In Vitro and Ex Vivo Studies on the Absorption and Distribution of β-Cyclodextrin Polymer

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Polymer Chemistry

Background:

• Cyclodextrin (CD) polymers are increasingly recognized for their drug delivery potential.
• Limited data exists on the biological behavior of modified cyclodextrin polymers compared to native forms.

Purpose of the Study:

• To investigate the permeation and cellular uptake of epichlorohydrin-crosslinked β-cyclodextrin polymers.
• To evaluate these properties using a range of in vitro and ex vivo models.

Main Methods:

• Utilized fluorescently labeled β-cyclodextrin polymers.
• Performed membrane permeation studies with varying pore sizes.
• Assessed in vitro transport and cellular uptake using HaCaT, Caco-2, and TR146 cell lines.
• Conducted ex vivo permeation studies with skin, buccal, and intestinal tissues.

Main Results:

• Demonstrated size-dependent transport across synthetic membranes.
• Observed cell-line-specific intracellular distribution, with lysosomal accumulation in HaCaT and Caco-2 cells, but not TR146 cells.
• Confirmed tissue permeation, with significant accumulation in skin layers indicating dermal retention.
• Found strong correlations between in vitro and ex vivo skin and intestinal models.

Conclusions:

• β-cyclodextrin polymers exhibit complex, barrier-dependent transport characteristics.
• Differences in permeation and localization suggest multiple underlying transport mechanisms.
• These findings provide a basis for future research into the molecular mechanisms of polymer interaction.