(W1230-07-43) Development and Optimization of Curcumin-Loaded Polycaprolactone Nanoparticles Using Smart Technology

Purpose: The purpose of this study was to develop and explore the possibilities of extrusion-based printing of Curcumin loaded PCl particles, using a novel technology, SMART (Sprayed Multi Adsorbent-droplet Reposing technology). The aim was to study the effects of printing parameters on particle size and PDI on the PCL-Curcumin particles, alongside improving the encapsulation efficiency. SMART is a novel technology that combines both extrusion-based printing with the solvent evaporation technique to fabricate small-molecule drugs, peptides, and proteins. SMART employs shear force exerted by the printing nozzle rather than using sonication energy to generate smaller emulsion droplets in a single step. This helps formulate thermally sensitive drugs without having to subject them to high mechanical stress during the formulation process. Furthermore, the applied shear force during the printing process is controllable since the emulsion is extruded through the nozzle under preset printing conditions.

Methods: Initially, a Design of Experiments (DoE) approach was employed to optimize the SMART process parameters using placebo formulations.The independent variables included printing pressure (300, 400, 500, and 600 kPa) and gauze diameter (0.21, 0.26, and 0.52 mm), while the dependent variables were particle size and polydispersity index (PDI). Placebo nanoparticles were prepared by spraying an organic phase (1% w/v PCL in DCM) onto an aqueous phase (0.5% or 1% w/v PVA) using a BioX extrusion-based 3D printer. The resulting emulsions underwent solvent evaporation and were lyophilized for 72 hours. Particle size and PDI were measured using dynamic light scattering (DLS). Based on the DoE analysis, optimal parameters yielding desirable particle size and PDI were identified. These optimized conditions were then applied to formulate curcumin-loaded nanoparticles. The organic phase for these formulations consisted of 1% w/v PCL and 1% w/v curcumin in DCM, while the aqueous phase contained varying concentrations of PVA (0.5% to 2.5% w/v). The emulsions were processed similarly to the placebos, followed by lyophilization. The resulting nanoparticles were characterized for particle size, PDI, zeta potential, encapsulation efficiency (EE), and yield.

Results: The DoE analysis revealed that both printing pressure and nozzle diameter significantly influenced particle size and PDI. Higher pressures and larger nozzle diameters tended to produce smaller particles with lower PDI values. For instance, at 600 kPa pressure and 0.52 mm nozzle diameter, the particle size achieved was 872 ± 50.4 nm with a PDI of 0.856. Formulations with varying PVA concentrations demonstrated that increasing PVA concentration led to smaller particle sizes and lower PDI values. Specifically, formulations with 2% and 2.5% PVA resulted in particle sizes of approximately 134 nm and PDI values below 0.1. Encapsulation efficiencies ranged from 97.3% to 99.8%, indicating effective curcumin loading within the PCL matrix. The yield of nanoparticles varied between 84.7% and 100%, demonstrating the efficiency of the SMART process. Zeta potential measurements ranged from -11.5 mV to -18 mV, suggesting moderate stability of the nanoparticle suspensions.

Conclusion: The SMART technology effectively produced curcumin-loaded PCL nanoparticles with controlled particle size, low PDI, high encapsulation efficiency, and substantial yield, all without the application of heat or sonication. The ability to fine-tune process parameters allows for the customization of nanoparticle characteristics, making SMART a promising method for formulating thermosensitive drugs. This approach holds potential for scalable and continuous manufacturing of nanoparticle-based drug delivery systems.


Particle size, PDI, and ZP for various placebos during process optimization


Formulation Composition of SMART curcumin nanoparticles


Characterization Studies of SMART curcumin nanoparticles