Suitability of GnRH Receptors for Targeted Photodynamic Therapy in Head and Neck Cancers

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Novel Crizotinib–GnRH conjugates revealed the significance of lysosomal trapping in GnRH-based drug delivery systems

Several promising anti-cancer drug–GnRH (gonadotropin-releasing hormone) conjugates have been developed in the last two decades, although none of them have been approved for clinical use yet. Crizotinib is an effective multi-target kinase inhibitor, approved against anaplastic lymphoma kinase (ALK)- or ROS proto-oncogene 1 (ROS-1)-positive non-small cell lung carcinoma (NSCLC); however, its application is accompanied by serious side effects. In order to deliver crizotinib selectively into the tumor cells, we synthesized novel crizotinib analogues and conjugated them to a [d-Lys6]–GnRH-I targeting peptide. Our most prominent crizotinib–GnRH conjugates, the amide-bond-containing [d-Lys6(crizotinib*)]–GnRH-I and the ester-bond-containing [d-Lys6(MJ55*)]–GnRH-I, were able to bind to GnRH-receptor (GnRHR) and exert a potent c-Met kinase inhibitory effect. The efficacy of compounds was tested on the MET-amplified and GnRHR-expressing EBC-1 NSCLC cells. In vitro pharmacological profiling led to the conclusion that that crizotinib–GnRH conjugates are transported directly into lysosomes, where the membrane permeability of crizotinib is diminished. As a consequence of GnRHR-mediated endocytosis, GnRH-conjugated crizotinib bypasses its molecular targets—the ATP-binding site of RTKs— and is sequestered in the lysosomes. These results explained the lower efficacy of crizotinib–GnRH conjugates in EBC-1 cells, and led to the conclusion that drug escape from the lysosomes is a major challenge in the development of clinically relevant anti-cancer drug–GnRH conjugates

Study on Adsorption of Essential Oils on Polylactic Acid Microparticles

Polylactic acid (PLA) is a biodegradable polymer that is widely used in medical devices, drug delivery systems, fibers for packaging containers and textiles. However, given that interactions between the polymer and the materials in contact with it affect its applications, it is important to study its adsorption and diffusion properties. The adsorption capacity of different polylactic acid particles regarding different additives, e.g. essential oils (Thymus vulgaris, Melissa officinalis and Foeniculum vulgare), was investigated. PLA microparticles of various sizes were prepared by a solvent emulsification evaporation method. In this study, the specific adsorption of essential oils on PLA microparticles was also investigated, which is related to the solubility parameters of essential oils. The experiments were performed using three different solutions of essential oils and ethanol as a solvent. Two sets of PLA microparticles were prepared with different solvents using three different particle sizes. PLA microparticles exhibited different adsorption properties depending on the solvent that was used for their production. Samples of particles prepared using the solvent dichloromethane had a higher essential oil uptake than those prepared with chloroform. The uptake of essential oil solution did not change significantly (∼60%) by varying either the type of solvent used for PLA preparation or PLA particle size. The solubility of the essential oils affects the specific adsorption of essential oils on the microparticles. Among the components of the Hansen solubility parameters (HSPs), the polarity of essential oils is strongly related to adsorption

Method for the Determination of Solvent Sorption of Polylactic Acid and the Effect of Essential Oils on the Sorption Properties

The investigation of the adsorption and diffusion properties of polylactic acid (PLA) is very important, because during the application of the polymer, interactions can occur between the polymer and its environment that can affect its properties and application. The aim of our work was to investigate a method for determining the solvent sorption capacity of PLA and to investigate how different additives, such as essential oils, affect the solvent sorption properties of the polymer. Experiments were carried out to explore the correlation between the solvent uptake of two different types of PLA granules and the solubility parameter of the selected 5 essential oils (Melissa officinalis, Mentha piperita, Foeniculum vulgare, Majorana hortensi, Thymus vulgaris) for 3 solvents. It was observed, that application of essential oils was changed the solvent uptake of the granules differently. While one granule solvent uptake decreased on average by 2–3 wt.%, the other increased by a similar amount. The difference of sorption capacity of pure and essential oil containing solvent were between 20–190%. The specific essential oil uptake was highest in solutions with a concentration of 2.00 mg/mL, about 2.00 mg EO/g PLA. In alcoholic solutions we observed a relation between the solvent uptake of PLA and the solubility parameter of the relevant essential oil

Adsorption Properties of Essential Oils on Polylactic Acid Microparticles of Different Sizes

The interaction between the polymer and the materials in contact with it affects its applicability. This can be particularly important in applications such as packaging or controlled drug delivery systems. Because of these interactions, the adsorption and diffusion properties of polylactic acid (PLA) are important. The absorption capacity of different polylactic acid particles for different additives like essential oils (Thymus vulgaris, Melissa officinalis, and Foeniculum vulgare essential oils) was investigated depending on the concentration of the essential oil. The PLA microparticles were prepared by the solvent evaporation emulsification method. The prepared particles had a degree of crystallinity of 0.1% and 16.1%, respectively, according to the granules used. This affects the particles’ adsorption properties. The specific essential oil uptake of the more crystalline microparticles was on average 15% higher than that of the amorphous particles. The specific amount of essential oil adsorbed decreases with the decreasing concentration of essential oil in the solutions. We also investigated whether the amount of essential oil taken up was correlated with the solubility parameter of the essential oils. We concluded that the difference between the adsorption of the essential oils on the polymer was related to the essential oils’ Hansen solubility parameter