期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 567, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2019.118460
关键词
Nanoemulsion; Bioadhesion; Breast cancer; Piplartine; Intraductal delivery
资金
- Sao Paulo Research Foundation (FAPESP) [2013/16617-7, 2018/03418-0, 2018/13877-1]
- National Council of Technological and Scientific Development (CNPq) [443549/2014-1]
- CNPQ
- CAPES [001]
- FAPESP [2017/04174-4, 2017/23213-0, 2017/19059-6, 2018/18813-1]
As a new strategy for treatment of ductal carcinoma in situ, biocompatible and bioadhesive nanoemulsions for intraductal administration of the cytotoxic agent piplartine (piperlongumine) were optimized in this study. To confer bioadhesive properties, the nanoemulsion was modified with chitosan or hyaluronic acid. Tricaprylin was selected as the nanoemulsion non-polar phase due to its ability to dissolve larger drug amounts compared to isopropyl myristate and monocaprylin. Use of phosphatidylcholine as sole surfactant did not result in a homogeneous nanoemulsion, while its association with polysorbate 80 and glycerol (in a surfactant blend) led to the formation of nanoemulsions with droplet size of 76.5 +/- 1.2 nm. Heating the aqueous phase to 50 degrees C enabled sonication time reduction from 20 to 10 min. Inclusion of either chitosan or hyaluronic acid resulted in nanoemulsions with similar in vitro bioadhesive potential, and comparable ability to prolong mammary tissue retention (to 120 h) in vivo without causing undesirable histological alterations. Piplartine was stable in both nanoemulsions for 60 days; however, the size of loaded NE-HA was maintained at a similar range for longer periods of time, suggesting that this nanoemulsion may be a stronger candidate for intraductal delivery.
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