Tripalmitin nanoparticle formulations significantly enhance paclitaxel antitumor activity against breast and lung cancer cells in vitro

Abstract

Paclitaxel (PTX) is one of the drugs of choice in the treatment of breast and lung cancer. However, its severe side effects, including mielosuppression, cardiotoxicity and neurotoxicity, frequently cause treatment to be discontinued. Solid lipid nanoparticles (NPs) of glyceril tripalmitate (tripalmitin) loaded with PTX (Tripalm-NPs-PTX) including modifications by the addition of hexa(ethylene glycol), β-cyclodextrin and macelignan were developed. All NPs-PTX formulations displayed excellent hemocompatibility and significantly enhanced PTX antitumor activity in human breast (MCF7, MDAMB231, SKBR3 and T47D) and lung (A549, NCI-H520 and NCI-H460) cancer cells. Tripalm-NPs-PTX decreased PTX IC50 by as much as 40.5-fold in breast and 38.8-fold in lung cancer cells and Tripalm-NPs-PTX macelignan inhibited P-glycoprotein in resistant tumor cells. In addition, Tripalm-NPs-PTX significantly decreased the volume of breast and lung multicellular tumor spheroids that mimics in vivo tumor mass. Finally, Tripalm-NPs-PTX decreased the PTX IC50 of cancer stem cells (CSCs) derived from both lung and breast cancer cells (6.7- and 14.9-fold for MCF7 and A549 CSCs, respectively). These results offer a new PTX nanoformulation based on the use of tripalmitin which improves the antitumor activity of PTX and that may serve as an alternative PTX delivery system in breast and lung cancer treatment.

7-Epitaxol Induces Apoptosis and Autophagy in Head and Neck Squamous Cell Carcinoma through Inhibition of the ERK Pathway

“…Among various chemotherapeutic agents, paclitaxel is widely used as a cytotoxic and apoptosis-inducing agent in many cancer types, including ovarian, breast, brain, and lung cancers [11][12][13][14]. Paclitaxel, also known as Taxol, is a naturally occurring tricyclic diterpenoid compound found in the evergreen tree, Taxus brevifolia [15].…”

Aptamers: an emerging navigation tool of therapeutic agents for targeted cancer therapy

“…69 In addition to this, owing to its indiscriminative distribution in tumor and normal tissues, PTX frequently causes other serious side effects. 70 Therefore, it is highly desirable to develop PTX derivatives with high water solubility as well as tumortargeting properties.…”

Functionalized Liposome and Albumin-Based Systems as Carriers for Poorly Water-Soluble Anticancer Drugs: An Updated Review

“…The SLNs allow enhanced pharmacokinetic properties and modulate the release of drugs [ 77 , 78 ], protecting them from chemical degradation; they increase permeation through the biological barrier [ 79 , 80 ]; they have the possibility of surface modification [ 81 ] and co-delivery of several therapeutic agents; allow controlled drug delivery; exhibit absence of biotoxicity; promote the bioavailability of poorly water-soluble drugs [ 53 , 82 , 83 ]. Besides, this carrier system can increase the specificity and decrease the cytotoxicity of conventional anticancer therapy, proving that SLNs improve the therapeutic efficacy of anticancer drugs [ 84 , 85 ]. However, SLNs have some limitations, such as reduced loading capacity, stability problems and agglomeration during storage, high operative temperature and low circulation time [ 75 ].…”

“…Furthermore, Leiva et al [ 85 ] developed solid lipid nanoparticles of glyceril tripalmitate, loaded with Paclitaxel (PTX) (Tripalm-NPs-PTX), including modifications by the addition of hexa(ethylene glycol) (OEG), β-cyclodextrin (β-CD) and macelignan (MAC). All the formulations significantly enhanced PTX antitumor activity against human breast and lung cancer cells ( Figure 3 ).…”