Development study of pectin/Surelease® solid microparticles for the delivery of L-alanyl-L-glutamine dipeptide
2019
Nova, Mônica Villa | Nothnagel, Lisa | Thurn, Manuela | Travassos, Patrícia B. | Herculano, Leandro S. | Bittencourt, Paulo R.S. | Novello, Cláudio R. | Bazotte, Roberto B. | Wacker, Matthias G. | Bruschi, Marcos Luciano
In this study, microparticles comprising L-alanyl-L-glutamine (AGP) were developed. A combination of pectin and Surelease® (ethylcellulose aqueous dispersion) was responsible for sustained AGP release properties in the gastrointestinal tract. A multiparameter optimization was conducted using a 23 factorial design. A broad array of formulation attributes were investigated (morphology, size, polydispersity, and entrapment efficiency) to identify suitable formulation candidates. Afterwards, two preparations (f7 and f8) varying in their pectin:Surelease® ratio were selected for further characterization (TG/DSC, XRD, FTIR, in vitro release and in vivo study). The factorial design revealed a strong influence of drying temperature on particle size and AGP entrapment efficiency. Thermal and spectroscopic analyses confirmed stability of the formulations at up to 200 °C as well as an effective encapsulation of the dipeptide. A small but not significant difference in the in vitro release profiles was found. However, in the in vivo test, formulation f8 presented a quicker effect of AGP in comparison to f7 in an animal model of insulin-induced hypoglycemia, suggesting that the higher concentration of the hydrophilic polymer pectin in f8 contributes to a faster release and bioavailability. Therefore, this study showed the possibility of encapsulating AGP using pectin and Surelease® with preserved activity of the dipeptide, and depending on the intended time and duration for action, other polymer ratios can be tested.
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