Abstract
Nanosized multi-drug delivery systems provide synergistic effects between drugs and bioactive compounds, resulting in increased overall efficiency and restricted side effects compared to conventional single-drug chemotherapy. In this study, we develop an amphiphilic heparin-poloxamer P403 (HP403) nanogel that could effectively co-load curcuminoid (Cur) and cisplatin hydrate (CisOH) (HP403@CisOH@Cur) via two loading mechanisms. The HP403 nanogels and HP403@CisOH@Cur nanogels were closely analyzed with 1H-NMR spectroscopy, FT-IR spectroscopy, TEM, and DLS, exhibiting high stability in spherical forms. In drug release profiles, accelerated behavior of Cur and CisOH at pH 5.5 compared with neutral pH was observed, suggesting effective delivery of the compounds in tumor sites. In vitro studies showed high antitumor activity of HP403@CisOH@Cur nanogels, while in vivo assays showed that the dual-drug platform prolonged the survival time of mice and prevented tail necrosis. In summary, HP403@CisOH@Cur offers an intriguing strategy to achieve the cisplatin and curcumin synergistic effect in a well-designed delivery platform that increases antitumor effectiveness and overcomes undesired consequences caused by cisplatin in breast cancer treatment.
Highlights
Cisplatin (Cis-diamminedichloroplatinum (II)) is a standard first-line treatment for human breast cancer [1,2,3,4,5,6]
The activation of the nitrophenyl chloroformate (NPC) molecule and P403 was confirmed with a new signal at 4.45 ppm (f) [44,45]
The chemical shift from 4.45 ppm (f) to 4.22 ppm (k) occurs due to the NPC substitution by 3-amino-1-propanol, which indicates the successful synthesis of NPC-P403-OH
Summary
Cisplatin (Cis-diamminedichloroplatinum (II)) is a standard first-line treatment for human breast cancer [1,2,3,4,5,6] It is one of the prime anticancer drugs for many types of solid tumors and the first platinum compound approved by the FDA for treating testicular and ovarian cancer since 1978 [3,4,5,6]. The hydrophobic cores containing water-insoluble drugs are surrounded by the hydrophilic shell, increasing the solubility and permeability of loaded compounds [32] Within this category, poloxamer P403 is a prospective material due to its high ratio of PPO (as compared to poloxamer P407, pluronic F127), low critical micelle concentration (CMC) value, and considerable internal space [33]. The result could partially clarify the synergistic effect of aquated cisplatin and Cur in a well-designed delivery platform in antitumor activity
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