Posted by A recent study provides new insights into the absorption, permeation, and tissue distribution of an epichlorohydrin-crosslinked β-cyclodextrin polymer, a promising excipient and drug delivery carrier whose biological fate has remained insufficiently characterized. While the pharmacokinetic properties of native cyclodextrins are well documented, significantly less is known about cyclodextrin polymers, despite their increasing use in pharmaceutical formulations. To address this knowledge gap, researchers investigated the transport and cellular uptake of a fluorescently labelled β-cyclodextrin polymer using a combination of synthetic membrane systems, cell culture models, and ex vivo biological tissues. The study first examined permeation across synthetic membranes with different pore sizes. Results demonstrated a strong size-dependent transport pattern, confirming that membrane structure plays a critical role in regulating polymer passage. Cellular uptake experiments were then conducted on three widely used barrier models: HaCaT keratinocytes, Caco-2 intestinal epithelial cells, and TR146 buccal epithelial cells. Interestingly, the polymer exhibited markedly different intracellular behaviour depending on the cell type. In HaCaT and Caco-2 cells, the polymer accumulated within lysosomes, suggesting active cellular internalization followed by intracellular trafficking. In contrast, no intracellular accumulation was detected in TR146 cells, indicating substantial differences in the interaction of the polymer with various biological barriers. The researchers also evaluated polymer permeation through excised skin, buccal, and intestinal tissues. The ex vivo studies confirmed that the β-cyclodextrin polymer is capable of penetrating biological tissues; however, the most pronounced accumulation was observed within skin layers. This finding suggests that dermal retention may represent a dominant transport pathway, a characteristic that could be particularly advantageous for topical and transdermal drug delivery strategies. An important outcome of the work was the identification of strong correlations between selected in vitro and ex vivo models, especially for skin and intestinal tissues. These correlations support the predictive value of carefully designed cell-based systems and may help reduce the reliance on more complex biological models during formulation development.
Overall, the findings highlight that β-cyclodextrin polymers display complex, barrier-dependent transport properties that vary according to membrane characteristics, tissue type, and cellular environment. The observed differences in permeation and intracellular localization suggest that multiple transport mechanisms are involved in their biological behaviour. The study provides an important foundation for future investigations aimed at elucidating the molecular mechanisms governing the uptake and transport of cyclodextrin polymers. Such knowledge will support the rational design of advanced cyclodextrin-based drug delivery systems and help optimize their performance in topical, mucosal, and oral pharmaceutical applications.
Révész, R.; Mengenli, A.D.; Rusznyák, Á.; Kajtár, R.; Lekli, I.; Bácskay, I.; Haimhoffer, Á. In Vitro and Ex Vivo Studies on the Absorption and Distribution of β-Cyclodextrin Polymer. Pharmaceutics 2026, 18, 854. https://doi.org/10.3390/pharmaceutics18070854
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Figure 4. Investigation of the cellular distribution of fluorescently labelled beta-cyclodextrin polymer (FITC-NH-BCDSP) in HaCaT cells. The labelled cyclodextrin molecule appeared in HaCaT cells and in vesicles in the cytoplasm in fluorescent microscope images (green pixels—FITC-NH-BCDSP, red pixels—LysoTracker®, blue pixels—cell nuclei). Scale bar = 20 µm.