archives@tulane.edu / Transpapillary drug delivery is a novel drug administration technique that integrates the non-invasive, passive aspect of transdermal drug delivery with the targeted approach of intraductal drug delivery by capitalizing on the mammary ducts to serve as an entry point, conduit and reservoir. Although these channels have been identified as a primary transport route, their contribution to overall tissue penetration has not been quantified. By combining two fluorescence techniques, we were able to quantitatively assess the various transport routes of small molecules and drug delivery vehicles following in vitro diffusion.
Analysis of fluorescent images of porcine nipple cross-sections following diffusion of model hydrophilic and lipophilic fluorescent dyes indicated that both molecules penetrated the nipple via the stratum corneum and mammary ducts, however the lipophilic molecule targeted the ducts more so than the hydrophilic molecule. Encapsulating either dye within a liposome enhanced the ductal-associated fluorescence and reduced (hydrophilic dye) or did not affect (lipophilic dye) the stratum corneum-associated fluorescence. This suggests the capability of liposomes to selectively target and improve diffusion within the ductal channels. Encapsulation of the lipophilic dye within an oil-in-water nanoemulsion, however, either substantially increased penetration via both routes or only moderately improved transductal penetration, depending on the specific formulation.
The in vivo distribution and efficacy of transpapillary diffusion was evaluated by first establishing an intraductal estrogen receptor positive breast cancer model. Results from in vivo imaging elucidated two growth rates, either slow or fast, which were discernable 14 days post-injection. A pilot therapeutic efficacy study using 4-hydroxytamoxifen was then performed; however due to a small sample size, the results were inconclusive. In vivo transpapillary diffusion of a small, lipophilic molecule was confirmed, as illustrated following application of a fluorescent dye.
We conclude that transpapillary drug delivery is a viable in vitro administration technique for which the penetration routes can be tailored with drug carriers on a formulation-dependent basis. Furthermore, the feasibility of intraductally establishing estrogen receptor positive lesions and tracking their growth using in vivo imaging was validated. However, the use of this model to assess in vivo efficacy of transpapillary diffusion merits further evaluation. / 1 / Samantha Kurtz
| Identifer | oai:union.ndltd.org:TULANE/oai:http://digitallibrary.tulane.edu/:tulane_90931 |
| Date | January 2019 |
| Contributors | Kurtz, Samantha (author), Lawson, Louise (Thesis advisor), School of Science & Engineering Biomedical Engineering (Degree granting institution) |
| Publisher | Tulane University |
| Source Sets | Tulane University |
| Language | English |
| Detected Language | English |
| Type | Text |
| Format | electronic, pages: 166 |
| Rights | No embargo, Copyright is in accordance with U.S. Copyright law. |
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