title: One Step Encapsulation of Small Molecule Drugs in Liposomes via Electrospray-Remote Loading.
abstract: Resiquimod is a Toll-like receptor (TLR) 7/8 agonist that has previously been used as a vaccine adjuvant, as a topical treatment of viral lesions and skin cancer, and as an antiviral treatment. We report on the combined application of remote loading and electrospray to produce liposomal resiquimod, with the broader goals of improving drug encapsulation efficiency and scalability of liposome production methods. Drug loading in liposomes increased from less than 1% to greater that 3% by mass when remote loading was used, whether the liposomes were generated by thin-film hydration or electrospray methods. Dynamic light scattering (DLS) determined mean vesicle diameters of 137 ± 11 nm and 103 ± 4 for the thin-film and electrospray methods, respectively. Transmission electron microscopy (TEM) images showed spherical vesicles with sizes consistent with the DLS measurements. In vitro drug release profiles found that most of the drug remained within the liposomes at both pH 5.5 and 7.4. The in vitro bioactivity of the liposomal drug was also demonstrated by the increase in nitrite production when RAW macrophages were exposed to the drug. Our findings indicate that the remotely loaded liposomes formed via the scalable electrospray method have characteristics comparable to those produced via conventional batch methods. The methods discussed here are not limited to the enhanced delivery of resiquimod. Rather, they should be readily adaptable to other compounds compatible with remote loading.
authors.affiliation: William G. Lowrie Department of Chemical and Biomolecular Engineering, College of Engineering, The Ohio State University , Columbus, Ohio 43210, United States.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Duong
authors.affiliation: Division of Molecular Pharmaceutics, College of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Collier
authors.affiliation: Division of Molecular Pharmaceutics, College of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Bachelder
authors.affiliation: William G. Lowrie Department of Chemical and Biomolecular Engineering, College of Engineering, The Ohio State University , Columbus, Ohio 43210, United States.|Department of Chemistry and Biochemistry, College of Arts and Sciences, The Ohio State University , Columbus, Ohio 43210, United States.
authors.forename: Barbra E
authors.initials: BE
authors.lastname: Wyslouzil
authors.affiliation: Division of Molecular Pharmaceutics, College of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
authors.forename: Kristy M
authors.initials: KM
authors.lastname: Ainslie
mesh_terms: D002626:Chemistry, Pharmaceutical; D000067493:Dynamic Light Scattering; D004563:Electrochemistry; D008081:Liposomes / Q000737:chemistry*; D008567:Membranes, Artificial; D046529:Microscopy, Electron, Transmission
chemical_list: D008081:Liposomes; D008567:Membranes, Artificial
keywords: electrospray; remote load; resiquimod; scalable; thin film