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Celecoxib Encapsulation in β-Casein Micelles: Structure, Interactions, and Conformation
Tanya Turovsky1, Rafail Khalfin2, Shifi Kababya3
1†Russell Berrie Nanotechnology Institute, Technion - Israel Institute of Technology, Haifa 3200003, Israel.
Beta-casein micelles effectively encapsulate drugs, improving oral bioavailability. These protein-drug formulations demonstrate excellent stability, even after freeze-drying and rehydration, showing promise for pharmaceutical delivery.
Area of Science:
- Biochemistry
- Materials Science
- Pharmaceutical Sciences
Background:
- Beta-casein is an intrinsically unstructured protein with amphiphilic properties at neutral pH.
- Unstructured proteins typically remain monomeric, but beta-casein self-assembles into core-shell micelles.
- These micelles show potential as carriers for oral drug delivery of poorly water-soluble drugs.
Purpose of the Study:
- To provide detailed physicochemical insights into beta-casein-drug formulations.
- To characterize drug conformation, packing, and aggregation state in both solution and dry forms.
- To evaluate protein-drug interactions, nanostructure, morphology, and physical stability.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy for drug-protein interactions and conformation.
- Small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cryo-TEM) for nanostructural analysis.
- Dynamic light scattering (DLS), turbidity measurements, and visual observations for stability and structural characterization.
Main Results:
- NMR indicated strong drug-protein interactions and a noncrystalline drug conformation, enhancing solubility.
- SAXS and cryo-TEM revealed drug loading leads to denser, puffier spheroidal micelles.
- Formulations maintained properties through freeze-drying and rehydration, ensuring long-term stability.
Conclusions:
- Beta-casein micelles are a promising formulation for oral delivery of poorly soluble drugs.
- The protein-drug interactions improve drug conformation and bioavailability.
- The developed formulation exhibits robust physical and chemical stability for pharmaceutical applications.
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