Optimization of composition and obtainment parameters of biocompatible nanoemulsions intended for intraductal administration of piplartine (piperlongumine) and mammary tissue targeting

Made available in DSpace on 2019-10-06T05:45:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-08-15 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) 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. Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Av Prof Lineu Presses 1524, Sao Paulo, SP, Brazil Sao Paulo State Univ, Sch Pharmaceut Sci Araraquara, Araraquara, SP, Brazil Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo, SP, Brazil Univ Sao Paulo, Sch Pharmaceut Sci, Sao Paulo, SP, Brazil Univ Fed Ceara, Dept Inorgan & Organ Chem, Fortaleza, Ceara, Brazil Sao Paulo State Univ, Sch Pharmaceut Sci Araraquara, Araraquara, SP, Brazil FAPESP: 2013/16617-7 FAPESP: 2018/03418-0 FAPESP: 2018/13877-1 CNPq: 443549/2014-1 CAPES: 001 FAPESP: 2017/04174-4 FAPESP: 2017/23213-0 FAPESP: 2017/19059-6 FAPESP: 2018/18813-1