title: Effect of cryoprotectants on the porosity and stability of insulin-loaded PLGA nanoparticles after freeze-drying.
abstract: PLGA nanoparticles are useful to protect and deliver proteins in a localized or targeted manner, with a long-term systemic delivery pattern intended to last for a period of time, depending on polymer bioerosion and biodegradability. However, the principal concern regarding these carriers is the hydrolytic instability of polymer in aqueous suspension. Freeze-drying is a commonly used method to stabilize nanoparticles, and cryoprotectants may be also used, to even increase its physical stability. The aim of the present work was to analyze the influence of cryoprotectants on nanoparticle stability and porosity after freeze-drying, which may influence protein release and stability. It was verified that freeze-drying significantly increased the number of pores on PLGA-NP surface, being more evident when cryoprotectants are added. The presence of pores is important in a lyophilizate to facilitate its reconstitution in water, although this may have consequences to protein release and stability. The release profile of insulin encapsulated into PLGA-NP showed an initial burst in the first 2 h and a sustained release up to 48 h. After nanoparticles freeze-drying the insulin release increased about 18% in the first 2 h due to the formation of pores, maintaining a sustained release during time. After freeze-drying with cryoprotectants, the amount of insulin released was higher for trehalose and lower for sucrose, glucose, fructose and sorbitol comparatively to freeze-dried PLGA-NP with no cryoprotectant added. Besides the porosity, the ability of cryoprotectants to be adsorbed on the nanoparticles surface may also play an important role on insulin release and stability.
authors.affiliation: Centro de Investigação em Ciências da Saúde (CICS), Instituto Superior de Ciências da Saúde - Norte, CESPU, Gandra PRD, Portugal. pedrofonte86@gmail.com
authors.forename: Pedro
authors.initials: P
authors.lastname: Fonte
authors.forename: Sandra
authors.initials: S
authors.lastname: Soares
authors.forename: Ana
authors.initials: A
authors.lastname: Costa
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Andrade
authors.forename: Vítor
authors.initials: V
authors.lastname: Seabra
authors.forename: Salette
authors.initials: S
authors.lastname: Reis
authors.forename: Bruno
authors.initials: B
authors.lastname: Sarmento
mesh_terms: D003451:Cryoprotective Agents / Q000737:chemistry*; D016503:Drug Delivery Systems; D005612:Freeze Drying; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D011994:Recombinant Proteins / Q000008:administration & dosage; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry; D013997:Time Factors
chemical_list: D003451:Cryoprotective Agents; D007328:Insulin; D011994:Recombinant Proteins; D013501:Surface-Active Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: PLGA; cryoprotectants; freeze-drying; insulin; nanoparticles; porosity; release profile; surface