Chain-Length-Dependent Anionic Surfactant Modification of Halloysite Nanotubes for Enhanced Levofloxacin Loading and Sustained Release

Halloysite nanotubes (HNTs) are hollow silicate nanotubes, ideal for drug delivery. In this work, we report a chain-length-dependent surfactant modification strategy to tailor the release kinetics of levofloxacin (LEV) from HNTs. Two types of anionic surfactants, sodium dodecyl sulfate (SDS) and sodium hexadecyl sulfonate (SHS), were selected to modify HNT and prepare two new drug carriers. LEV was used as the model drug, and its sustained release behavior was studied in simulated gastric fluid (pH [Formula: see text] 1.2) after drug loading. SEM images show that organic modification does not affect the microstructure of the HNT. Thermogravimetric analysis reveals SDS-HNT exhibits greater weight loss than SHS-HNT or HNT, indicating superior SDS adsorption. This stems from SHS’s lower solubility and longer hydrophobic chain hindering cavity loading. FT-IR results indicate that LEV is mainly immobilized on modified HNT through electrostatic attraction and hydrophobic interactions. Quantitatively, the modified carriers demonstrate significantly enhanced drug loading capacity: SDS-HNT achieves a maximum loading of 18.5[Formula: see text]wt.%, a 1.9-fold improvement over pristine HNT (9.7[Formula: see text]wt.%), while SHS-HNT reaches 22.3[Formula: see text]wt.%, representing a 2.3-fold increase. Drug release studies show that after 24[Formula: see text]h, SDS-HNT and SHS-HNT release 98.24% and 95.62% of their loaded LEV, respectively, compared to only 85.53% release from unmodified HNT. The release kinetics for all samples follow the Ritger–Peppas model. Combined with BET surface area analysis, the results indicate that surfactant modification, particularly with SHS, creates more accessible pore domains and alters surface chemistry. This transformation turns HNT from a carrier with slow and incomplete release into an efficient system enabling rapid and near-total drug release by reducing diffusion barriers and drug-carrier binding affinity. This study demonstrates that surfactant chain length and headgroup chemistry are critical levers for tuning the drug release performance of halloysite nanotube (HNT) carriers.