title: Effect of piroxicam on lipid membranes: Drug encapsulation and gastric toxicity aspects.
abstract: Uptake of piroxicam, a non-steroidal anti-inflammatory drug, from the intestines after oral intake is limited due to its low solubility and its wide use is associated with several side effects related to the gastrointestinal tract. In this study, all-atom molecular dynamics (MD) simulations and fluorescent spectroscopy were employed to investigate the interaction of piroxicam in neutral, zwitterionic, and cationic forms with lipid bilayers composed of phosphatidylcholine, cholesterol, and PEGylated lipids. Our study was aimed to assess the potential for encapsulation of piroxicam in liposomal carriers and to shed more light on the process of gastrointestinal tract injury by the drug. Through both the MD simulations and laser scanning confocal microscopy, we have demonstrated that all forms of piroxicam can associate with the lipid bilayers and locate close to the water-membrane interface. Conventional liposomes used in drug delivery are usually stabilized by the addition of cholesterol and have their bloodstream lifetime extended through the inclusion of PEGylated lipids in the formulation to create a protective polymer corona. For this reason, we tested the effect of these two modifications on the behavior of piroxicam in the membrane. When the bilayer was PEGylated, piroxicam localize to the PEG layer and within the lipid headgroup region. This suggests that PEGylated liposomes are capable of carrying a larger quantity of piroxicam than the conventional ones.
authors.affiliation: Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Kraków, Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Wilkosz
authors.affiliation: Department of Physics, Tampere University of Technology, PO Box 692, FI-33101 Tampere, Finland.
authors.forename: Sami
authors.initials: S
authors.lastname: Rissanen
authors.affiliation: Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Kraków, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Cyza
authors.affiliation: Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Kraków, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Szybka
authors.affiliation: Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Kraków, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Nowakowska
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki 00100, Finland.
authors.forename: Alex
authors.initials: A
authors.lastname: Bunker
authors.affiliation: Department of Physics, Tampere University of Technology, PO Box 692, FI-33101 Tampere, Finland; Department of Physics, University of Helsinki, Gustaf Hällströmin katu 2a, FI-00560 Helsinki, Finland. Electronic address: tomasz.rog@gmail.com.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Róg
authors.affiliation: Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Kraków, Poland. Electronic address: kepczyns@chemia.uj.edu.pl.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Kepczynski
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D016503:Drug Delivery Systems; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes; D056004:Molecular Dynamics Simulation; D010894:Piroxicam / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D013270:Stomach / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008051:Lipid Bilayers; D008081:Liposomes; D010894:Piroxicam
keywords: 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (PubChem CID: 5497103); Cholesterol (PubChem CID: 5997); Gastric toxicity; Lipid bilayer; MD simulations; N-(Carbonyl-methoxypoly(ethylene glycol) 2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine, sodium salt (PubChem CID: 86278269); NSAIDs; PEGylated liposomes; Piroxicam; Piroxicam (PubChem CID: 54676228)