TY - JOUR
T1 - Evaluation of a combined drug-delivery system for proteins assembled with polymeric nanoparticles and porous microspheres; Characterization and protein integrity studies
AU - Alcalá-Alcalá, Sergio
AU - Benítez-Cardoza, Claudia G.
AU - Lima-Muñoz, Enrique J.
AU - Piñón-Segundo, Elizabeth
AU - Quintanar-Guerrero, David
N1 - Publisher Copyright:
© 2015 Elsevier B.V. All rights reserved.
PY - 2015/7/15
Y1 - 2015/7/15
N2 - This work presents an evaluation of the adsorption/infiltration process in relation to the loading of a model protein, α-amylase, into an assembled biodegradable polymeric system, free of organic solvents and made up of poly(d,l-lactide-co-glycolide) acid (PLGA). Systems were assembled in a friendly aqueous medium by adsorbing and infiltrating polymeric nanoparticles into porous microspheres. These assembled systems are able to load therapeutic amounts of the drug through adsorption of the protein onto the large surface area characteristic of polymeric nanoparticles. The subsequent infiltration of nanoparticles adsorbed with the protein into porous microspheres enabled the controlled release of the protein as a function of the amount of infiltrated nanoparticles, since the surface area available on the porous structure is saturated at different levels, thus modifying the protein release rate. Findings were confirmed by both the BET technique (N2 isotherms) and in vitro release studies. During the adsorption process, the pH of the medium plays an important role by creating an environment that favors adsorption between the surfaces of the micro- and nano-structures and the protein. Finally, assays of α-amylase activity using 2-chloro-4-nitrophenyl-α-d-maltotrioside (CNP-G3) as the substrate and the circular dichroism technique confirmed that when this new approach was used no conformational changes were observed in the protein after release.
AB - This work presents an evaluation of the adsorption/infiltration process in relation to the loading of a model protein, α-amylase, into an assembled biodegradable polymeric system, free of organic solvents and made up of poly(d,l-lactide-co-glycolide) acid (PLGA). Systems were assembled in a friendly aqueous medium by adsorbing and infiltrating polymeric nanoparticles into porous microspheres. These assembled systems are able to load therapeutic amounts of the drug through adsorption of the protein onto the large surface area characteristic of polymeric nanoparticles. The subsequent infiltration of nanoparticles adsorbed with the protein into porous microspheres enabled the controlled release of the protein as a function of the amount of infiltrated nanoparticles, since the surface area available on the porous structure is saturated at different levels, thus modifying the protein release rate. Findings were confirmed by both the BET technique (N2 isotherms) and in vitro release studies. During the adsorption process, the pH of the medium plays an important role by creating an environment that favors adsorption between the surfaces of the micro- and nano-structures and the protein. Finally, assays of α-amylase activity using 2-chloro-4-nitrophenyl-α-d-maltotrioside (CNP-G3) as the substrate and the circular dichroism technique confirmed that when this new approach was used no conformational changes were observed in the protein after release.
KW - Adsorption/infiltration
KW - Polymeric nanoparticles
KW - Porous microspheres
KW - Protein delivery
KW - Protein formulation
UR - http://www.scopus.com/inward/record.url?scp=84929993257&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2015.04.074
DO - 10.1016/j.ijpharm.2015.04.074
M3 - Artículo
C2 - 25936624
SN - 0378-5173
VL - 489
SP - 139
EP - 147
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -