12 research outputs found
Transpapillary (Nipple) Delivery of Macromolecules to the Breast: Proof of Concept Study
Localized
drug delivery to the breast can maximize drug concentration
at the target site and minimize systemic drug distribution. To this
end, the study explored the feasibility of delivering macromolecules
to the breast through mammary papilla (nipple). The in vitro penetration
of model macromolecules (inulin, dextran, ovalbumin, and bovine serum
albumin) varying in molecular weight from 5 to 67 kDa was studied
using excised porcine and human mammary papilla. The penetration of
macromolecules decreased with increase in molecular weight. The penetration
of the macromolecules was significantly higher through the mammary
papilla in comparison to breast skin. In vitro penetration of the
macromolecules was similar in human and porcine mammary papilla. Iontophoresis
was used to enhance the transport of bovine serum albumin (BSA) through
the mammary papilla. The flux and cumulative amount permeated was
increased by 2- to 4-fold by iontophoresis. The macromolecules were
transported through the ducts and the surrounding connective tissue
in the mammary papilla. Overall, the results from this study for the
first time demonstrate the feasibility of delivering macromolecules
through the mammary papilla. These findings have implications for
developing safe and effective localized therapeutic approaches for
breast cancer
Experimental set-up for in-vitro drug penetration study.
<p>Experimental set-up for in-vitro drug penetration study.</p
Permeation of 5-FU through excised breast tissue.
<p>In-vitro permeation of 5-FU through porcine (A) and human (B) nipple after removing the keratin plug (KR), nipple with keratin plug, and breast skin. Each data point is represented as mean ± SEM (n = 3–4). †is significant in comparison to the results from nipple with keratin plug; *is significant in comparison to skin. The values are significant at p<0.05, by one-way ANOVA.</p
In-vitro penetration parameters of 5-FU in porcine and human tissue.
<p>L is lag time; J<sub>ss</sub> is flux at steady state; Q<sub>48</sub> is cumulative amount of drug permeated per cm<sup>2</sup> of the tissue at 48 hrs; C<sub>T</sub> is tissue drug amount at 48 hrs. Results are presented as mean ± SEM (n = 3–4); ‘a’ is significant in comparison to porcine skin; ‘b’ is significant in comparison to human nipple with keratin plug; ‘c’ is significant in comparison to human skin. The values are significant at p<0.05 by one-way ANOVA.</p><p>In-vitro penetration parameters of 5-FU in porcine and human tissue.</p
Transpapillary Drug Delivery to the Breast
<div><p>The study was aimed at investigating localized topical drug delivery to the breast via mammary papilla (nipple). 5-fluorouracil (5-FU) and estradiol (EST) were used as model hydrophilic and hydrophobic compounds respectively. Porcine and human nipple were used for in-vitro penetration studies. The removal of keratin plug enhanced the drug transport through the nipple. The drug penetration was significantly higher through the nipple compared to breast skin. The drug’s lipophilicity had a significant influence on drug penetration through nipple. The ducts in the nipple served as a major transport pathway to the underlying breast tissue. Results showed that porcine nipple could be a potential model for human nipple. The topical application of 5-FU on the rat nipple resulted in high drug concentration in the breast and minimal drug levels in plasma and other organs. Overall, the findings from this study demonstrate the feasibility of localized drug delivery to the breast through nipple.</p></div
Fluorescence microscopic images of nipple.
<p>Fluorescence microscopic images of 7–8 µm thick cryosections of porcine (A) and human (B) nipple after treatment with the fluorescent dyes, SRB (upper panel in A and B) and NR (lower panel in A and B). Sections were taken from the entire length of the nipple starting from the tip to the base of the nipple. (Bar = 100 µm); SRB- sulforhodamine; NR- Nile red.</p
Confocal microscopic images of porcine nipple.
<p>(A) Cross section of porcine nipple after staining with hematoxylin-eosin. (Bar = 200 µm), (B) Confocal laser scanning microscopic images of porcine nipple, after treatment with hydrophilic dye sulforhodamine (SRB; upper panel) and hydrophobic dye Nile red (NR; lower panel). Image on the left panel is a cumulative xyz image of optical sections from 0 to 500 µm in the tissue. Images on the right panel are xz images from 0 to 500 µm (Bar = 100 µm).</p
Biodistribution of 5-FU in plasma and organs in rat.
<p>Ratio of amount of 5-FU in rat organs or plasma (5-FU<sub>O/P</sub>) and amount of 5-FU in mammary gland (5-FU<sub>MG</sub>) after topical (nipple), transdermal (breast skin) and intravenous administration. Each value is represented as mean ± SD (n = 3); * is significant in comparison to intravenous injection group. The values are significant at p<0.05, by one-way ANOVA. MP- topical application on the mammary papilla (nipple); TD- transdermal delivery; IV-intravenous injection. The drug was applied on the mammary papilla or on the breast skin for 2 hrs or 6 hrs. In case of disposition studies, the drug was removed after 6 hrs treatment and the drug concentration in the plasma and organs were measured at 12 hrs.</p
Experimental set-up for topical application of 5-FU on nipple in-vivo.
<p>(A) Adhesive tape was applied around nipple to limit the topical drug delivery through the nipple; (B) Hilltop chamber was used for topical drug application.</p
In-vitro penetration parameters of EST in porcine and human tissue.
<p>L is lag time; J<sub>ss</sub> is flux at steady state; Q<sub>48</sub> is cumulative amount of drug permeated per cm<sup>2</sup> of the tissue at 48 hrs; C<sub>T</sub> is tissue drug amount at 48 hrs. Results are presented as mean ± SEM (n = 3–4); ‘a’ is significant in comparison to porcine nipple with keratin plug; ‘b’ is significant in comparison to porcine skin; ‘c’ is significant in comparison to human nipple with keratin plug; ‘d’ is significant in comparison to human skin. The values are significant at p<0.05 by one-way ANOVA.</p><p>In-vitro penetration parameters of EST in porcine and human tissue.</p