title: State-of-the-art in design rules for drug delivery platforms: lessons learned from FDA-approved nanomedicines.
abstract: The ability to efficiently deliver a drug to a tumor site is dependent on a wide range of physiologically imposed design constraints. Nanotechnology provides the possibility of creating delivery vehicles where these design constraints can be decoupled, allowing new approaches for reducing the unwanted side effects of systemic delivery, increasing targeting efficiency and efficacy. Here we review the design strategies of the two FDA-approved antibody-drug conjugates (Brentuximab vedotin and Trastuzumab emtansine) and the four FDA-approved nanoparticle-based drug delivery platforms (Doxil, DaunoXome, Marqibo, and Abraxane) in the context of the challenges associated with systemic targeted delivery of a drug to a solid tumor. The lessons learned from these nanomedicines provide an important insight into the key challenges associated with the development of new platforms for systemic delivery of anti-cancer drugs.
authors.affiliation: Institute for Nanobiotechnology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA; Johns Hopkins Center of Cancer Nanotechnology Excellence, 100 Croft Hall, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.; Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
authors.forename: Charlene M
authors.initials: CM
authors.lastname: Dawidczyk
authors.affiliation: Institute for Nanobiotechnology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA; Johns Hopkins Center of Cancer Nanotechnology Excellence, 100 Croft Hall, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.; Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
authors.forename: Chloe
authors.initials: C
authors.lastname: Kim
authors.affiliation: Institute for Nanobiotechnology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA; Johns Hopkins Center of Cancer Nanotechnology Excellence, 100 Croft Hall, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.; Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
authors.forename: Jea Ho
authors.initials: JH
authors.lastname: Park
authors.affiliation: Institute for Nanobiotechnology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA; Johns Hopkins Center of Cancer Nanotechnology Excellence, 100 Croft Hall, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.; Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Russell
authors.affiliation: KIST Biomedical Research Institute, 5 Hwarangno 14-gil, Seongbuk-gu, Seoul 136-791, Republic of Korea.
authors.forename: Kwan Hyi
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Institute for Nanobiotechnology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA; Johns Hopkins Center of Cancer Nanotechnology Excellence, 100 Croft Hall, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA. Electronic address: mpomper@jhmi.edu.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
authors.affiliation: Institute for Nanobiotechnology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA; Johns Hopkins Center of Cancer Nanotechnology Excellence, 100 Croft Hall, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.; Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA. Electronic address: searson@jhu.edu.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Searson
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D017277:Drug Approval; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage; D050997:Nanomedicine; D053758:Nanoparticles / Q000008:administration & dosage; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents; D018796:Immunoconjugates
keywords: Active targeting; Circulation; Enhanced permeability and retention (EPR) effect; Liposomes; Nanoparticles; Tumor targeting