Paclitaxel-Loaded Self-Assembled Lipid Nanoparticles as Targeted Drug Delivery Systems for the Treatment of Aggressive Ovarian Cancer

Abstract

Chemotherapy using cytotoxic agents, such as paclitaxel (PTX), is one of the most effective treatments for advanced ovarian cancer. However, due to nonspecific targeting of the drug and the presence of toxic solvents required for dissolving PTX prior to injection, there are several serious side effects associated with this treatment. In this study, we explored self-assembled lipid-based nanoparticles as PTX carriers, which were able to improve its antitumour efficacy against ovarian cancer. The nanoparticles were also functionalized with epidermal growth factor receptor (EGFR) antibody fragments to explore the benefit of tumor active targeting. The formulated bicontinuous cubic- and sponge-phase nanoparticles, which were stabilized by Pluronic F127 and a lipid poly(ethylene glycol) stabilizer, showed a high capacity of PTX loading. These PTX-loaded nanoparticles also showed significantly higher cytotoxicity than a free drug formulation against HEY ovarian cancer cell lines in vitro. More importantly, the nanoparticle-based PTX treatments, with or without EGFR targeting, reduced the tumor burden by 50% compared to PTX or nondrug control in an ovarian cancer mouse xenograft model. In addition, the PTX-loaded nanoparticles were able to extend the survival of the treatment groups by up to 10 days compared to groups receiving free PTX or nondrug control. This proof-of-concept study has demonstrated the potential of these self-assembled lipid nanomaterials as effective drug delivery nanocarriers for poorly soluble chemotherapeutics, such as PTX.

Ovarian Cancer, Cancer Stem Cells and Current Treatment Strategies: A Potential Role of Magmas in the Current Treatment Methods

“…Numerous nanoparticle drug formulations are currently in development and evaluation stages in early and late-phase clinical trials [183]. These nanoparticles are loaded with ligands such as antibodies, peptides, aptamers for targeting various plasma membrane associated antigens on tumours, thus allowing formulations to be customized for patients [183,184].…”

“…Although this study provided a novel mechanism for focal adhesion kinase knockdown using a siRNA-formulated nanoparticle-based system to tackle chemoresistance in OC, other signaling pathways involved in chemoresistance mechanisms can be explored. Recently, we have shown that lipid-based cubosome formulated paclitaxel provides superior results in terms of greater reduction in tumour burden and increased progression-free survival in a mouse model of OC [184].…”

Theranostic combinatorial drug-loaded coated cubosomes for enhanced targeting and efficacy against cancer cells

“…It has been reported that there exists an extremely high mortality rate in malignancies occurring in the genital tract of the female which includes cervical, ovarian, and endometrial cancers. This may result due to recurrence of cancer after persistence of minute residue of malignancy in the cells 28 . Therefore, in this study, we prepared coated cubosomes decorated with two hydrophobic anticancer drugs cisplatin and paclitaxel to study their efficacy against the HeLa cells, the most documented cell line of cervical cancer.…”

The Response of Second Line Chemotherapy Platinum Resistant Ovarian Cancer in Sudan: 2013-2017

“…But taken in account the population density between two states, the prevalence were higher in Aljazeera state compared to Khartoum state 2:1 respectively (51). The second line platinum resistance chemotherapy include many type such as liposomal pegylated doxorubicin (55), topotecan (56), paclitaxel (57), oral etoposide (58) and gemcitabine (51). All of these chemotherapy agents have similar response treatment rate which is about 10 % (5).…”