This study explores the potential of using liposomal electrokinetic chromatography as a ranking method for the rapid and simultaneous evaluation of drug-membrane interactions of a larger group of substances and assessing their sensitivity to tissue-specific parameters, namely pH, temperature, and lipid composition. We used a group of nine model drug substances to manifest how molecules could be classified for the relative sensitivity of drug-membrane interactions to pH and temperature. We observed that increasing the amount of liposomes in the background electrolyte significantly affected the separation kinetics of various active pharmaceutical ingredients, altering their mobility and/or peak shapes. Experiments with liposomes from bovine liver and heart tissue extracts revealed different interactions based on the lipid composition. Canagliflozin, which initially showed no electrophoretic mobility, migrated toward the anode in the presence of negatively charged liposomes. Mobility of positively charged substances, ambroxol and maraviroc, was suppressed by the interactions with liposomes. Their peaks also exhibited significant tailing. The effect on the separation of negatively charged compounds was significantly weaker. A small change in mobility was observed only in the case of deferasirox. We also examined the effect of temperature during separation, and we observed that increased temperature generally enhanced effective mobility due to lower electrolyte viscosity and increased lipid bilayer fluidity. Lastly, we tested the effect of sodium phosphate buffer pH (ranging from 6.0 to 8.0) with 4% liposomes on drug-liposome interactions. However, the effects were complex due to changes in API ionization and liposome surface charge, complicating the distinction between pH effects and liposome presence on API behavior. Our findings emphasize the significance of liposome composition, temperature, and pH in studying the interactions of liposomes with drugs, which is crucial for optimizing liposome-based drug delivery systems.

• Klíčová slova
• Active pharmaceutical ingredients, Capillary electrophoresis, Interactions, Liposomal electrokinetic chromatography, Liposomes, Pseudostationary phase,
• MeSH
• chromatografie micelární elektrokinetická kapilární * metody   MeSH
• koncentrace vodíkových iontů MeSH
• léčivé přípravky chemie   MeSH
• liposomy * chemie   MeSH
• skot MeSH
• teplota MeSH
• zvířata MeSH
• Check Tag
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• léčivé přípravky MeSH
• liposomy * MeSH

The permeation of small molecules across biological membranes is a crucial process that lies at the heart of life. Permeation is involved not only in the maintenance of homeostasis at the cell level but also in the absorption and biodistribution of pharmacologically active substances throughout the human body. Membranes are formed by phospholipid bilayers that represent an energy barrier for permeating molecules. Crossing this energy barrier is assumed to be a singular event, and permeation has traditionally been described as a first-order kinetic process, proportional only to the concentration gradient of the permeating substance. For a given membrane composition, permeability was believed to be a unique property dependent only on the permeating molecule itself. We provide experimental evidence that this long-held view might not be entirely correct. Liposomes were used in copermeation experiments with a fluorescent probe, where simultaneous permeation of two substances occurred over a single phospholipid bilayer. Using an assay of six commonly prescribed drugs, we have found that the presence of a copermeant can either enhance or suppress the permeation rate of the probe molecule, often more than 2-fold in each direction. This can have significant consequences for the pharmacokinetics and bioavailability of commonly prescribed drugs when used in combination and provide new insight into so-far unexplained drug-drug interactions as well as changing the perspective on how new drug candidates are evaluated and tested.

• Klíčová slova
• drug interaction, fluorescence quenching, liposomes, partitioning coefficient, permeability,
• MeSH
• buněčná membrána metabolismus   MeSH
• fluorescenční barviva farmakokinetika   chemie   MeSH
• fosfolipidy chemie   MeSH
• léky na předpis farmakokinetika   chemie   MeSH
• lidé MeSH
• lipidové dvojvrstvy metabolismus   MeSH
• liposomy * chemie   MeSH
• permeabilita MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fluorescenční barviva MeSH
• fosfolipidy MeSH
• léky na předpis MeSH
• lipidové dvojvrstvy MeSH
• liposomy * MeSH

Owing to their complicated pathophysiology, the treatment of skin diseases necessitates a complex approach. Conventional treatment using topical corticosteroids often results in low effectiveness and the incidence of local or even systemic side effects. Nanoformulation of potent anti-inflammatory drugs has been selected as an optimal strategy for enhanced topical delivery of corticosteroids. In order to assess the efficiency of various nanoformulations, we formulated hydrocortisone (HC) and hydrocortisone-17-butyrate (HCB) into three different systems: lipid nanocapsules (LNC), polymeric nanoparticles (PNP), and ethosomes (ETZ). The systems were characterized using dynamic light scattering for their particle size and uniformity and the morphology of nanoparticles was observed by transmission electron microscopy. The nanosystems were tested using ex vivo full thickness porcine and human skin for the delivery of HC and HCB. The skin penetration was observed by confocal microscopy of fluorescently labelled nanosystems. ETZ were proposed as the most effective delivery system for both transdermal and dermal drug targeting but were also found to have a profound effect on the skin barrier with limited restoration. LNC and PNP were found to have significant effects in the dermal delivery of the actives with only minimal transdermal penetration, especially in case of HCB administration.

• Klíčová slova
• PLGA nanoparticles, dermal and transdermal delivery, ethosomes, hydrocortisone, hydrocortisone-17-butyrate, lipid nanocapsules,
• Publikační typ
• časopisecké články MeSH