Influence of molecular size on the retention of polymeric nanocarrier diagnostic agents in breast ducts.

Pharmaceutical Research
Yashveer SinghPatrick J Sinko

Abstract

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 (t(1/2)). Plasma samples were taken and the pharmacokinetics (Tmax, Cmax) of absorbed nanocarriers was also assessed. 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. Since normal breast ducts are highly permeable, the use of nanocarriers may be helpful in prolonging ductal retention of diagnostic and/or therapeutic agents.

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Citations

Oct 29, 2013·Annual Review of Pharmacology and Toxicology·Matthew PalomboPatrick J Sinko
Sep 17, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Sujata Sundara RajanPatrick J Sinko
Sep 23, 2016·Bioconjugate Chemistry·Eric L SchneiderDaniel V Santi
Sep 4, 2018·Translational Vision Science & Technology·Nobuo MachinagaDaniel V Santi
Aug 16, 2019·Scientific Reports·Samantha L Kurtz, Louise B Lawson
Nov 22, 2012·Cancer Prevention Research·Susan M LoveBaoning Zhang
Jul 20, 2021·Advanced Drug Delivery Reviews·José das NevesBruno Sarmento
Mar 6, 2019·Molecular Pharmaceutics·Samantha L Kurtz, Louise B Lawson
Dec 19, 2018·Bioconjugate Chemistry·Mozhdeh ImaninezhadSilviya Petrova Zustiak

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