Stability Study Perspective of the Effect of Freeze-Drying Using Cryoprotectants on the Structure of Insulin Loaded into PLGA Nanoparticles

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Pedro Fonte (Author) Other; Sandra Soares (Author) Other; Flavia Sousa (Author) Other; Ana Costa (Author) Other; Vitor Seabra (Author) Other; Salette Reis (Author) FFUP; Bruno Sarmento (Author) Other

Journal

Title: Biomacromolecules

Vol. 15

Pages: 3753-3765

ISSN: 1525-7797

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 45 Citations

Scopus - 62 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-009-WGQ

DOI: 10.1021/bm5010383

Abstract (EN): This work aimed to evaluate the influence of a freeze-drying process using different cryoprotectants on the structure of insulin loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles and to assess the stability of these nanoparticles upon 6 months of storage following ICH guidelines. Insulin-loaded PLGA nanoparticles with a size around 450 nm were dehydrated using a standard freeze-drying cycle, using trehalose, glucose, sucrose, fructose, and sorbitol at 10% (w/v) as cryoprotectants. All formulations, except those nonadded of cryoprotectant and added with trehalose, collapsed after freeze-drying. The addition of cryoprotectants increased the nanoparticles stability upon storage. FTIR results showed that insulin maintained its structure after encapsulation in about 88%, decreasing to 71% after freeze-drying. The addition of cryoprotectants prior to freeze-drying increased insulin structural stability an average of up to 79%. Formulations collapsed after freeze-drying showed better protein stabilization upon storage, in special sorbitol added formulation, preserving 76, 80, and 78% of insulin structure at 4 degrees C, 25 degrees C/60% RH, and 40 degrees C/75% RH, respectively. Principal component analysis also showed that the sorbitol-added formulation showed the most similar insulin structural modifications among the tested storage conditions. These findings suggested that regarding nanoparticles stability, cryoprotectants are versatile to be used in a standard freeze-drying, however they present different performances on the stabilization of the loaded protein. Thus, on the freeze-drying of the nanoparticles field, this work gives rise to the importance of the process of optimization, searching for a balance between a good obtainable cake with an optimal structural stabilization of the loaded protein.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13