Impact of small molecule and reverse poloxamer addition on the micellization and gelation mechanisms of poloxamer hydrogels

Michelle A Calabrese, Joanna M White

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Poloxamer 407 (P407) is widely used for targeted drug-delivery because it exhibits thermoresponsive gelation behavior near body temperature, stemming from a disorder-to-order transition. Hydrophobic small molecules can be encapsulated within P407; however, these additives often negatively impact the rheological properties and lower the gelation temperatures of the hydrogels, limiting their clinical utility. Here we investigate the impact of adding two BAB reverse poloxamers (RPs), 25R4 and 31R1, on the thermal transitions, rheological properties, and assembled structures of P407 both with and without incorporated small molecules. By employing a combination of differential scanning calorimetry (DSC), rheology, and small-angle x-ray scattering (SAXS), we determine distinct mechanisms for RP incorporation. While 25R4 addition promotes inter-micelle bridge formation, the highly hydrophobic 31R1 co-micellizes with P407. Small molecule addition lowers thermal transition temperatures and increases the micelle size, while RP addition mitigates the decreases in modulus traditionally associated with small molecule incorporation. This fundamental understanding yields new strategies for tuning the mechanical and structural properties of the hydrogels, enabling design of drug-loaded formulations with ideal thermal transitions for a range of clinical applications.

Original languageEnglish (US)
Article number128246
Pages (from-to)128246
JournalColloids and Surfaces A: Physicochemical and Engineering Aspects
Volume638
DOIs
StatePublished - Apr 5 2022

Bibliographical note

Funding Information:
This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. CON-75851, Project 00074041. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. Research reported in this publication was supported by The National Institute on Deafness and Other Communication Disorders of the National Institutes of Health under award number R21DC019184-01A1. This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility, operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. SAXS experiments were carried out at Sector 5 of the Advanced Photon Source. The Sector 5 DuPont-Northwestern-Dow Collaborative Access Team (DND-CAT) was supported by E.I. DuPont de Nemours & Co. the Dow Chemical Company, and Northwestern University. Lab-source SAXS experiments were carried out at the Characterization Facility, University of Minnesota, which receives partial support from the NSF through the MRSEC (Award Number DMR-2011401) and the NNCI (Award Number ECCS-2025124) programs. The authors thank the Anton Paar VIP program for the rheometer used in this work. NMR instruments reported in this publication were supported by the Office of the Vice President of Research, College of Science and Engineering, and the Department of Chemistry at the University of Minnesota.

Funding Information:
This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. CON-75851, Project 00074041. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. Research reported in this publication was supported by The National Institute on Deafness and Other Communication Disorders of the National Institutes of Health under award number R21DC019184-01A1. This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility, operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. SAXS experiments were carried out at Sector 5 of the Advanced Photon Source. The Sector 5 DuPont-Northwestern-Dow Collaborative Access Team (DND-CAT) was supported by E.I. DuPont de Nemours & Co., the Dow Chemical Company, and Northwestern University. Lab-source SAXS experiments were carried out at the Characterization Facility, University of Minnesota, which receives partial support from the NSF through the MRSEC (Award Number DMR-2011401) and the NNCI (Award Number ECCS-2025124) programs. The authors thank the Anton Paar VIP program for the rheometer used in this work. NMR instruments reported in this publication were supported by the Office of the Vice President of Research, College of Science and Engineering, and the Department of Chemistry at the University of Minnesota.

Publisher Copyright:
© 2022 Elsevier B.V.

Keywords

  • Drug delivery
  • Hydrogel
  • Pluronic
  • Poloxamer
  • Self-assembly

How much support was provided by MRSEC?

  • Shared

PubMed: MeSH publication types

  • Journal Article

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