title: Aptamer-based liposomes improve specific drug loading and release.
abstract: Aptamer technology has shown much promise in cancer therapeutics for its targeting abilities. However, its potential to improve drug loading and release from nanocarriers has not been thoroughly explored. In this study, we employed drug-binding aptamers to actively load drugs into liposomes. We designed a series of DNA aptamer sequences specific to doxorubicin, displaying multiple binding sites and various binding affinities. The binding ability of aptamers was preserved when incorporated into cationic liposomes, binding up to 15equivalents of doxorubicin per aptamer, therefore drawing the drug into liposomes. Optimization of the charge and drug/aptamer ratios resulted in ≥80% encapsulation efficiency of doxorubicin, ten times higher than classical passively-encapsulating liposomal formulations and similar to a pH-gradient active loading strategy. In addition, kinetic release profiles and cytotoxicity assay on HeLa cells demonstrated that the release and therapeutic efficacy of liposomal doxorubicin could be controlled by the aptamer's structure. Our results suggest that the aptamer exhibiting a specific intermediate affinity is the best suited to achieve high drug loading while maintaining efficient drug release and therapeutic activity. This strategy was successfully applied to tobramycin, a hydrophilic drug suffering from low encapsulation into liposomes, where its loading was improved six-fold using aptamers. Overall, we demonstrate that aptamers could act, in addition to their targeting properties, as multifunctional excipients for liposomal formulations.
authors.affiliation: Faculty of Pharmacy, University of Montreal, QC H3T 1J4, Canada.
authors.forename: Kevin
authors.initials: K
authors.lastname: Plourde
authors.affiliation: Faculty of Pharmacy, University of Montreal, QC H3T 1J4, Canada.
authors.forename: Rabeb Mouna
authors.initials: RM
authors.lastname: Derbali
authors.affiliation: Department of Chemistry, University of Montreal, QC H3T 1J4, Canada.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Desrosiers
authors.affiliation: Faculty of Pharmacy, University of Montreal, QC H3T 1J4, Canada.
authors.forename: Céline
authors.initials: C
authors.lastname: Dubath
authors.affiliation: Department of Chemistry, University of Montreal, QC H3T 1J4, Canada.
authors.forename: Alexis
authors.initials: A
authors.lastname: Vallée-Bélisle
authors.affiliation: Faculty of Pharmacy, University of Montreal, QC H3T 1J4, Canada. Electronic address: Jeanne.leblond-chain@umontreal.ca.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Leblond
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D052157:Aptamers, Nucleotide / Q000737:chemistry*; D002470:Cell Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004355:Drug Stability; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008081:Liposomes / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D008081:Liposomes; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: Active loading; Aptamer; Controlled release; Doxorubicin; Encapsulation efficiency; Liposome