Structural Modification of Nanomicelles through Phosphatidylcholine: The Enhanced Drug-Loading Capacity and Anticancer Activity of Celecoxib-Casein Nanoparticles for the Intravenous Delivery of Celecoxib

Abstract

This study aims to stabilize loaded celecoxib (CX) by modifying the structure of casein nanoparticles through phosphatidylcholine. The results show that Egg yolk phosphatidylcholine PC98T (PC) significantly increased the stability of CX-PC-casein nanoparticles (NPs) (192.6 nm) from 5 min (CX-β-casein-NPs) to 2.5 h at 37 °C. In addition, the resuspended freeze-dried NPs (202.4 nm) remained stable for 2.5 h. Scanning electron microscopy indicated that PC may block the micropore structures in nanoparticles by ultrasonic treatment and hence improve the physicochemical stability of CX-PC-casein-NPs. The stability of the NPs was positively correlated with their inhibiting ability for human malignant melanoma A375 cells. The structural modification of CX-PC-casein-NPs resulted in an increased intracellular uptake of CX by 2.4 times than that of the unmodified ones. The pharmacokinetic study showed that the Area Under Curve (AUC) of the CX-PC-casein-NPs was 2.9-fold higher in rats than that of the original casein nanoparticles. When CX-PC-casein-NPs were intravenously administrated to mice implanted with A375 tumors (CX dose = 16 mg/kg bodyweight), the tumor inhibition rate reached 56.2%, which was comparable to that of paclitaxel (57.3%) at a dose of 4 mg/kg bodyweight. Our results confirm that the structural modification of CX-PC-casein-NPs can effectively prolong the remaining time of specific drugs, and may provide a potential strategy for cancer treatment.

Superior anti-infective potential of eugenol–casein nanoparticles combined with polyethylene glycol against Colletotrichum musae infections

“…The amount of EL remaining in the NPs was determined using a previously reported procedure. 31 Briefly, a NP dispersion was centrifuged at 10 000 g to separate the free EL. Then, the clear aqueous phase (50 μL) was added to 450 μL of methanol to denature the protein.…”

Micellar Drug Delivery Systems Based on Natural Biopolymers

“…In another study, the same research team showed that Cx/β-CN micelles are metastable supramolecular assemblies that transform upon heating to thermodynamically stable drug free β-CN micelles while releasing their drug load [149]. More recently, Xv et al [150] showed that egg yolk phosphatidylcholine PC98T (PC) significantly increased the physicochemical stability of Cx/PC-β-CN NPs (192.6 nm) from 5 min (Cx/β-CN micelles) to 2.5 h at 37 • C. The images of these NPs are provided in Figure 15. β-CN micelles were further used in order to orally deliver a synergistic combination of a chemotherapeutic drug (Paclitaxel) (PTX) and a P-glycoprotein-specific transport inhibitor (Tariquidar) (TQD), which were individually encapsulated within these micelles, for overcoming multidrug resistance (MDR) in gastric cancer [152].…”

“…In another study, the same research team showed that Cx/β-CN micelles are metastable supramolecular assemblies that transform upon heating to thermodynamically stable drug free β-CN micelles while releasing their drug load [ 149 ]. More recently, Xv et al [ 150 ] showed that egg yolk phosphatidylcholine PC98T (PC) significantly increased the physicochemical stability of Cx/PC-β-CN NPs (192.6 nm) from 5 min (Cx/β-CN micelles) to 2.5 h at 37 °C. The images of these NPs are provided in Figure 15 .…”

NSAIDs: Old Acquaintance in the Pipeline for Cancer Treatment and Prevention─Structural Modulation, Mechanisms of Action, and Bright Future

“…Interestingly, these nanocarriers demonstrated synergistic effects in cancer therapy and reduced their gastric side effects. Some important formulation approaches with NSAIDs or NSAID derivatives alone and combined with chemotherapeutic agents are micelles, − nanomicelles, − liposomes, , transferrin-bearing vesicles, nanoparticles, ,− PEGylated nanocochleate, nanoexosomes, , cyclodextrins, and poloxamers (Table ).…”