Development of Parvifloron D-loaded Smart Nanoparticles to Target Pancreatic Cancer

Abstract

Pancreatic cancer is the eighth leading cause of cancer death worldwide. For this reason, the development of more effective therapies is a major concern for the scientific community. Accordingly, plants belonging to Plectranthus genus and their isolated compounds, such as Parvifloron D, were found to have cytotoxic and antiproliferative activities. However, Parvifloron D is a very low water-soluble compound. Thus, nanotechnology can be a promising delivery system to enhance drug solubility and targeted delivery. The extraction of Parvifloron D from P. ecklonii was optimized through an acetone ultrasound-assisted method and isolated by Flash-Dry Column Chromatography. Then, its antiproliferative effect was selectivity evaluated against different cell lines (IC50 of 0.15 ± 0.05 μM, 11.9 ± 0.7 μM, 21.6 ± 0.5, 34.3 ± 4.1 μM, 35.1 ± 2.2 μM and 32.1 ± 4.3 μM for BxPC3, PANC-1, Ins1-E, MCF-7, HaCat and Caco-2, respectively). To obtain an optimized stable Parvifloron D pharmaceutical dosage form, albumin nanoparticles were produced through a desolvation method (yield of encapsulation of 91.2%) and characterized in terms of size (165 nm; PI 0.11), zeta potential (−7.88 mV) and morphology. In conclusion, Parvifloron D can be efficiently obtained from P. ecklonii and it has shown selective cytotoxicity to pancreatic cell lines. Parvifloron D nanoencapsulation can be considered as a possible efficient alternative approach in the treatment of pancreatic cancer.

Anti-Migratory and Pro-Apoptotic Properties of Parvifloron D on Triple-Negative Breast Cancer Cells

“…In another study, Silva et al reported the cytotoxic effect of ParvD in melanoma cell lines B16V5 and A375 with IC 50 values of 6.86 µM and 6.24 µM, following a 24 h period [12]. In comparison with the only reported study so far using the non-metastatic breast cancer cell line MCF7 [13] (IC 50 value of 35.10 µM), our results demonstrate that ParvD is highly cytotoxic for MDA-MB-231 cells, with an IC 50 value of 2.48 µM. This is an encouraging finding, since MDA-MB-231 cells exhibit a high level of resistance to an array of chemotherapeutic drugs [31].…”

“…Therefore, future studies should be taken to develop adequate delivery systems that allow the targeting of this compound specifically to breast cancer cells. Such approaches were proposed by Silva et al (2016) and Santos-Rebelo et al (2018) using hybrid nanoparticles to target ParvD to melanoma and pancreatic cancer cells [12,13].…”

Insight the Biological Activities of Selected Abietane Diterpenes Isolated from Plectranthus spp.

“…They propose that the mechanism of action is associated with a decrease in mitochondrial membrane potential and the release of cytochrome c, and that it may be amplified by inhibition of extracellular signal-regulated kinases (ERKs) 1/2 signaling; they also suggest it may be caused by a mechanism dependent on intracellular ROS generation in leukemia cells [19]. Santos-Rebelo et al also report that Parv D obtained from P. ecklonii displayed a cytotoxic effect on pancreatic cell lines [42]. In the present study, it was found that of the four tested compounds, Parv D treatment induced the highest level of phosphorylated histone.…”

A Perspective on therapeutic potential of weeds

“…Osmunda regalis (Royal fern) [82]. Parvi loron D isolated from Plectranthus ecklonii via lash dry column chromatography exhibited antiproliferative effects against pancreatic cancer when evaluated against HaCat, BxPC3, Caco-2, MCF-7, Ins1-E and PANC-1 cell lines [53]. Aqueous extract of weed Solanum nigrum at concentration of 10 g/l caused 43% cytotoxicity in MCF7 cell line by inhibiting migration, suppression of hexokinase and pyruvate kinase [86].…”