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. 2023 Jan 31;16(3):1212.
doi: 10.3390/ma16031212.

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

Ilaria Andreana  1 , Valeria Bincoletto  1 , Maela Manzoli  1 , Francesca Rodà  1 , Vita Giarraputo  1 , Paola Milla  1 , Silvia Arpicco  1 , Barbara Stella  1
Affiliations

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

Ilaria Andreana et al. Materials (Basel). .

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.

Keywords: cryoprotectants; freeze drying; hyaluronic acid; liposomes; nanoparticles.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the freeze-drying process for PLGA nanoparticles and liposomes formulated with different cryoprotectants (created with BioRender.com).
Figure 2
Figure 2
Chemical structures of the excipients used in this study.
Figure 3
Figure 3
PLGA 75:25 nanoparticle mean hydrodynamic diameter as a function of the percentage of the different cryoprotectants when added before pouring the acetone solution into the aqueous phase (n = 3, S.D. < 10% for all samples).
Figure 4
Figure 4
Schematic representation of the association of HA and HA-DPPE conjugates to polymer and lipid nanocarriers (created with BioRender.com).
Figure 5
Figure 5
Particle hydrodynamic diameter and PDI of liposomes before and after freeze-drying in the presence of free HA (n = 3).
Figure 6
Figure 6
Mean particle hydrodynamic diameter and PDI of rehydrated freeze-dried PLGA nanoparticles and liposomes with HA-DPPE conjugates (n = 3).
Figure 7
Figure 7
FESEM representative images of HA4.8-DPPE/PLGA 75:25 nanoparticles (a–c) and HA4.8-DPPE-liposomes (d–f) in their as prepared form (a,d), after freeze drying (b,e) and after resuspension (c,f). Images collected at 10 kV with the In-Beam SE detector. Instrumental magnification: 200,000× (a), 270,000× (d), 300,000× (b,f), 350,000× (c), and 550,000× (e), respectively.
See this image and copyright information in PMC

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