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Pickering double emulsions stabilized by acylated cellulose nanocrystals for oral co-delivery of macromolecules and permeation enhancers.

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Title: Pickering double emulsions stabilized by acylated cellulose nanocrystals for oral co-delivery of macromolecules and permeation enhancers.
Authors: Bertsch, Pascal1 (AUTHOR) pascal.bertsch@unifr.ch, Frøslev, Patrick1 (AUTHOR), Currie, Jonathan2 (AUTHOR), Carrière, Frédéric3 (AUTHOR), Müllertz, Anette2 (AUTHOR), Nielsen, Hanne Mørck1 (AUTHOR) hanne.morck@sund.ku.dk
Source: Journal of Colloid & Interface Science. Dec2025:Part 1, Vol. 700, pN.PAG-N.PAG. 1p.
Subjects: Cellulose nanocrystals, Intestinal absorption, Pickering emulsions, Oral drug administration, Drug delivery systems, Macromolecules
Abstract: Double emulsions are potential oral delivery systems for the simultaneous administration of hydrophilic drugs and hydrophobic permeation enhancers to enable effective intestinal absorption of macromolecular drugs. Emulsions stabilized by solid particles, i.e. , Pickering stabilizers, have shown potential to form gastric-stable emulsions that can protect their cargo from release under gastric conditions. Here, we use acylated cellulose nanocrystals to facilitate the formation of stable double emulsions for intestinal drug delivery. Water-in-oil-in-water double emulsions were obtained by a two-step emulsification process and found to be colloidally stable over 6 months allowing permanent encapsulation of a high molecular weight compound (4 kDa fluorescein isothiocyanate-labelled dextran, FD4) in the inner water phase at >90 % encapsulation efficiency. Exposure to simulated gastric conditions and gastric lipase did not affect the emulsion structure or trigger FD4 release. Double emulsions underwent a pronounced restructuring under simulated intestinal conditions due to the presence of bile, yet without triggering excessive FD4 release (<10 %). Digested emulsions reduced the transepithelial electrical resistance of an intestinal in vitro Caco-2 cell culture model by hydrolysis of the emulsion oil phase into medium chain fatty acids that act as intrinsic permeation enhancers. The double emulsions facilitated permeation of FD4 across the intestinal in vitro model at similar levels as non-formulated FD4 and C10. Hence, double Pickering emulsions stabilized by acylated cellulose nanocrystals comprise a novel gastric stable oral delivery system that can co-deliver large hydrophilic macromolecules and permeation enhancers to the small intestine towards effective intestinal absorption. [Display omitted] • Cellulose nanocrystal modification facilitates Pickering double emulsion stabilization. • Double Pickering emulsions remain colloidally stable for months due to gelation. • Double emulsions can permanently encapsulate macromolecules (4 kDa FITC-dextran). • FITC-dextran remains encapsulated under simulated gastric and intestinal conditions. • Double emulsions facilitate FITC-dextran permeation across model Caco-2 epithelium. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Colloid & Interface Science is the property of Academic Press Inc. 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.)
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  Data: Pickering double emulsions stabilized by acylated cellulose nanocrystals for oral co-delivery of macromolecules and permeation enhancers.
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  Data: Double emulsions are potential oral delivery systems for the simultaneous administration of hydrophilic drugs and hydrophobic permeation enhancers to enable effective intestinal absorption of macromolecular drugs. Emulsions stabilized by solid particles, i.e. , Pickering stabilizers, have shown potential to form gastric-stable emulsions that can protect their cargo from release under gastric conditions. Here, we use acylated cellulose nanocrystals to facilitate the formation of stable double emulsions for intestinal drug delivery. Water-in-oil-in-water double emulsions were obtained by a two-step emulsification process and found to be colloidally stable over 6 months allowing permanent encapsulation of a high molecular weight compound (4 kDa fluorescein isothiocyanate-labelled dextran, FD4) in the inner water phase at &gt;90 % encapsulation efficiency. Exposure to simulated gastric conditions and gastric lipase did not affect the emulsion structure or trigger FD4 release. Double emulsions underwent a pronounced restructuring under simulated intestinal conditions due to the presence of bile, yet without triggering excessive FD4 release (&lt;10 %). Digested emulsions reduced the transepithelial electrical resistance of an intestinal in vitro Caco-2 cell culture model by hydrolysis of the emulsion oil phase into medium chain fatty acids that act as intrinsic permeation enhancers. The double emulsions facilitated permeation of FD4 across the intestinal in vitro model at similar levels as non-formulated FD4 and C10. Hence, double Pickering emulsions stabilized by acylated cellulose nanocrystals comprise a novel gastric stable oral delivery system that can co-deliver large hydrophilic macromolecules and permeation enhancers to the small intestine towards effective intestinal absorption. [Display omitted] • Cellulose nanocrystal modification facilitates Pickering double emulsion stabilization. • Double Pickering emulsions remain colloidally stable for months due to gelation. • Double emulsions can permanently encapsulate macromolecules (4 kDa FITC-dextran). • FITC-dextran remains encapsulated under simulated gastric and intestinal conditions. • Double emulsions facilitate FITC-dextran permeation across model Caco-2 epithelium. [ABSTRACT FROM AUTHOR]
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  Data: &lt;i&gt;Copyright of Journal of Colloid &amp; Interface Science is the property of Academic Press Inc. and its content may not be copied or emailed to multiple sites without the copyright holder&#39;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.&lt;/i&gt; (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1016/j.jcis.2025.138363
    Languages:
      – Code: eng
        Text: English
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        PageCount: 1
        StartPage: N.PAG
    Subjects:
      – SubjectFull: Cellulose nanocrystals
        Type: general
      – SubjectFull: Intestinal absorption
        Type: general
      – SubjectFull: Pickering emulsions
        Type: general
      – SubjectFull: Oral drug administration
        Type: general
      – SubjectFull: Drug delivery systems
        Type: general
      – SubjectFull: Macromolecules
        Type: general
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      – TitleFull: Pickering double emulsions stabilized by acylated cellulose nanocrystals for oral co-delivery of macromolecules and permeation enhancers.
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              Text: Dec2025:Part 1
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