# The effect of cryoprotectant and storage conditions on the aggregation of poly(ethylene glycol)-poly(α-benzyl carboxylate-ε-caprolactone) nanoparticles

## TL;DR

This study finds the best way to store specific nanoparticles to prevent them from clumping together during storage.

## Contribution

The study identifies optimal cryoprotectants and storage methods to minimize nanoparticle aggregation in PEG-PBCL NPs.

## Key findings

- PEG3350 and methoxy-PEG 5000 at a 4:1 ratio minimized size growth during freeze-drying.
- Freeze-thawing with sucrose or PEGs prevented significant nanoparticle aggregation.
- Freeze-thawing was found to be better than freeze-drying for storing PEG-PBCL NPs.

## Abstract

The preparation of nanoparticles (NPs) in aqueous media leads to thermodynamic instability and aggregation during storage. The objective of this study was to identify an optimum condition for the storage of poly(ethylene glycol)-poly(α-benzyl carboxylate-ε-caprolactone) (PEG-PBCL) NPs with minimum to no NP aggregation.

Nanoparticles were prepared from PEG-PBCL of varied PBCL degrees of polymerization. Prepared NPs were either subjected to freeze-thaw or lyophilization with the addition of sugars or polyethylene glycols (PEGs) of varying molecular weight. The average diameter and polydispersity of NPs before and after freeze-thaw or lyophilization/reconstitution in water was assessed by dynamic light scattering and transmission electron microscopy (TEM). Differential Scanning Calorimetry (DSC) was used to compare the thermal behaviour of NPs before and after selected storage conditions.

Irrespective of the DP of PBCL, minimum size growth in the freeze-drying method was achieved when PEG3350 and methoxy-PEG 5000 were used as cryoprotectant at a w/w ratio of 4:1 to PEG-PBCL. Under this condition, NP size increased about 2-fold after reconstitution. In the freeze-thaw method, both sucrose and PEGs of different molecular weights, protected the PEG-PBCL NPs of different PBCL length from significant size growth where average particle size growth was not more than 1.20 folds.

Our findings suggest that freeze-thawing of PEG-PBCL NP using sucrose or PEG can prevent the NP aggregation and is the best method for PEG-PBCL NP storage.