title: Critical attributes of formulation and of elaboration process of PLGA-protein microparticles.
abstract: Low drug loading, burst effect during release and drug inactivation account for the main drawbacks of protein microencapsulation in poly(d,l-lactic-co-glycolic) acid (PLGA) matrix by the water-in oil-in water (W/O/W) solvent evaporation method. Thus, the current study was set to invest the critical attributes of formulation and of elaboration process which determine protein loading into microparticles as well as its further release, using albumin as protein model. NaCl concentration in the external aqueous phase, poly(vinyl alcohol) (PVA) concentration and mostly viscosity of both the internal aqueous phase and the organic phase were critical attributes for improving drug loading, with polymer molecular weight and hydrophobicity likewise directly related to albumin loading. In such a way, when using 0.5% PVA as internal aqueous phase the highest albumin loading was achieved. Optimized microparticles exhibited a sustained in vitro release of albumin over 130 days. The influence of the microencapsulation process on albumin stability and biological activity was evaluated by carrying out cell proliferation assays on PC12 cells with albumin released from microparticles. Such assay demonstrated that the microencapsulation procedure optimized in this study did not affect the biological stability of the microencapsulated protein.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Martín-Sabroso
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Spain.
authors.forename: A I
authors.initials: AI
authors.lastname: Fraguas-Sánchez
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Aparicio-Blanco
authors.affiliation: Clinical Pharmacology, Health Research Institute, La Princesa University Hospital, Madrid, Spain; Teófilo Hernando Institute, Madrid, Spain; Department of Pharmacology and Therapeutics, Faculty of Medicine, Autonomous University of Madrid, Spain.
authors.forename: M F
authors.initials: MF
authors.lastname: Cano-Abad
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Spain; Institute of Industrial Pharmacy, Complutense University of Madrid, Spain. Electronic address: galaaaa@ucm.es.
authors.forename: A I
authors.initials: AI
authors.lastname: Torres-Suárez
mesh_terms: D000418:Albumins / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations; D065546:Drug Liberation; D057927:Hydrophobic and Hydrophilic Interactions; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D008970:Molecular Weight; D016716:PC12 Cells; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D012965:Sodium Chloride / Q000737:chemistry; D012997:Solvents / Q000737:chemistry
chemical_list: D000418:Albumins; D003692:Delayed-Action Preparations; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D012965:Sodium Chloride
keywords: Albumin; Critical attributes; Microparticles; Poly(lactic-co-glycolic) acid; Protein microencapsulation; Quality by design