title: Influence of molecular size on the retention of polymeric nanocarrier diagnostic agents in breast ducts.
abstract: OBJECTIVE
  To investigate the influence of nanocarrier molecular size and shape on breast duct retention in normal rats using a non-invasive optical imaging method.
  
  
  METHODS
  Fluorescein-labeled PEG nanocarriers of different molecular weights and shapes (linear, two-arm, four-arm, and eight-arm) were intraductally administered (50 nmol) to female Sprague-Dawley rats. Whole body images were obtained non-invasively. Fluorescence intensities (i.e., amount remaining in duct) were plotted against time to estimate the nanocarrier ductal retention half-lives (t(1/2)). Plasma samples were taken and the pharmacokinetics (Tmax, Cmax) of absorbed nanocarriers was also assessed.
  
  
  RESULTS
  The t(1/2) of linear 12, 20, 30, 40, and two-arm 60 kDa nanocarriers were 6.7 ± 0.9, 16.1 ± 4.1, 16.6 ± 3.4, 21.5 ± 2.7, and 19.5 ± 6.1 h, whereas the four-arm 20, 40, and eight-arm 20 kDa had t(1/2) of 9.0 ± 0.5, 11.5 ± 1.9, and 12.6 ± 3.0 h. The t(1/2) of unconjugated fluorescein was significantly lower (14.5 ± 1.4 min). The Tmax for 12, 40, 60 kDa nanocarriers were 1, 24, and 32 h, respectively, and only 30 min for fluorescein.
  
  
  CONCLUSIONS
  Since normal breast ducts are highly permeable, the use of nanocarriers may be helpful in prolonging ductal retention of diagnostic and/or therapeutic agents.
authors.affiliation: Department of Pharmaceutics Ernest Mario School of Pharmacy, Rutgers The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey 08854, USA.
authors.forename: Yashveer
authors.initials: Y
authors.lastname: Singh
authors.forename: Dayuan
authors.initials: D
authors.lastname: Gao
authors.forename: Zichao
authors.initials: Z
authors.lastname: Gu
authors.forename: Shike
authors.initials: S
authors.lastname: Li
authors.forename: Kristia A
authors.initials: KA
authors.lastname: Rivera
authors.forename: Stanley
authors.initials: S
authors.lastname: Stein
authors.forename: Susan
authors.initials: S
authors.lastname: Love
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Sinko
mesh_terms: D000818:Animals; D005260:Female; D019793:Fluorescein / Q000737:chemistry; D006207:Half-Life; D008325:Mammary Neoplasms, Experimental / Q000175:diagnosis*; D053758:Nanoparticles; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011108:Polymers / Q000737:chemistry*; D017207:Rats, Sprague-Dawley
chemical_list: D011108:Polymers; D011092:Polyethylene Glycols; D019793:Fluorescein