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Influence of Molecular Size on the Retention of Polymeric Nanocarrier Diagnostic Agents in Breast Ducts

2012; Springer Science+Business Media; Volume: 29; Issue: 9 Linguagem: Inglês

10.1007/s11095-012-0763-z

1573-904X

Yashveer Singh, Dayuan Gao, Zichao Gu, Shike Li, Kristia Alejandra Rivera, Stanley J. Stein, Susan M. Love, Patrick J. Sinko,

Optical Imaging and Spectroscopy Techniques

To investigate the influence of nanocarrier molecular size and shape on breast duct retention in normal rats using a non-invasive optical imaging method. 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 (t1/2). Plasma samples were taken and the pharmacokinetics (Tmax, Cmax) of absorbed nanocarriers was also assessed. The t1/2 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 t1/2 of 9.0 ± 0.5, 11.5 ± 1.9, and 12.6 ± 3.0 h. The t1/2 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. Since normal breast ducts are highly permeable, the use of nanocarriers may be helpful in prolonging ductal retention of diagnostic and/or therapeutic agents.