Optimizing the synthesis conditions of CaAl-layered double hydroxide and poly (3-hydroxybutyrate)/CaAl-LDH nanocomposite for potential use in antibacterial drug delivery

Abstract

Calcium aluminum layered double hydroxide (CaAl-LDH) has gained significance for drug delivery applications due to its multiple advantages, including high drug-loading capacity, pH sensitivity, biocompatibility, high acceptable intake values of metal ions, and its ability to provide sustained release of the intercalated drug. In this study, pristine CaAl-LDH was synthesized by co-precipitation method at different pH values (9 and 10) and aging times (16 and 24 h) to obtain LDH with higher d-spacing, which is beneficial for achieving a high drug loading efficiency. Ofloxacin (OFX), an antibiotic drug, was loaded into CaAl-LDH via regeneration (CaAl-LDH-OFX(RG)) and co-precipitation (CaAl-LDH-OFX(CPT)) methods, and achieved drug loading of 28.3% and 36.5%, respectively. The release behavior of OFX from CaAl-LDH-OFX(RG) and CaAl-LDH-OFX(CPT) formulations was examined in simulated conditions representing the gastrointestinal tract. CaAl-LDH-OFX(RG) showed less initial burst release of OFX compared to CaAl-LDH-OFX(CPT) in acidic as well as neutral pH conditions. In order to overcome the degradation of the drug before reaching the target site, CaAl-LDH-OFX(RG) was reinforced at 1, 3, and 5 wt% in poly (3-hydroxybutyrate) (PHB) matrix by sonication-assisted solution casting method. The PHB-based nanocomposites were characterized by XRD, FESEM, TGA, and FTIR analyses. FESEM characterization of PHB-based films loaded with 3 wt% of CaAl-LDH-OFX(RG) revealed compact morphology without any aggregate formation. Moreover, PHB/3CaAl-LDH-OFX(RG) films demonstrated sustained release of OFX at pH 1.2 (95.60% in 96 h), pH 6.8 (78% in 113 h), and pH 7.4 (40.90% in 107 h). The promising potential of PHB-based formulations for antibacterial drug delivery systems was confirmed by their significant antibacterial activity against Escherichia coli and Staphylococcus aureus. Highlights: pH and aging time influence the structural characteristics of pristine CaAl-LDH. Ofloxacin loaded CaAl-LDH prepared by co-precipitation and regeneration methods. Sustained release of ofloxacin from poly (3-hydroxybutyrate)-based formulation. Poly (3-hydroxybutyrate)-based formulations exhibit excellent antibacterial activity.