Construction and characterization of self-assembled curcumin nanoparticles and composite microneedle delivery system...

In the current field of drug delivery systems, nanomedicines have attracted extensive attention due to their remarkable potential to enhance the solubility, stability, and delivery efficiency of poorly soluble drugs. Among them, stabilizers play a pivotal role in maintaining the physical stability of nanoparticles and optimizing their delivery performance. Therefore, the rational selection of appropriate stabilizers is a critical step in the preparation of high-quality nanopharmaceuticals. In this study, curcumin (CUR) was selected as a model drug, and molecular dynamics (MD) simulations were employed to analyze the self-assembly behavior of molecules and virtually screen suitable stabilizers for nanosuspensions. By systematically evaluating the interaction energies, binding patterns, and dynamic stability between CUR and various stabilizer combinations through computational modeling, the combination of polyvinylpyrrolidone (PVP K30) and polyvinyl alcohol (PVA) was identified as the optimal stabilizer system. Based on this, curcumin nanosuspensions (CUR-NS) were prepared using Hummer acoustic resonance technology, and formulation parameters were optimized using a Design of Experiments (DoE) approach. The final CUR-NS exhibited a mean particle size of 107.36 ± 2.39 nm, a PDI of 0.215 ± 0.019, and a zeta potential of -46.81 ± 2.51 mV, indicating improved solubility and physical stability of CUR. To achieve more efficient transdermal delivery, a dual-layer composite microneedle system (CUR-NS-MN) loaded with CUR-NS was further developed using a 1:1 mass ratio of PVP K30 to PVA as the molding matrix. The resulting microneedles exhibited excellent mechanical strength (fracture force: 558 gf/needle) and could completely penetrate artificial skin without breakage. Confocal laser scanning microscopy (CLSM) demonstrated uniform distribution of CUR within the needle body. Transdermal release studies showed that the system achieved sustained release over 24 h, exhibiting favorable controlled-release characteristics. In conclusion, this study not only established an efficient and accurate virtual screening strategy for stabilizer selection but also developed a high-performance CUR-NS-loaded microneedle platform, providing a novel and scalable solution for transdermal delivery of poorly soluble drugs.