Optimizing nanoliposomal formulations: Assessing factors affecting entrapment efficiency of curcumin-loaded liposomes...

Curcumin faces challenges in clinical applications due to its low bioavailability and poor water solubility. Liposomes have emerged as a promising delivery system for curcumin. This study aims to apply ensemble learning, a machine learning technique, to determine the most effective experimental conditions for formulating stable curcumin-loaded liposomes with a high entrapment efficiency (EE).

Two liposomal formulations composed of HSPC:DPPG:Chol:DSPE-mPEG2000 and HSPC:Chol:DSPE-mPEG2000 at 55:5:35:5 and 55:40:5 M ratios, respectively, were prepared using the remote loading method, and their particle size and polydispersity index (PDI) were determined using Dynamic Light Scattering. To model the impact of five factors (molar ratios, particle size, sonication time, pH, and PDI) on EE%, the Least-squares boosting (LSBoost) ensemble learning algorithm was employed due to its capability to effectively handle nonlinear and non-stationary problems. The implementation and optimization of LSBoost were performed using MATLAB R2020a. The dataset was randomly split into training and testing sets, with 70% allocated for training. The mean absolute error (MAE) was used as the cost function to evaluate model performance. Additionally, a novel approach was employed to visualize the results using 3D plots, facilitating practical interpretation.

The optimal model exhibited an MAE of 3.61, indicating its robust predictive capability. The study identified several optimal conditions for achieving the highest EE value of 100%. However, to ensure both the highest EE value and a suitable particle size, it is recommended to set the following conditions: a molar ratio of 55:5:35:5, a PDI within the range of 0.09-0.13, a particle size of approximately 130 nm, a sonication time of 30 min, and a pH within the range of 7.2-8. It is worth mentioning that adjusting the molar ratio to 55:40:5 resulted in a maximum EE of 88.38%.

These findings underscore the high performance of ensemble learning in accurately predicting and optimizing the EE of the curcumin-loaded liposomes. The application of this technique provides valuable insights and holds promise for the development of efficient drug delivery systems.