Optimizing the synthesis conditions of <scp>CaAl</scp>‐layered double hydroxide and poly (3‐hydroxybutyrate)/<scp>CaAl</scp>‐<scp>LDH</scp> 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.