1. Cellular delivery and enhanced anticancer activity of berberine complexed with a cationic derivative of γ-cyclodextrin.
- Author
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Popiołek I, Niziołek A, Kamiński K, Kwolek U, Nowakowska M, and Szczubiałka K
- Subjects
- Animals, Antineoplastic Agents chemical synthesis, Cations chemical synthesis, Cations chemistry, Cations pharmacology, Cell Line, Cell Proliferation drug effects, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Mice, Molecular Structure, Structure-Activity Relationship, gamma-Cyclodextrins chemical synthesis, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Drug Delivery Systems, gamma-Cyclodextrins chemistry, gamma-Cyclodextrins pharmacology
- Abstract
A cationic derivative of γ-cyclodextrin (GCD) modified with propylenediamine (PDA) was synthesized. It was shown that the derivative (GCD-PDA) is mucoadhesive and resistant to the digestion with ∝-amylase indicating that it may constitute an efficient oral delivery vehicle. GCD-PDA formed an inclusion complex with berberine (BBR), an alkaloid displaying a multitude of beneficial physiological effects. The complexed BBR penetrates a lipid membrane easier than the free one. Both uncomplexed BBR and that complexed with GCD-PDA was delivered to normal (NMuMG) and cancerous (4T1) murine mammary gland cells. In the normal cells both free and complexed BBR was homogeneously dispersed in the cytoplasm and was nontoxic up to 131 μM. In the cancerous cells uncomplexed BBR was also homogeneously dispersed but it was toxic to about 25% of cells at 131 μM, while the GCD-PDA/BBR complex was preferably localized in lysosomes and its toxicity doubled at this concentration compared to that of free BBR. Moreover, free BBR and GCD-PDA/BBR showed even more efficient inhibitory effect against murine melanoma (B16-F10) cells than against 4T1 cells., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
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