An Investigation into the Mechanism of Nanoparticle Aggregation Reduction of Polymeric Cryoprotectants

Abstract

In this study, polymeric protectants are examined in addition to traditional sugar-based protectants. The polymeric protectants include PEG 2000, PEG 3400, PEG 4600, PEG 20000, Pluronic F68, Pluronic F127, and Pluronic 104. The sugar-based protectants being studied are trehalose and mannitol. Using both DLS and HPLC techniques to record measurements, differences between the results for the freeze-thawing and freeze-drying processes demonstrate that the majority of aggregation of the nanoparticles occurs during the drying step. Of the non-sugar protectants, PEG 4600, PEG 20000, and Pluronic F68 performed the best for the freeze-drying and freeze-thawing processes. In addition, these three protectants showed no significant change when the freezing rate or freezing method was altered. This result could provide economic benefits when these nanoparticles are being used for pharmaceutical purposes. Since the method of freezing does not affect the particle size or the recovery of the active, the most inexpensive method of freezing can be selected for use. This work provides a fundamental analysis on the mechanism of nanoparticle aggregation reduction by polymeric protectants and how polymeric protectants are a viable alternative to sugar protectants.