Evaluation of the In Vitro Cytotoxic Activity of Caffeic Acid Derivatives and Liposomal Formulation against Pancreatic Cancer Cell Lines

Abstract

Pancreatic cancer belongs to the most aggressive group of cancers, with very poor prognosis. Therefore, there is an important need to find more potent drugs that could deliver an improved therapeutic approach. In the current study we searched for selective and effective caffeic acid derivatives. For this purpose, we analyzed twelve compounds and evaluated their in vitro cytotoxic activity against two human pancreatic cancer cell lines, along with a control, normal fibroblast cell line, by the classic MTT assay. Six out of twelve tested caffeic acid derivatives showed a desirable effect. To improve the therapeutic efficacy of such active compounds, we developed a formulation where caffeic acid derivative (7) was encapsulated into liposomes composed of soybean phosphatidylcholine and DSPE-PEG2000. Subsequently, we analyzed the properties of this formulation in terms of basic physical parameters (such as size, zeta potential, stability at 4 °C and morphology), hemolytic and cytotoxic activity and cellular uptake. Overall, the liposomal formulation was found to be stable, non-hemolytic and had activity against pancreatic cancer cells (IC50 19.44 µM and 24.3 µM, towards AsPC1 and BxPC3 cells, respectively) with less toxicity against normal fibroblasts. This could represent a promising alternative to currently available treatment options.

The Development of the Innovative Synthesis Methodology of Albumin Nanoparticles Supported by Their Physicochemical, Cytotoxic and Hemolytic Evaluation

“…Thus, in order to gain further overview of possible cytotoxic effects of synthesized nanoparticles, an activity screen in normal human dermal fibroblasts representing healthy cells was performed. Fibroblasts cells are often selected as exemplary control lines to demonstrate safety for various types of formulations [ 50 , 51 , 52 ]. The impact of albumin particles (concentrations of 25, 50 and 100 µL/mL) on the viability of NHDF cells was measured with the MTT assay after incubation for 48 h. Results of the performed investigations are shown in Figure 10 .…”

The influence of the pH on the incorporation of caffeic acid into biomimetic membranes and cancer cells

“…Zaremba-Czogalla et al . 52 encapsulated caffeic acid derivative into liposomes composed of soybean phosphatidylcholine and DSPE-PEG2000 obtaining 93% of the entrapment efficiency. The loaded liposomes had larger size compared to unloaded ones.…”

“…These liposomes were able to achieve a cumulative release of 71% of entrapped CA within 7 h in PBS solution (pH 7.4), whereas 95% of free caffeic acid diffused within 4 h. Morphological analysis of these liposomes by SEM showed spherical shaped 3D globular vesicles. Zaremba-Czogalla et al 52 encapsulated caffeic acid derivative into liposomes composed of soybean phosphatidylcholine and DSPE-PEG2000 obtaining 93% of the entrapment efficiency. The loaded liposomes had larger size compared to unloaded ones.…”

Design and Development of a New Type of Hybrid PLGA/Lipid Nanoparticle as an Ursolic Acid Delivery System against Pancreatic Ductal Adenocarcinoma Cells

“…The addition of a lipid coat in the second generation of UA-loaded particles resulted in increased values of encapsulation efficiency, from 53% to 69.6%. This increase could be correlated with the entrapment of some of the fraction of the UA between the acyl chains of the lipid layer coating the particles; a similar phenomenon is known from the encapsulation of compounds in a liposomal bilayer [ 68 , 69 ]. A very important aspect of this assay is the phenomenon where, no matter what UA-to-polymer weight ratio is used, the value of the encapsulation efficiency is the same; the diagram is somewhat flat in this matter.…”

“…In our studies, we have incubated our UA-loaded hybrid nanoparticles with 50% FBS solution for 72 h hours. The initial loss of payload, immediately after the injection of the hybrid particle suspension into the heated solution of FBS, suggests that some of the UA could be encapsulated between the acyl chains of the phospholipid coat, similar to passive-loading drug encapsulation in liposomes [ 68 , 69 ]. This could also suggest increased values of UA encapsulation efficiency into hybrid lipid–polymeric nanoparticles compared to bare particles from our previous work [ 43 ].…”