Screening of process parameters for the formulation of alginate microparticles with efficient encapsulation of fragile molecules using a Plackett-Burman design.

Synthia Mackin-Mohamour (1) , Thierry Bastogne (2, 3, 4) , Lucie Hassler (4) , Julia Budzinski (4) , Thierry Roques-Carmes (5) , Véronique Sadtler (5) , Maud Lebrun (5) , Philippe Marchal (5) , Anne Sapin-Minet (1) , Marianne Parent (1)

1 CITHEFOR - Cibles thérapeutiques, formulation et expertise pré-clinique du médicament
2 CRAN - Centre de Recherche en Automatique de Nancy
3 BIGS - Biology, genetics and statistics
4 CYBERnano [Villers-lès-Nancy]
5 LRGP - Laboratoire Réactions et Génie des Procédés

Peptide drugs efficacy and safety are often limited by instability, short half-life, immunogenicity and their hydrophilic nature which compromises their transport across biological membranes. These limitations could be addressed by polymeric formulations produced with processes adapted to these hydrophilic and labile drugs. For example, S-nitrosoglutathione (GSNO) is a tripeptide, highly hydrophilic, and physiological form of storage of nitric oxide (NO). NO is involved in several physiological processes, particularly in the cardiovascular system. It inhibits platelet aggregation, prevents endothelial dysfunction and promotes vasodilation but NO bioavailability is decreased both by ageing and various diseases. GSNO has been shown to be safe in clinical trials and effective in various preclinical models. However, GSNO needs to be presented in an adapted galenicform for using as a prodrug for oral administration. Consequently, we have developed several polymeric particles based on alginate obtained by emulsion/gelation process that target the following specifications: efficient encapsulation of hydrophilic molecules, with a particle size control, release control. An optimization of the formulation is currently proposed. A model compound (FCF sun yellow) with similar physicochemical properties to GSNO is used during particle development, to facilitate the analytical steps. A 4-factor Plackett-Burman experimental design was carried out to optimize the formulation process using the Quality by Design development paradigm, including one critical material attribute and three process parameters. The physico-chemical characterization of particles was performed to identify the optimized process and formulation parameters.

Domaines: Traitement du signal et de l'image [eess.SP]; Applications [stat.AP]; Cancer; Micro et nanotechnologies/Microélectronique

Synthia Mackin-Mohamour, Thierry Bastogne, Lucie Hassler, Julia Budzinski, Thierry Roques-Carmes, et al.. Screening of process parameters for the formulation of alginate microparticles with efficient encapsulation of fragile molecules using a Plackett-Burman design.. 20e édition des Journées de Formulation : Substitution et Reformulation, Nov 2021, Compiègne, France. ⟨hal-03548139⟩