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Multifunctional nanoemulsions for intraductal delivery as a new platform for local treatment of breast cancer.

ABSTRACT: Considering that breast cancer usually begins in the lining of the ducts, local drug administration into the ducts could target cancers and pre-tumor lesions locally while reducing systemic adverse effects. In this study, a cationic bioadhesive nanoemulsion was developed for intraductal administration of C6 ceramide, a sphingolipid that mediates apoptotic and non-apoptotic cell death. Bioadhesive properties were obtained by surface modification with chitosan. The optimized nanoemulsion displayed size of 46.3 nm and positive charge, properties that were not affected by ceramide encapsulation (0.4%, w/w). C6 ceramide concentration necessary to reduce MCF-7 cells viability to 50% (EC50) decreased by 4.5-fold with its nanoencapsulation compared to its solution; a further decrease (2.6-fold) was observed when tributyrin (a pro-drug of butyric acid) was part of the oil phase of the nanocarrier, a phenomenon attributed to synergism. The unloaded nanocarrier was considered safe, as indicated by a score <0.1 in HET-CAM models, by the high survival rates of Galleria mellonella larvae exposed to concentrations ≤500 mg/mL, and absence of histological changes when intraductally administered in rats. Intraductal administration of the nanoemulsion prolonged drug localization for more than 120 h in the mammary tissue compared to its solution. These results support the advantage of the optimized nanoemulsion to enable mammary tissue localization of C6 ceramide.

SUBMITTER: Migotto A

PROVIDER: S-EPMC7011997 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Multifunctional nanoemulsions for intraductal delivery as a new platform for local treatment of breast cancer.

Migotto Amanda A Carvalho Vanessa F M VFM Salata Giovanna C GC da Silva Fernanda W M FWM Yan Chao Yun Irene CYI Ishida Kelly K Costa-Lotufo Leticia V LV Steiner Alexandre A AA Lopes Luciana B LB Lopes Luciana B LB

Drug delivery 20181101 1

Considering that breast cancer usually begins in the lining of the ducts, local drug administration into the ducts could target cancers and pre-tumor lesions locally while reducing systemic adverse effects. In this study, a cationic bioadhesive nanoemulsion was developed for intraductal administration of C6 ceramide, a sphingolipid that mediates apoptotic and non-apoptotic cell death. Bioadhesive properties were obtained by surface modification with chitosan. The optimized nanoemulsion displayed ...[more]

PMID: 29495885

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Project description:BackgroundBreast-conserving surgery and mastectomy are standard surgical options for breast cancer. However, some patients experience a local recurrence after the operation. Many factors have been identified as a risk of local recurrence. Extensive intraductal component (EIC) was found as one of the major risks of the recurrence. Nevertheless, there were neither any systematic reviews nor controlled trials focused on EIC. This study aims to identify the impact of EIC on the local recurrence of breast cancer.MethodsWe searched all relevant studies published between the inception to December 2020. All electronic data from PubMed and Scopus databases were extracted for evaluation of EIC as a factor of the recurrence. Local recurrence was a primary outcome between EIC-positive group and EIC-negative group. Margin status and adjuvant radiation were focused as a subgroup analysis. The Newcastle Ottawa Scale was applied for quality assessment of included studies and RevMan 5.3 program was used to estimate the effect of the results. The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.ResultsA total of 32 studies, comprising 4,290 and 15,143 patients in the EIC-positive and EIC-negative groups respectively, were retrieved and met selection criteria. All included studies were at low to intermediate risk of bias. There was a statistically significant difference in local recurrence between EIC-positive patients and EIC-negative patients (OR =2.73; 95% CI: 2.42-3.07; P<0.00001). However, there was not any significant difference in patients who had negative margin (OR =1.97; 95% CI: 0.92-4.19; P=0.36) or received any adjuvant irradiation (OR =1.58; 95% CI: 0.55-4.54; P=0.24).ConclusionsEIC increases the risk of local recurrence, especially in breast-conserving surgery patients. However, there are a limited number of populations to analyze in subgroup analysis, the rate of local recurrence between two groups is not different in patients who had negative margin or received postoperative irradiation.

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Multifunctional nanoemulsions for intraductal delivery as a new platform for local treatment of breast cancer.

Publications

Multifunctional nanoemulsions for intraductal delivery as a new platform for local treatment of breast cancer.

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