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

Author(s)

Carvalho, Vanessa F. M. ^[1] ; Salata, Giovanna C. ^[1] ; de Matos, Jenyffer K. R. ^[1] ; Costa-Fernandez, Sandra ^[1] ; Chorilli, Marlus ^[2] ; Steiner, Alexandre A. ^[3] ; de Araujo, Gabriel L. B. ^[4] ; Silveira, Edilberto R. ^[5] ; Costa-Lotufo, V, Leticia ; Lopes, Luciana B. ^[6]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Av Prof Lineu Presses 1524, Sao Paulo, SP - Brazil

^[2] Sao Paulo State Univ, Sch Pharmaceut Sci Araraquara, Araraquara, SP - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Sch Pharmaceut Sci, Sao Paulo, SP - Brazil

^[5] Univ Fed Ceara, Dept Inorgan & Organ Chem, Fortaleza, Ceara - Brazil

^[6] Costa-Lotufo, Leticia, V, Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Av Prof Lineu Presses 1524, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: International Journal of Pharmaceutics; v. 567, AUG 15 2019.
• Web of Science Citations: 2

Abstract

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. (AU)

• FAPESP's process: 17/23213-0 - Biorresponsive systems for sustained drug release and breast cancer chemoprevention
• Grantee: Giovanna Cassone Salata
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 13/16617-7 - Nanostructured systems for topical delivery and co-localization of chemopreventive and chemoterapeutic agents in the skin and breast tissue
• Grantee: Luciana Biagini Lopes
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 17/04174-4 - Development and evaluation of cationic bioadhesive nanocarriers as a platform to localize piplartine in the breast for tumor treatment
• Grantee: Vanessa Franco Carvalho Dartora
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/03418-0 - Hypothermia in Sepsis: causes and consequences
• Grantee: Alexandre Alarcon Steiner
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/18813-1 - Bioresponsive gels containing nanoparticles for exudate control and co-delivery of propranolol and adenosine for wound healing applications
• Grantee: Jenyffer Kelly Rocha de Matos
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 18/13877-1 - Nanocarriers for localized treatment and chemoprevention of breast tumors
• Grantee: Luciana Biagini Lopes
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2