Drug–protein interactions in micellar media: Thermodynamic aspects

• Binding of naproxen and diclofenac to serum albumin is modified when delivered from micelles.
• Integrity of binding sites is not altered when drug binding occurs under micellar conditions.
• Naproxen mainly interacts on the surface of the micelles.
• Diclofenac sodium partitions in palisade layer of the micelles.
• Micelles assisted drug–protein interactions are modified based on hydrophobicity of the drug.

Devising directions for surfactant assisted effective controlled release of drugs requires a quantitative and qualitative understanding of the drug–protein, drug–surfactant, and surfactant–protein interactions. In this work, the effect of micellar environment on the binding of naproxen and diclofenac sodium with bovine serum albumin has been studied. The isothermal titration calorimetric (ITC) results suggest that the binding of naproxen is reduced with the protein when it is delivered from micellar media. However, the binding is observed to be strengthened for diclofenac sodium. The differential scanning calorimetric results suggest that the integrity of the binding sites is not altered under the employed micellar conditions. The ITC results further suggest that the numbers of naproxen and diclofenac sodium molecules partitioning/binding per micelle of HTAB are 15 and 38, respectively. In the micelles, naproxen is restricted to the surface of the micelles whereas diclofenac sodium is able to partition in the palisade layers. A detailed understanding of the energetics of the drug–protein interactions under different conditions helps in devising directions for effective drug delivery. The ITC and DSC results have shown that the micelles assisted drug–protein interactions are modified depending on the hydrophobic content of the drug.

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