Influence of lyophilization and cryoprotection on the stability and morphology of drug-loaded poly(ethylene glycol-b-ε-caprolactone) micelles

Simple item page
dc.contributor.authorHussain, MSen_AU
dc.contributor.authorFaisal, KSen_AU
dc.contributor.authorClulow, AJen_AU
dc.contributor.authorAlbrecht, Hen_AU
dc.contributor.authorKrasowska, Men_AU
dc.contributor.authorBlencowe, Aen_AU
dc.date.accessioned2023-06-30T01:34:27Zen_AU
dc.date.available2023-06-30T01:34:27Zen_AU
dc.date.issued2023-04-21en_AU
dc.date.statistics2023-05-16en_AU
dc.description.abstractPolymeric micelles are promising carriers for the delivery of poorly water-soluble drugs, providing enhanced drug solubility, blood circulation times, and bioavailability. Nevertheless, the storage and long-term stability of micelles in solution present challenges requiring the lyophilization and storage of formulations in the solid state, with reconstitution immediately prior to application. Therefore, it is important to understand the effects of lyophilization/reconstitution on micelles, particularly their drug-loaded counterparts. Herein, we investigated the use of β-cyclodextrin (β-CD) as a cryoprotectant for the lyophilization/reconstitution of a library of poly(ethylene glycol-b-ε-caprolactone) (PEG-b-PCL) copolymer micelles and their drug-loaded counterparts, as well as the effect of the physiochemical properties of different drugs (phloretin and gossypol). The critical aggregation concentration (CAC) of the copolymers decreased with increasing weight fraction of the PCL block (fPCL), plateauing at ~1 mg/L when the fPCL was >0.45. The blank (empty) and drug-loaded micelles were lyophilized/reconstituted in the absence and presence of β-CD (9% w/w) and analyzed via dynamic light scattering (DLS) and synchrotron small-angle X-ray scattering (SAXS) to assess for changes in aggregate size (hydrodynamic diameter, Dh) and morphology, respectively. Regardless of the PEG-b-PCL copolymer or the use of β-CD, the blank micelles displayed poor redispersibility (<10% relative to the initial concentration), while the fraction that redispersed displayed similar Dh to the as-prepared micelles, increasing in Dh as the fPCL of the PEG-b-PCL copolymer increased. While most blank micelles displayed discrete morphologies, the addition of β-CD or lyophilization/reconstitution generally resulted in the formation of poorly defined aggregates. Similar results were also obtained for drug-loaded micelles, with the exception of several that retained their primary morphology following lyophilization/reconstitution, although no obvious trends were noted between the microstructure of the copolymers or the physicochemical properties of the drugs and their successful redispersion. Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) licenceen_AU
dc.description.sponsorshipMSH thanks the University of South Australia for scholarship support. Part of this research was undertaken on the SAXS/WAXS beamline at the Australian Synchrotron, part of ANSTO. The authors thank the Australian Synchrotron for providing access to facilities and expertise. The authors also acknowledge the SasView application, originally developed under NSF Award DMR-0520547.en_AU
dc.identifier.articlenumber1974en_AU
dc.identifier.citationHussain, M. S., Faisal, K. S., Clulow, A. J., Albrecht, H., Krasowska, M., & Blencowe, A. (2023). Influence of lyophilization and cryoprotection on the stability and morphology of drug-loaded poly(ethylene glycol-b-&epsilon;-caprolactone) micelles. Polymers, 15(8), 1974. doi:10.3390/polym15081974en_AU
dc.identifier.issn2073-4360en_AU
dc.identifier.issue8en_AU
dc.identifier.journaltitlePolymersen_AU
dc.identifier.urihttps://doi.org/10.3390/polym15081974en_AU
dc.identifier.urihttps://apo.ansto.gov.au/handle/10238/15076en_AU
dc.identifier.volume15en_AU
dc.language.isoenen_AU
dc.publisherMDPIen_AU
dc.subjectDrugsen_AU
dc.subjectSolid state physicsen_AU
dc.subjectSmall angle scatteringen_AU
dc.subjectCopolymersen_AU
dc.subjectLyophilizationen_AU
dc.subjectSpectrophotometryen_AU
dc.subjectPolymersen_AU
dc.titleInfluence of lyophilization and cryoprotection on the stability and morphology of drug-loaded poly(ethylene glycol-b-ε-caprolactone) micellesen_AU
dc.typeJournal Articleen_AU
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
polymers-15-01974-v3.pdf
Size:
1.89 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.63 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Journal Articles