title: Formulation and physiologic factors affecting the pharmacology of carrier-mediated anticancer agents.
abstract: BACKGROUND
  Major advances in carrier-mediated agents (CMAs), which include nanoparticles and conjugates, have revolutionized drug delivery capabilities over the past decade. While providing numerous advantages such as increased exposure duration, greater solubility and delivery to tumor sites over their small molecule counterparts, there is substantial variability in how individual CMA formulations affect the pharmacology, pharmacokinetics and pharmacodynamics (efficacy and toxicity) of these agents.
  
  
  METHODS
  CMA formulations are complex in nature compared to their small molecule counterparts and consist of multiple components and variables that can affect the pharmacological profile. This review provides an overview of factors that affect the pharmacologic profiles observed in CMA-formulated chemotherapy, primarily in liposomal formulations, that are currently in preclinical or early clinical development.
  
  
  CONCLUSIONS
  Despite the numerous advantages that CMA formulations provide, their clinical use is still in its infancy. It is critical that we understand the mechanisms and effects of CMAs in navigating biological barriers and how these factors affect their biodistribution and delivery to tumors. Future studies are warranted to better understand the complex pharmacology and interaction between CMA carriers and biological systems, such as the mononuclear phagocyte system and tumor microenvironment.
authors.affiliation: a 1 University of North Carolina at Chapel Hill (UNC), Eshelman School of Pharmacy, Division of Pharmacotherapy and Experimental Therapeutics , 120 Mason Farm Road, suite 1022B, CB 7361, Chapel Hill, NC 27599-7361, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Lucas
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Madden
authors.forename: William C
authors.initials: WC
authors.lastname: Zamboni
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D008081:Liposomes; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012995:Solubility; D014018:Tissue Distribution; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes
keywords: carrier-mediated agents; chemotherapy; drug delivery; mononuclear phagocyte system; nanomedicine; nanoparticles; tumor targeting