Abstract
Cervical cancer is usually diagnosed in the later stages despite many campaigns for early detection and continues to be a major public health problem. The standard treatment is cisplatin-based chemotherapy plus radiotherapy, but patient response is far from ideal. In the research for new drugs that enhance the activity of cisplatin, different therapeutic agents have been tested, among them the antiprogestin mifepristone. Nevertheless, the efficacy of cisplatin is limited by its low specificity for tumor tissue, which causes severe side effects. Additionally, cervical tumors often become drug resistant. These problems could possibly be addressed by the use of liposome nanoparticles to encapsulate drugs and deliver them to the target. The aim of this study was to prepare liposome nanoparticles that co-encapsulate cisplatin and mifepristone, evaluate their cytotoxicity against HeLa cells and in vivo with subcutaneous inoculations of xenografts in nu/nu mice, and examine some plausible mechanisms of action. The liposomes were elaborated by the reverse-phase method and characterized by physicochemical tests. The nanoparticles had a mean particle size of 109 ± 5.4 nm and a Zeta potential of −38.7 ± 1.2 mV, the latter parameter indicating a stable formulation. These drug-loaded liposomes significantly decreased cell viability in vitro and tumor size in vivo, without generating systemic toxicity in the animals. There was evidence of cell cycle arrest and increased apoptosis. The promising results with the co-encapsulation of cisplatin/mifepristone warrant further research.
Highlights
Cervical cancer is the fourth most common malignant neoplasm and the fourth leading cause of cancer death in women worldwide [1], being especially problematic in developing countries such as Mexico [2]
There are data that show that lipoplatin does not cause damage to the proximal kidney tubules as does cisplatin for several reasons: cisplatin remains protected by the lipid capsule, and the entrance of lipoplatin particles into the kidney tubule cells is limited; lipoplatin is released through the kidney with a half-life of 60–117 h compared to 6.5 h for conventional cisplatin, these pharmacokinetic differences could explain the low renal toxicity [31]
A liposomal nanosystem was developed to co-encapsulate cisplatin and mifepristone—two drugs that have demonstrated a synergistic effect on several types of cancer cells
Summary
Cervical cancer is the fourth most common malignant neoplasm and the fourth leading cause of cancer death in women worldwide [1], being especially problematic in developing countries such as Mexico [2]. Since it is initially a slow-growing cancer, there are many campaigns for early detection and tests are widely available. It is often detected in the later stages when rapid proliferation is underway. The prognosis for patients in stages III and IV is still unfavorable [5,6]
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