Freeze Drying of Polymer Nanoparticles and Liposomes Exploiting Different Saccharide-Based Approaches

Abstract

Biodegradable nanocarriers represent promising tools for controlled drug delivery. However, one major drawback related to their use is the long-term stability, which is largely influenced by the presence of water in the formulations, so to solve this problem, freeze-drying with cryoprotectants has been proposed. In the present study, the influence of the freeze-drying procedure on the storage stability of poly(lactide-co-glycolide) (PLGA) nanoparticles and liposomes was evaluated. In particular, conventional cryoprotectants were added to PLGA nanoparticle and liposome formulations in various conditions. Additionally, hyaluronic acid (HA), known for its ability to target the CD44 receptor, was assessed as a cryoprotective excipient: it was added to the nanocarriers as either a free molecule or conjugated to a phospholipid to increase the interaction with the polymer or lipid matrix while exposing HA on the nanocarrier surface. The formulations were resuspended and characterized for size, polydispersity index, zeta potential and morphology. It was demonstrated that only the highest percentages of cryoprotectants allowed the resuspension of stable nanocarriers. Moreover, unlike free HA, HA-phospholipid conjugates were able to maintain the particle mean size after the reconstitution of lyophilized nanoparticles and liposomes. This study paves the way for the use of HA-phospholipids to achieve, at the same time, nanocarrier cryoprotection and active targeting.

Enhancing chemical and physical stability of pharmaceuticals using freeze-thaw method: challenges and opportunities for process optimization through quality by design approach

“…On the other hand, freeze-thaw cycles can also induce changes in the morphology and size distribution of nanoparticles, especially for some types of polymers and surfactants. For example, freeze-thawing can induce the formation of new crystalline structures or modify the morphology of nanoparticles, leading to changes in particle size [ 82 , 83 ].…”

Hyaluronic Acid Nanogels: A Promising Platform for Therapeutic and Theranostic Applications

“…The presence of HA enables lyophilization and reconstitution of nanogels without altering their physicochemical properties or potency of the payloads [ 98 ]. HA acts as a cryoprotectant, preserving the physical properties of polymeric nanoparticles [ 99 ] and liposomes [ 100 , 101 ] during freeze–thaw cycles and reconstitution. As a result, HA nanogels can be subjected to drying technologies, which improves their shelf life and facilitates product distribution.…”