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Crystallization of supersaturated PEG-b-PLA for the production of drug-loaded polymeric micelles.

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Title: Crystallization of supersaturated PEG-b-PLA for the production of drug-loaded polymeric micelles.
Authors: Rasoulianboroujeni, Morteza1 (AUTHOR), Kang, Rae Hyung1,2 (AUTHOR), Klukas, Maraya1 (AUTHOR), Kwon, Glen S.1 (AUTHOR) glen.kwon@wisc.edu
Source: Journal of Controlled Release. Apr2025, Vol. 380, p457-468. 12p.
Subjects: Supersaturated solutions, Drug delivery systems, Particle size distribution, Cytotoxins, Lactic acid, Copolymer micelles, Molecular weights
Abstract: In this study, we propose the "crystallization from supersaturated solution" method for producing drug-loaded polymeric micelles. This method involves the formation of solid drug-encapsulating crystals of a diblock copolymer through isothermal crystallization from a supersaturated solution of the copolymer in low molecular weight PEGs containing the drug, followed by dissolution of the crystals to obtain drug-loaded micelles. We fabricated and characterized micelles loaded with several model drugs (paclitaxel, rapamycin, and docetaxel) and their oligo(lactic acid) 8 -prodrugs using PEG 4kDa - b -PLA 2.2kDa as the micelle-forming copolymer and PEGs of varying molecular weights (200, 400, and 600 Da) as solvents. Our findings indicate that the molecular weight of the solvent PEG and the target drug loading significantly influence the physicochemical properties of the resulting micelles, including loading efficiency and particle size distribution. Micelles produced with PEG200 as the solvent exhibited the highest loading efficiency, followed by those made with PEG600 and PEG400 for all the drugs and prodrugs tested. Increasing the target drug loading enhanced both the loading efficiency and average particle size across all formulations. Furthermore, prodrug-loaded micelles showed higher loading efficiency and improved stability in aqueous solutions compared to their parent drug counterparts. Crystals encapsulating both parent drugs and prodrugs could be stored at room temperature for extended periods, producing micelles with no significant differences in loading efficiency and particle size distribution compared to freshly prepared micelles. Additionally, the crystals demonstrated a rapid dissolution rate, forming uniform micelles after just 5 s of hydration and agitation. Cytotoxicity studies against 4 T1 and MDA-MB-231 breast cancer cell lines revealed that the molecular weight of the PEG used as the solvent impacts the cytotoxicity of the resulting micelles, with those produced using PEG200 displaying the highest cytotoxicity, followed by PEG400 and PEG600. Overall, the crystallization from supersaturated solution method proves to be an effective platform for prolonged storage and rapid formation of stable, drug-loaded polymeric micelles. It has the potential to eliminate the need for freeze-drying in the formulation and storage of drug-loaded polymeric micelles. These findings highlight the method's potential for advancing drug delivery systems, particularly for the solubilization of hydrophobic drugs using micellar formulations. [Display omitted] • The "Crystallization from Supersaturated Solution" enables the loading of various drugs into polymeric micelles. • This method allows prolonged storage of drug-loaded micelles in solid form, eliminating the need for freeze-drying. • Solvent molecular weight and drug concentrationinfluence micelle properties and cytotoxicity. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Controlled Release is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
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Header DbId: egs
DbLabel: Engineering Source
An: 183703461
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
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  Label: Title
  Group: Ti
  Data: Crystallization of supersaturated PEG-b-PLA for the production of drug-loaded polymeric micelles.
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  Data: <searchLink fieldCode="AR" term="%22Rasoulianboroujeni%2C+Morteza%22">Rasoulianboroujeni, Morteza</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kang%2C+Rae+Hyung%22">Kang, Rae Hyung</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Klukas%2C+Maraya%22">Klukas, Maraya</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kwon%2C+Glen+S%2E%22">Kwon, Glen S.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> glen.kwon@wisc.edu</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Controlled+Release%22">Journal of Controlled Release</searchLink>. Apr2025, Vol. 380, p457-468. 12p.
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  Data: <searchLink fieldCode="DE" term="%22Supersaturated+solutions%22">Supersaturated solutions</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+delivery+systems%22">Drug delivery systems</searchLink><br /><searchLink fieldCode="DE" term="%22Particle+size+distribution%22">Particle size distribution</searchLink><br /><searchLink fieldCode="DE" term="%22Cytotoxins%22">Cytotoxins</searchLink><br /><searchLink fieldCode="DE" term="%22Lactic+acid%22">Lactic acid</searchLink><br /><searchLink fieldCode="DE" term="%22Copolymer+micelles%22">Copolymer micelles</searchLink><br /><searchLink fieldCode="DE" term="%22Molecular+weights%22">Molecular weights</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: In this study, we propose the "crystallization from supersaturated solution" method for producing drug-loaded polymeric micelles. This method involves the formation of solid drug-encapsulating crystals of a diblock copolymer through isothermal crystallization from a supersaturated solution of the copolymer in low molecular weight PEGs containing the drug, followed by dissolution of the crystals to obtain drug-loaded micelles. We fabricated and characterized micelles loaded with several model drugs (paclitaxel, rapamycin, and docetaxel) and their oligo(lactic acid) 8 -prodrugs using PEG 4kDa - b -PLA 2.2kDa as the micelle-forming copolymer and PEGs of varying molecular weights (200, 400, and 600 Da) as solvents. Our findings indicate that the molecular weight of the solvent PEG and the target drug loading significantly influence the physicochemical properties of the resulting micelles, including loading efficiency and particle size distribution. Micelles produced with PEG200 as the solvent exhibited the highest loading efficiency, followed by those made with PEG600 and PEG400 for all the drugs and prodrugs tested. Increasing the target drug loading enhanced both the loading efficiency and average particle size across all formulations. Furthermore, prodrug-loaded micelles showed higher loading efficiency and improved stability in aqueous solutions compared to their parent drug counterparts. Crystals encapsulating both parent drugs and prodrugs could be stored at room temperature for extended periods, producing micelles with no significant differences in loading efficiency and particle size distribution compared to freshly prepared micelles. Additionally, the crystals demonstrated a rapid dissolution rate, forming uniform micelles after just 5 s of hydration and agitation. Cytotoxicity studies against 4 T1 and MDA-MB-231 breast cancer cell lines revealed that the molecular weight of the PEG used as the solvent impacts the cytotoxicity of the resulting micelles, with those produced using PEG200 displaying the highest cytotoxicity, followed by PEG400 and PEG600. Overall, the crystallization from supersaturated solution method proves to be an effective platform for prolonged storage and rapid formation of stable, drug-loaded polymeric micelles. It has the potential to eliminate the need for freeze-drying in the formulation and storage of drug-loaded polymeric micelles. These findings highlight the method's potential for advancing drug delivery systems, particularly for the solubilization of hydrophobic drugs using micellar formulations. [Display omitted] • The "Crystallization from Supersaturated Solution" enables the loading of various drugs into polymeric micelles. • This method allows prolonged storage of drug-loaded micelles in solid form, eliminating the need for freeze-drying. • Solvent molecular weight and drug concentrationinfluence micelle properties and cytotoxicity. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Controlled Release is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1016/j.jconrel.2025.02.009
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 12
        StartPage: 457
    Subjects:
      – SubjectFull: Supersaturated solutions
        Type: general
      – SubjectFull: Drug delivery systems
        Type: general
      – SubjectFull: Particle size distribution
        Type: general
      – SubjectFull: Cytotoxins
        Type: general
      – SubjectFull: Lactic acid
        Type: general
      – SubjectFull: Copolymer micelles
        Type: general
      – SubjectFull: Molecular weights
        Type: general
    Titles:
      – TitleFull: Crystallization of supersaturated PEG-b-PLA for the production of drug-loaded polymeric micelles.
        Type: main
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          Name:
            NameFull: Rasoulianboroujeni, Morteza
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            NameFull: Kang, Rae Hyung
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            NameFull: Klukas, Maraya
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            NameFull: Kwon, Glen S.
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            – D: 10
              M: 04
              Text: Apr2025
              Type: published
              Y: 2025
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              Value: 01683659
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              Value: 380
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            – TitleFull: Journal of Controlled Release
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