Engineering atorvastatin loaded Mg-Mn/LDH nanoparticles and their composite with PLGA for bone tissue applications

The impact of mixing method in conventional co-precipitation synthesis of layered double hydroxides (LDHs), on particle size, size distribution and drug loading capacity is reported. Synthesis of Mg (II)/Mn (III)-LDH nano-platelets was performed at constant pH using three different mixing systems, magnetic stirrer, mechanical mixer, and homogenizer at ambient temperature and a fixed Mg/Mn ratio of 3/1. The LDH characterization results showed that mechanical mixing and homogenization lead to production of very fine LDH nano-platelets (about 90-140 nm), with narrow particle size distribution. Amount of the intercalated drug was determined as about 60% and showed a significant increase in loading capacity of the LDH through homogenization and mechanical mixing compared to that of the magnetic stirring (about 35%). Our results also showed that in LDH preparation via co-precipitation, the mixing system plays a more influential role in particle size, size distribution, and drug loading control, than the mixing speed of each system. Drug loaded-LDH/PLGA composites were prepared via electrospinning to afford a bioactive/osteoinductive scaffold. A remarkable degree of cell viability on the scaffolds (drug-loaded-LDH/PLGA composite) was confirmed using MTT assay. Osteogenic differentiation of human ADMSCs, as shown by alkaline phosphatase activity and Alizarin Red staining assays, indicated that the scaffold with 5% drug loaded LDH(Mn-Mg-LDH/PLGA/AT5%) induced a remarkably higher level of the markers compared to the PLGA scaffold and therefore, it could be a valuable candidate for bone tissue engineering applications.