Potential of injectable psoralen polymeric lipid nanoparticles for cancer therapeutics

Abstract

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer (BC) with a poor prognosis. Currently, chemotherapy and neoadjuvant chemotherapy continue to have limited efficacy in TNBC. With the deepening of research, nano targeted therapy shows a good application prospect in TNBC. Psoralen (PSO), an active component of Psoralea corylifolia, has significant advantages in inhibiting the growth of TNBC, but its poor solubility hampers its clinical practice. In this study, injectable psoralen polymer lipid nanoparticles (PSO-PLNs) were developed to deliver the hydrophobic drug to the target site and improve bioavailability. These nanoparticles were fully characterized in terms of morphology, particle size, surface zeta potential, encapsulation efficiency, drug loading, stability, and in vitro release profile. Besides, structural characteristics were determined by ultraviolet (UV) and infrared spectroscopy. Finally, in vivo pharmacokinetic studies of PSO-PLNs were performed in rats. The characteristic absorption of PSO and PSO-PLNs appeared in UV, indicating that PSO-PLNs had encapsulated PSO; there was no obvious characteristic absorption of PSO in infrared spectra, indicating that PSO was mostly encapsulated in the nano-shell. PSO-PLNs could maintain stable physicochemical properties for 1.5 months when stored at 4 °C. PSO-PLNs selectively released PSO at pH 6.5, and the sustained and controlled release effect was significantly different from that of PSO (p < 0.01). Pharmacokinetic studies in vivo demonstrated that PSO-PLNs could improve PSO bioavailability by increasing blood drug concentration and plasma protein binding rate. In summary, injectable PSO-PLNs could be considered as promising delivery system for advanced cancer therapeutics.

Keywords

• Polymer lipid nanoparticles
• Psoralen
• Pharmacokinetics
• Plasma protein binding rate
• Cancer