title: Strategies for improving the intratumoral distribution of liposomal drugs in cancer therapy.
abstract: BACKGROUND
  A major limitation of current liposomal cancer therapies is the inability of liposome therapeutics to penetrate throughout the entire tumor mass. This inhomogeneous distribution of liposome therapeutics within the tumor has been linked to treatment failure and drug resistance. Both liposome particle transport properties and tumor microenvironment characteristics contribute to this challenge in cancer therapy. This limitation is relevant to both intravenously and intratumorally administered liposome therapeutics.
  
  
  METHODS
  Strategies to improve the intratumoral distribution of liposome therapeutics are described. Combination therapies of intravenous liposome therapeutics with pharmacologic agents modulating abnormal tumor vasculature, interstitial fluid pressure, extracellular matrix components, and tumor associated macrophages are discussed. Combination therapies using external stimuli (hyperthermia, radiofrequency ablation, magnetic field, radiation, and ultrasound) with intravenous liposome therapeutics are discussed. Intratumoral convection-enhanced delivery (CED) of liposomal therapeutics is reviewed.
  
  
  CONCLUSIONS
  Optimization of the combination therapies and drug delivery protocols are necessary. Further research should be conducted in appropriate cancer types with consideration of physiochemical features of liposomes and their timing sequence. More investigation of the role of tumor associated macrophages in intratumoral distribution is warranted. Intratumoral infusion of liposomes using CED is a promising approach to improve their distribution within the tumor mass.
authors.affiliation: a Department of Radiology , University of Texas Health Science Center San Antonio , San Antonio , TX , USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Goins
authors.affiliation: a Department of Radiology , University of Texas Health Science Center San Antonio , San Antonio , TX , USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Phillips
authors.affiliation: b Department of Radiation Oncology, School of Medicine, Case Western Reserve University/University Hospitals Case Medical Center , Cleveland , OH , USA.
authors.forename: Ande
authors.initials: A
authors.lastname: Bao
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D006801:Humans; D008081:Liposomes; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D008081:Liposomes
keywords: Convection enhanced delivery; drug delivery; imaging; intratumoral administration; intratumoral distribution; liposomes; nanoparticles; tumor penetration