The interaction of native calf thymus DNA with clodinafop-propargyl (CP), in 10 mM HEPES aqueous solutions at neutral pH 7.2, has been investigated by spectrophotometric, circular dichroism (CD), spectrofluorometric, melting temperature (Tm), and viscosimetric techniques. It was found that CP molecules could intercalate between base pairs of DNA as evidenced by hyperchromism in UV absorption band of DNA, an increase in melting temperature, a sharp increase in specific viscosity of DNA, induced CD spectral changes, and increase in the fluorescence of methylene blue (MB)–DNA solutions in the presence of increasing amounts of CP, which indicates that it is able to release the intercalated MB completely. All results suggest that the CP interacts with calf thymus DNA by an intercalative mode of binding.

Transdermal drug delivery (TDD) is an alternative method of drug administration for drugs whose delivery by conventional oral, topical, intravenous and intramuscular methods is of limited efficacy. Recent advances in TDD involve the use of nanoparticles (NPs), which exhibit a great potential to enhance drug permeation across the skin. NPs can also provide controlled release, the ability to deliver both hydrophilic and hydrophobic drugs and reduce side effects, and when used in a TDD method they are also non-invasive. Another developing technology for TDD employs skin patches containing microneedles. Microneedles represent a painless and minimally invasive method of TDD in which micron-sized pores are created in the epidermis to allow delivery of drugs to the blood vessels present in the dermal layer of the skin. New researches have focussed on combining different TDD approaches to overcome previous constraints of drug delivery via conventional methods.

Chemotherapy using cytotoxic agents, such as letrozole (LTZ), is one of the most effective treatments for hormone-dependent breast cancer. Nevertheless, nonspecific targeting of the drug constructs several remarkable systemic toxicities. In this study, we synthesized solid lipid nanoparticles (SLNs) by solvent emulsification evaporation method as LTZ carriers. Nanoparticles were also modified with a cancer cell-targeting ligand, folic acid (FA), and then characterized. Cell membrane damage and cell viability were investigated by lactate dehydrogenase (LDH) and 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays, respectively. Caspase-3 activity and TUNEL assays were performed to verify induced apoptosis. Scanning electron microscopy (SEM) exhibited uniform and spherical morphology of the SLNs-LTZ and FA-SLNs-LTZ. The X-ray diffraction (XRD) confirmed LTZ was dispersed as amorphous in the SLNs. The cell culture results revealed that FA-SLNs-LTZ was significantly more cytotoxic than SLNs-LTZ and free drug against MCF-7 cancer cells in vitro, with a 50% inhibitory concentration (IC50) value of 81 ± 0.89 nM, but both nanoformulations had negligible cytotoxicity toward MCF-10A normal cells and they showed promising biocompatibility. Taken together, these findings indicated the evidence of apoptosis as a mechanism of cell death. This study suggests the potential of FA-SLNs-LTZ for inducing apoptosis in a target-specific manner with minimal systemic side effects.