PLGA Nanoparticles for the Intraperitoneal Administration of CBD in the Treatment of Ovarian Cancer: In Vitro and In Ovo Assessment

Abstract

The intraperitoneal administration of chemotherapeutics has emerged as a potential route in ovarian cancer treatment. Nanoparticles as carriers for these agents could be interesting by increasing the retention of chemotherapeutics within the peritoneal cavity. Moreover, nanoparticles could be internalised by cancer cells and let the drug release near the biological target, which could increase the anticancer efficacy. Cannabidiol (CBD), the main nonpsychotropic cannabinoid, appears as a potential anticancer drug. The aim of this work was to develop polymer nanoparticles as CBD carriers capable of being internalised by ovarian cancer cells. The drug-loaded nanoparticles (CBD-NPs) exhibited a spherical shape, a particle size around 240 nm and a negative zeta potential (−16.6 ± 1.2 mV). The encapsulation efficiency was high, with values above 95%. A controlled CBD release for 96 h was achieved. Nanoparticle internalisation in SKOV-3 epithelial ovarian cancer cells mainly occurred between 2 and 4 h of incubation. CBD antiproliferative activity in ovarian cancer cells was preserved after encapsulation. In fact, CBD-NPs showed a lower IC50 values than CBD in solution. Both CBD in solution and CBD-NPs induced the expression of PARP, indicating the onset of apoptosis. In SKOV-3-derived tumours formed in the chick embryo model, a slightly higher—although not statistically significant—tumour growth inhibition was observed with CBD-NPs compared to CBD in solution. To sum up, poly-lactic-co-glycolic acid (PLGA) nanoparticles could be a good strategy to deliver CBD intraperitoneally for ovarian cancer treatment.

Repurposing Cannabidiol as a Potential Drug Candidate for Anti-Tumor Therapies

“…Due to these limitations, nanoparticles loaded with CBD (CBD-NPs) at a ratio of 1:5 or 3% ( w / w ) have first been tested to treat ovarian cancer cells in vitro and for in vivo models. Compared to free CBD in organic solvents, CBD-NPs induce apoptosis and tumor growth inhibition at lower IC50 values [ 102 ]. CBD in lipid nanocarriers exhibits a high brain targeting ability by enhancing the passage across the blood-brain barrier in vitro and in ovo and, therefore, might provide a novel strategy to treat CNS tumors [ 103 ].…”

Challenges of Cannabinoid Delivery: How Can Nanomedicine Help?

“…Cannabinoid nanodelivery systems have been applied in vitro and in vivo to serve as therapeutic strategies. A number of studies are building nanoparticles for nanodelivery of cannabis, cannabinoids and ECS components as nanotherapeutics [6,[16][17][18][19][20][21][22][23][24][25][26]. They include strategies for creating cannabinoid delivery systems incorporating cannabinoid nanoconjugates in a multifunctional nanocarrier.…”

(Endo)Cannabinoids and Gynaecological Cancers

“…Some preliminary evidence suggests that OEA and its structural analogues may also have a beneficial effect on inhibiting ovarian cancer growth, but these data need to be confirmed in vivo [ 60 ]. There is little evidence that plant-derived (phyto)cannabinoids have any effect on ovarian biology or ovarian cancer development or progression, a concept that came from a study where SKOV-3-derived tumours were grown on the chorioallantoic membrane of fertilised chicken eggs [ 145 ], and then were treated with CBD-containing nanoparticles. The data indicated that CBD caused a 1.35- to 1.50-fold reduction in tumour size depending on the type of CBD formulation used [ 145 ].…”

“…There is little evidence that plant-derived (phyto)cannabinoids have any effect on ovarian biology or ovarian cancer development or progression, a concept that came from a study where SKOV-3-derived tumours were grown on the chorioallantoic membrane of fertilised chicken eggs [ 145 ], and then were treated with CBD-containing nanoparticles. The data indicated that CBD caused a 1.35- to 1.50-fold reduction in tumour size depending on the type of CBD formulation used [ 145 ]. The authors indicated that these nanoparticle preparations might be useful in the treatment of peritoneal metastases of ovarian cancer, possibly with lower adverse drug effects [ 145 ].…”

“…The data indicated that CBD caused a 1.35- to 1.50-fold reduction in tumour size depending on the type of CBD formulation used [ 145 ]. The authors indicated that these nanoparticle preparations might be useful in the treatment of peritoneal metastases of ovarian cancer, possibly with lower adverse drug effects [ 145 ]. Furthermore, the preparations also reduced SKOV-3 ovarian cancer cell numbers in vitro, to almost zero within 48 h, possibly making this a good candidate for a randomised clinical trial.…”