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An enzyme-mediated controlled release system for curcumin based on cyclodextrin/cyclodextrin degrading enzyme.
Sahar Roozbehi1, Simin Dadashzadeh2, Reza H Sajedi1
1Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran 14115-154, Iran.
Enzyme and Microbial Technology
|February 5, 2021
Summary
This study introduces an enzyme-triggered system for controlled drug release. Maltogenic amylase (MAase) degrades beta-cyclodextrin (β-CD), releasing curcumin (CUR) for enhanced cancer cell targeting and apoptosis.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Enzyme Engineering
Background:
- Hydrophobic drugs like curcumin (CUR) exhibit poor water solubility, limiting their therapeutic efficacy.
- Controlled release systems are crucial for improving drug bioavailability and targeted delivery.
- Enzyme-responsive systems offer precise drug release mechanisms triggered by specific biological cues.
Purpose of the Study:
- To develop an enzyme-triggered drug delivery system for hydrophobic drugs using beta-cyclodextrin (β-CD) and maltogenic amylase (MAase).
- To investigate the controlled release of curcumin (CUR) from β-CD in the presence of MAase.
- To evaluate the enhanced cellular uptake, anti-proliferative, cytotoxic, and apoptotic effects of the CUR/β-CD/MAase system on cancer cells.
Main Methods:
- Formation and characterization of curcumin (CUR) inclusion complexes with beta-cyclodextrin (β-CD) using fluorescence and FTIR spectroscopy.
- In vitro drug release studies monitoring CUR release kinetics in the presence and absence of maltogenic amylase (MAase).
- Cellular uptake studies using fluorescence microscopy and apoptosis assays (acridine orange/ethidium bromide, Annexin V-PE/7-AAD) on MCF-7 and Huh-7 cancer cells.
Main Results:
- Curcumin (CUR) was successfully encapsulated in β-CD with ~30% efficiency.
- MAase triggered 100% release of CUR from β-CD within one hour due to β-CD degradation.
- The β-CD-CUR/MAase system demonstrated significantly enhanced cellular uptake, lower IC50 values, and increased cytotoxic and apoptotic effects compared to free CUR or β-CD-CUR.
Conclusions:
- The developed enzyme-mediated system enables triggered release of hydrophobic drugs like CUR in response to MAase.
- This system shows potential for improved cancer therapy by enhancing drug delivery and efficacy.
- The β-CD degradation by MAase is the key mechanism for controlled drug release and enhanced therapeutic outcomes.
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