Antineoplastic effect of paclitaxel-loaded polymeric nanocapsules on malignant human ovarian carcinoma cells (SKOV-3)

Abstract

Drug resistance is the main responsible for chemotherapy failure in ovarian cancer treatment. In this study, we looked at increasing the anticancer effect of paclitaxel (PTX) through its encapsulation in novel polymeric nanocapsules to develop a novel, less invasive PTX-loaded nano-delivery system. These were synthesized by a microemulsion-based methodology, and their particle size and shapes determined using dynamic light scattering (DLS) and field emission scanning electron microscopy (FESEM). The synthesized PTX-loaded polymeric nanocapsules showed spherical morphology with approximately ca. 18 nm. In vitro cytotoxicity analysis of free administered PTX, bare and PTX-loaded polymeric nanocpasules by means of the MTT assay showed that much lower concentration of PTX loaded inside polymeric nanocapsules (2.2 µg/ml) were needed to achieve a similar therapeutic activity than the free administered drug (14.4 µg/ml). Polymer nanocapsule encapsulation of PTX then improved the therapeutic efficacy as shown by the reduction of IC50 concentration. MYC, MECOM, PRKCl gene and caspases-3, −8, and −9 protein expressions involved in the apoptotic pathway after the treatment of SKOV-3 cells with PTX-loaded polymeric nanocapsules were assessed by qRT-PCR and fluorometric assay, respectively. The expression level of MECOM increased 1.67 times upon administration of PTX-loaded polymeric nanocapsules compared with untreated SKOV-3 cancer cells as the control group (P < 0.001); conversely, MYC and PRKCl gene expressions were 0.40 and 0.45 times lower compared to control cancerous cells (p < 0.001). The expression of caspase-3, caspase-8, and caspase-9 proteins also significantly increased after the administration of PTX-loaded polymeric nanocapsules to cancer cells (p ≤ 0.001). On the other hand, fluorescence microscopy analysis showed nuclei fragmentation after administration of 24.1 μg/mL of PTX-loaded polymeric nanocapsules, which is accompanied by morphological cell alterations, confirming the cytostatic activity of the nanoformulation. Therefore, the synthesized PTX-loaded polymer nanocapsules could be promise and potential nano-delivery system for PTX delivery in ovarian cancer chemotherapy