five model peptides, semaglutide, liraglutide, GLP-1, gonadorelin acetate and oxytocin acetate, by encapsulation in a novel, industrially scalable complex coacervation by spray drying process (CoCo process). The potential of the complex coacervated (CoCo) matrix to prevent release of peptides in water, and simulated gastric fluid at pH 1.8 (SGF), while fully releasing in simulated intestinal fluid at pH 7.4 (SIF) was examined. The CoCo matrix consisting of gelatin, alginate and succinic acid was marginally effective at preventing peptide release in SGF; however, incorporating latex with the CoCo formulation substantially limited release of semaglutide, liraglutide and GLP-1. From CoCo powders formulated with 0.25:1 ethylcellulose:alginates + gelatin, 12.3 ± 0.7% of semaglutide, 24.0 ± 0.5% of liraglutide, and 41.2 ± 0.7% of GLP-1 released in SGF after 2h incubation, reductions of 201–311% over CoCo powders without ethylcellulose. Alternate latexes including methacrylic acid copolymer and polyvinyl acetate phthalate, similarly decreased peptide release in the SGF. Notably, while successful control of semaglutide, liraglutide and GLP-1 release was achieved, encapsulation in CoCo powders with or without latex failed to limit the release of gonadorelin acetate or oxytocin acetate in SGF. The physicochemical properties of the peptides including size, net charge and hydrophobicity likely play a role in the extent to which peptides remain within the microcapsules in the aqueous suspensions. All peptides fully released in SIF as the complex coacervated matrix dissolves at the higher pH. Latex in the CoCo formulation had negligible impact on peptide release in the SIF. This study demonstrates the potential for formulation strategies to target enteric release of therapeutic peptides from complex coacervated powders formed by spray drying." @default.
• W4311763535 created "2022-12-28" @default.
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• W4311763535 date "2023-01-01" @default.
• W4311763535 modified "2023-09-25" @default.
• W4311763535 title "Targeting enteric release of therapeutic peptides by encapsulation in complex coacervated matrix microparticles by spray drying" @default.
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• W4311763535 doi "https://doi.org/10.1016/j.jddst.2022.104063" @default.
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