Polymeric Nanoparticle Delivery of Combination Therapy with Synergistic Effects in Ovarian Cancer

Abstract

Treatment of ovarian cancer is challenging due to late stage diagnosis, acquired drug resistance mechanisms, and systemic toxicity of chemotherapeutic agents. Combination chemotherapy has the potential to enhance treatment efficacy by activation of multiple downstream pathways to overcome drug resistance and reducing required dosages. Sequence of delivery and the dosing schedule can further enhance treatment efficacy. Formulation of drug combinations into nanoparticles can further enhance treatment efficacy. Due to their versatility, polymer-based nanoparticles are an especially promising tool for clinical translation of combination therapies with tunable dosing schedules. We review polymer nanoparticle (e.g., micelles, dendrimers, and lipid nanoparticles) carriers of drug combinations formulated to treat ovarian cancer. In particular, the focus on this review is combinations of platinum and taxane agents (commonly used first line treatments for ovarian cancer) combined with other small molecule therapeutic agents. In vitro and in vivo drug potency are discussed with a focus on quantifiable synergistic effects. The effect of drug sequence and dosing schedule is examined. Computational approaches as a tool to predict synergistic drug combinations and dosing schedules as a tool for future nanoparticle design are also briefly discussed.

Recent Advances in Ovarian Cancer: Therapeutic Strategies, Potential Biomarkers, and Technological Improvements

“…Various improvements and adjustments have been made to the material, and nanoparticle synthesis processes have been continually updated. Recently, there has been growing interest in employing naturally existing protein cages, such as viral particles, as drug carriers [ 127 , 128 , 129 ], while the majority of research has focused on designing nanoparticles for delivering chemotherapeutic agents such as cisplatin, doxorubicin, and paclitaxel as an advanced therapeutic option for OC [ 130 ]. The polymers most widely used in drug delivery systems include polylactic acid (PLA), polylactic-co-glycolic acid (PLGA), poly(γ-glutamylglutamine), polyethylene oxide, modified poly -ε-caprolactone (PCL), and polypropylenimine (PPI) [ 130 , 131 , 132 ].…”

“…Recently, there has been growing interest in employing naturally existing protein cages, such as viral particles, as drug carriers [ 127 , 128 , 129 ], while the majority of research has focused on designing nanoparticles for delivering chemotherapeutic agents such as cisplatin, doxorubicin, and paclitaxel as an advanced therapeutic option for OC [ 130 ]. The polymers most widely used in drug delivery systems include polylactic acid (PLA), polylactic-co-glycolic acid (PLGA), poly(γ-glutamylglutamine), polyethylene oxide, modified poly -ε-caprolactone (PCL), and polypropylenimine (PPI) [ 130 , 131 , 132 ]. In addition to designing diverse nanoparticle materials, it is possible to make various surface modifications to either sustain the controlled release of drugs or enhance drug stability [ 133 ].…”

Recent Advances in Nanoparticle-Based Co-Delivery Systems for Cancer Therapy

“…Patel et al used a thin film hydration approach to create furtive liposomes encapsulated with the P-gp inhibitor tariquidar and the paclitaxel (PTX) [ 13 , 32 ]. An experiment was performed on SKOV-3TR cells, cellosaurus cell line, where the concurrent administration of tariquidar and PTX through prolonged circulating liposomes caused more cytotoxicity in the cancerous cells than administering paclitaxel only, indicating a considerable reversal of the MDR about PTX [ 13 , 68 , 69 ]. Even though various liposome nano-systems have been presented, liposomes’ limited drug loading capacity and poor stability make them unsuitable for large-scale use [ 23 , 25 , 66 , 69 ].…”

Nano-Based Drug Delivery and Targeting to Overcome Drug Resistance of Ovarian Cancers

“…For instance, a combination of PTX and carboplatin polymeric nanoparticles was compared to the free drugs in targeting SKOV-3 and HO-8910 cells. Encapsulation of the drugs into nanoparticles increased their potency for OvCa cells [ 143 ]. Treatment with folic acid-PEGylated calix [ 4 ] arene nanoparticles reduced the tumor volumes of SKOV-3 xenografts compared with the free drugs.…”