title: Control of polymeric nanoparticle size to improve therapeutic delivery.
abstract: As nanoparticle (NP)-mediated drug delivery research continues to expand, understanding parameters that govern NP interactions with the biological environment becomes paramount. The principles identified from the study of these parameters can be used to engineer new NPs, impart unique functionalities, identify novel utilities, and improve the clinical translation of NP formulations. One key design parameter is NP size. New methods have been developed to produce NPs with increased control of NP size between 10 and 200nm, a size range most relevant to physical and biochemical targeting through both intravascular and site-specific deliveries. Three notable techniques best suited for generating polymeric NPs with narrow size distributions are highlighted in this review: self-assembly, microfluidics-based preparation, and flash nanoprecipitation. Furthermore, the effect of NP size on the biological fate and transport properties at the molecular scale (protein-NP interactions) and the tissue and systemic scale (convective and diffusive transport of NPs) are analyzed here. These analyses underscore the importance of NP size control in considering clinical translation and assessment of therapeutic outcomes of NP delivery vehicles.
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD 21205, United States; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, United States; Institute for Cell Engineering, Johns Hopkins School of Medicine, Baltimore, MD 21205, United States; Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD 21287, United States.
authors.forename: John W
authors.initials: JW
authors.lastname: Hickey
authors.affiliation: Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, United States; Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD 21287, United States; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, United States.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Santos
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD 21205, United States; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, United States; Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD 21287, United States.
authors.forename: John-Michael
authors.initials: JM
authors.lastname: Williford
authors.affiliation: Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, United States; Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD 21287, United States; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, United States; Whitaker Biomedical Engineering Institute, Johns Hopkins University, Baltimore, MD 21218, United States. Electronic address: hmao@jhu.edu.
authors.forename: Hai-Quan
authors.initials: HQ
authors.lastname: Mao
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D011108:Polymers
keywords: Drug delivery; Nanomedicine; Polymeric nanoparticles; Size control