A comparative investigation of release kinetics of paclitaxel from natural protein and macromolecular nanocarriers in nanoscale drug delivery systems

Understanding the release behaviour of nanodrugs is a crucial step to better assess and control therapeutic outcomes and unfavourable side effects. Herein, we report a systematic study comparing the release kinetics and thermodynamics of paclitaxel (PTX) from supramolecularly assembled sub-micron particles based on natural macromolecules such as zein, whey, casein, bovine serum albumin (BSA) and conventional stabilizers such as pluronic F-127 (poloxamer 407), and β-cyclodextrin (β-CD) to gain insights into the role of carrier chemistry. For this purpose, nanomedicines with statistically indifferent sizes —in the range of 191.0 ± 0.8 nm (BSA) to 243.3 ± 11.6 nm (zein) were prepared (p > 0.05). The zeta potential values ranged from −3.2 ± 1.1 mV (pluronic F-127) to −17.2 ± 1.8 mV (whey) in phosphate buffered saline. The type of nanocarrier significantly influenced the long-term steady-state plateau of the release, resulting in a cumulative release of 70.3 ± 2.0 % of PTX from casein (the highest) and 46.8 ± 4.7 % of PTX from zein (the lowest). Time-resolved release data were analysed with various kinetical models, encompassing zero-order, first-order, Higuchi, Peppas-Sahlin, and Korsmeyer-Peppas kinetics. The analysis revealed that the Korsmeyer-Peppas model best captured the data. For these nanomedicines, the half-life of the encapsulated drugs was found to be 106.4 ± 31.3 h (zein), 4.7 ± 1.2 h (whey), 10.7 ± 1.8 h (pluronic F-127), 6.4 ± 0.9 h (casein), 10.8 ± 3.2 h (β-CD), and 4.0 ± 1.0 h (BSA). TEM characterization revealed differences in the macromolecular arrangement of the active ingredient within these nanocarriers, in addition to the structural differences among the various encapsulating agents. These differences manifested as variations in the internal nanostructures, leading to the creation of distinct microenvironments that could either facilitate or impede the movement of PTX molecules through the encapsulant matrices. In clinical settings, such fine details of nanocarrier design are important: by choosing the most appropriate nanocarrier (or their mixtures), clinicians can fine-tune drug administration to obtain the intended therapeutic window while mitigating the risk of potential negative reactions.