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Abstract

Background

Subcutaneous administration is preferred for its advantages over other administering routes

but requires understanding the interactions of drug molecules with interstitial fluid compo-

nents. One of those components is albumin, an essential transport protein for endogenous and

exogenous compounds. Albumin has two major drug-binding sites and over seven fatty acid-

binding sites. Its flexible structure at physiological pH allows ligand binding to induce con-

formational changes, which can modulate the binding of another ligand to albumin.

Methods and objective

This study examines the binding of two drugs, chlorpromazine and warfarin, to albumin us-

ing fluorescence spectroscopy, in the presence and absence of interstitial fluid components,

such as long- and medium-chain fatty acids and biopolymer. Previous studies have focused

on either fatty acids, polymers, or drugs in relation to albumin interactions. This in-vitro

study investigates how the presence of fatty acids and biopolymers affects drug-albumin in-

teractions during subcutaneous administration.

Results and Discussion

Medium-chain fatty acids, such as sodium decanoate and sodium laurate, compete both

drugs in binding to HSA. Additionally, longer fatty acid chains exhibit stronger competition

with drug molecules. Long-chain fatty acids more effectively displace chlorpromazine than

warfarin, as warfarin binds more strongly to albumin. Biopolymers appear to facilitate drug

binding by inducing structural changes that open up albumin.

Conclusion

These findings suggest that the presence of fatty acids and biopolymers can modulate drug

binding to albumin, potentially impacting drug distribution and efficacy.