Stability testing of tacrolimus-loaded poly(ԑ-caprolactone) nanoparticles by physicochemical assays and Raman spectroscopy

Tacrolimus (TAC) or FK506 is a macrolide lactone isolated from the bacterial fermentation of Streptomyces tsukubaensis which belongs to the group of calcineurin inhibitors. Its main mechanism of action is to act on the immune system. In addition, this drug has been widely explored for skin disorders. However, TAC shows high molecular weight, high hydrophobicity, and low water solubility that can limit its ability to effectively permeate through the skin. Hence, it becomes imperative to develop a percutaneous drug delivery system for increasing its permeation in relation to the conventional ointment and for reducing the dose and the adverse effects as erythema, itching, and burning. Therefore, the aim of this work was to investigate the stability of colloidal suspensions of TAC-loaded poly(ԑ-caprolactone) (PCL) nanoparticles that were stored at room temperature for 120 days. In that sense, pH, particle size, polydispersity index (PDI), zeta potential, and Raman spectroscopy were performed. Significant decrease of pH (p < 0.05) occurred after 60 days for TAC-loaded nanoparticles prepared at high drug concentration (NC-3, 3 mg.mL–1). Loaded formulation showed significant pH changes (p < 0.05 to p < 0.001) after 90 of experiment. Non-loaded nanoparticles revealed significant pH increase (p < 0.05) after 120 days. Particle size and PDI had no statistical difference (p> 0.05) during the time interval investigated. Zeta potential presented statistically significant difference (p < 0.05) only for TAC-loaded nanoparticles after 120 days. The results obtained from Raman spectroscopy showed the suitability of the technique on the evaluation of stability TAC-loaded PCL nanoparticles. The analysis of Raman results demonstrated that the degradation mechanism occurred mainly in amorphous domains of PCL and resulted in an increased polymer crystallinity. Taking all these into account, TAC-loaded nanoparticles had a suitable stability within 60 days of preparation and can be accordingly used for skin disorders during this time interval.