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.

Preparation and in vivo evaluation of insulin-loaded biodegradable nanoparticles prepared from diblock copolymers of PLGA and PEG

“…Alternatively, the use of sonication as the source of agitation to form the two emulsion types preserves the physical and chemical stability of insulin during NP fabrication (Fonte et al, 2012;Sarmento et al, 2007;Sheshala et al, 2009). However, low encapsulation efficiency (Sarmento et al, 2007;Sheshala et al, 2009) and high initial burst effect (Fonte et al, 2012;Ibrahim et al, 2005) are observed.…”

The influence of freeze drying and ϒ-irradiation in pre-clinical studies of flurbiprofen polymeric nanoparticles for ocular delivery using D-(+)-trehalose and polyethylene glycol

“…Approximately 92%-94% of FB amount was released in the first 10 hours from FD-NPsTRE and IR-NPsTRE, respectively, as shown in Figure 1C and D. TRE was reported as a protectant agent that induces or increases the porosity of NPs. 39 It may open a pathway for a faster FB release from NPs and for its possible degradation by external factors. Two mechanisms of pore formation have been postulated, and it is probable that both contribute to the higher FB release rate.…”

Functionalizing PLGA and PLGA Derivatives for Drug Delivery and Tissue Regeneration Applications

“…[103] Thus, Fonte et al suggested the lyophilization of PLGA nanoparticles to improve the long-term stability, reducing the instability of protein-loaded PLGA nanoparticles formulations. [104] However, to reduce the aggregation of PLGA nanoparticles and physical stress caused by ice crystals, lyoprotectants should be added to PLGA nanoparticles formulations. Fonte et al studied the influence of 5 different lyoprotectants in insulin-loaded PLGA nanoparticles stability after lyophilization.…”