title: Langmuir monolayers and Differential Scanning Calorimetry for the study of the interactions between camptothecin drugs and biomembrane models.
abstract: CPT-11 and SN-38 are camptothecins with strong antitumor activity. Nevertheless, their severe side effects and the chemical instability of their lactone ring have questioned the usual forms for its administration and have focused the current research on the development of new suitable pharmaceutical formulations. This work presents a biophysical study of the interfacial interactions of CPT-11 and SN-38 with membrane mimetic models by using monolayer techniques and Differential Scanning Calorimetry. The aim is to get new insights for the understanding of the bilayer mechanics after drug incorporation and to optimize the design of drug delivery systems based on the formation of stable bilayer structures. Moreover, from our knowledge, the molecular interactions between camptothecins and phospholipids have not been investigated in detail, despite their importance in the context of drug action. The results show that neither CPT-11 nor SN-38 disturbs the structure of the complex liposome bilayers, despite their different solubility, that CPT-11, positively charged in its piperidine group, interacts electrostatically with DOPS, making stable the incorporation of a high percentage of CPT-11 into liposomes and that SN-38 establishes weak repulsive interactions with lipid molecules that modify the compressibility of the bilayer without affecting significantly neither the lipid collapse pressure nor the miscibility pattern of drug-lipid mixed monolayers. The suitability of a binary and a ternary lipid mixture for encapsulating SN-38 and CPT-11, respectively, has been demonstrated.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Av. Diagonal 643, 08028 Barcelona, Spain. Electronic address: ancasado@clinic.ub.es.
authors.forename: Ana
authors.initials: A
authors.lastname: Casadó
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Av. Diagonal 643, 08028 Barcelona, Spain; Department of Drug Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy. Electronic address: mcgiuffrida@gmail.com.
authors.forename: M Chiara
authors.initials: MC
authors.lastname: Giuffrida
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Av. Diagonal 643, 08028 Barcelona, Spain. Electronic address: mlsagrista@ub.edu.
authors.forename: M Lluïsa
authors.initials: ML
authors.lastname: Sagristá
authors.affiliation: Department of Drug Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy. Electronic address: fcastelli@unict.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Castelli
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain. Electronic address: mopujol@ub.edu.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Pujol
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain. Electronic address: aalsina@ub.edu.
authors.forename: M Asunción
authors.initials: MA
authors.lastname: Alsina
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Av. Diagonal 643, 08028 Barcelona, Spain. Electronic address: margarita.mora@ub.edu.
authors.forename: Margarita
authors.initials: M
authors.lastname: Mora
mesh_terms: D040761:Biomimetic Materials / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry; D000077146:Irinotecan; D008567:Membranes, Artificial
chemical_list: D008567:Membranes, Artificial; D000077146:Irinotecan; D002166:Camptothecin
keywords: Bilayer systems; Biomembrane models; Camptothecins; Langmuir monolayers; Liposomes; Membrane interactions