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3 results on '"Intraductal delivery"'

1. Systemic and Local Strategies for Primary Prevention of Breast Cancer.

Author

Zaluzec, Erin K. and Sempere, Lorenzo F.

Subjects
*BRCA genes, *CARCINOGENESIS, *TRANSDERMAL medication, *DRUG administration, *EPITHELIAL cells, *MASTECTOMY, BREAST tumor prevention
Abstract

Simple Summary: Current interventions for breast–cancer prevention are associated with adverse side effects that frequently deter women from selecting these evidence-based risk-reducing procedures. In addition, modifiable lifestyle changes can improve breast cancer risk but can be challenging in execution. Therefore, women who are considered high risk due to non-modifiable factors, such as BRCA1/2 mutations or a strong family history of breast cancer, are in need of alternative prevention procedures. Here, we review investigational preclinical and clinical approaches at a systemic and local level that focus on non-modifiable breast cancer risk-reducing interventions. One in eight women will develop breast cancer in the US. For women with moderate (15–20%) to average (12.5%) risk of breast cancer, there are few options available for risk reduction. For high-risk (>20%) women, such as BRCA mutation carriers, primary prevention strategies are limited to evidence-based surgical removal of breasts and/or ovaries and anti-estrogen treatment. Despite their effectiveness in risk reduction, not many high-risk individuals opt for surgical or hormonal interventions due to severe side effects and potentially life-changing outcomes as key deterrents. Thus, better communication about the benefits of existing strategies and the development of new strategies with minimal side effects are needed to offer women adequate risk-reducing interventions. We extensively review and discuss innovative investigational strategies for primary prevention. Most of these investigational strategies are at the pre-clinical stage, but some are already being evaluated in clinical trials and others are expected to lead to first-in-human clinical trials within 5 years. Likely, these strategies would be initially tested in high-risk individuals but may be applicable to lower-risk women, if shown to decrease risk at a similar rate to existing strategies, but with minimal side effects. [ABSTRACT FROM AUTHOR]

Published
2024
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2. Targeted Inhibition of Pancreatic Acinar Cell Calcineurin Is a Novel Strategy to Prevent Post-ERCP Pancreatitis

Author

Farzad Esni, Tanveer A. Javed, Subramaniam Sanker, Tianming Le, Krishna Prasadan, Ping Guo, George K. Gittes, Abrahim I. Orabi, Carlos A. Castro, Li Wen, Sohail Z. Husain, Xiangwei Xiao, David Ricks, Kristy Boggs, and John F. Eisses

Subjects
0301 basic medicine, FK506, education, Phosphatase, MPO, myeloperoxidase, Ela, pancreatic elastase I, medicine.disease_cause, Tm, tdTomato Red reporter, Adeno-Associated Virus, Cyclosporine A, 03 medical and health sciences, AAV, adeno-associated virus, Calcineurin B1, Conditional gene knockout, Acinar cell, Medicine, lcsh:RC799-869, Adeno-associated virus, Pancreatic elastase, Original Research, PEG, polyethylene glycol, Cn, calcineurin, Pancreatic duct, Hepatology, business.industry, Gastroenterology, Intraductal Delivery, medicine.disease, LVNS, low volume normal saline, IL, interleukin, 3. Good health, Calcineurin, CreERT2, Cre recombinase estrogen receptor T2, 030104 developmental biology, medicine.anatomical_structure, PEP, post-ERCP pancreatitis, LSL, Lox-Stop-Lox, Immunology, cardiovascular system, Cancer research, Pancreatitis, lcsh:Diseases of the digestive system. Gastroenterology, business, CsA, cyclosporine A, ERCP, endoscopic retrograde cholangiopancreatography, circulatory and respiratory physiology
Abstract

Background & Aims: There is a pressing need to develop effective preventative therapies for postâendoscopic retrograde cholangiopancreatography pancreatitis (PEP). We showed that early PEP events are induced through the calcium-activated phosphatase calcineurin and that global calcineurin deletion abolishes PEP in mice. A crucial question is whether acinar cell calcineurin controls the initiation of PEP in vivo. Methods: We used a mouse model of PEP and examined the effects of in vivo acinar cell-specific calcineurin deletion by either generating a conditional knockout line or infusing a novel adeno-associated virusâpancreatic elastase improved Cre (IâiCre) into the pancreatic duct of a calcineurin floxed line. Results: We found that PEP is dependent on acinar cell calcineurin in vivo, and this led us to determine that calcineurin inhibitors, infused within the radiocontrast, largely can prevent PEP. Conclusions: These results provide the impetus for launching clinical trials to test the efficacy of intraductal calcineurin inhibitors to prevent PEP. Keywords: Adeno-Associated Virus, Calcineurin B1, FK506, Cyclosporine A, Intraductal Delivery

Published
2017
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3. Optimization of composition and obtainment parameters of biocompatible nanoemulsions intended for intraductal administration of piplartine (piperlongumine) and mammary tissue targeting

Author

Vanessa F.M. Carvalho, Sandra Costa-Fernandez, Edilberto R. Silveira, Giovanna Cassone Salata, Alexandre A. Steiner, Luciana B. Lopes, Gabriel Lima Barros de Araujo, Letícia V. Costa-Lotufo, Marlus Chorilli, Jenyffer Kelly Rocha De Matos, Universidade de São Paulo (USP), Universidade Estadual Paulista (Unesp), and Univ Fed Ceara

Subjects
Glycerol, Swine, Bioadhesive, Sonication, Polysorbates, Pharmaceutical Science, 02 engineering and technology, 030226 pharmacology & pharmacy, Chorioallantoic Membrane, Chitosan, 03 medical and health sciences, chemistry.chemical_compound, Mammary Glands, Animal, Breast cancer, Intraductal delivery, 0302 clinical medicine, Nanoemulsion, Pulmonary surfactant, In vivo, Phosphatidylcholine, Animals, Hyaluronic Acid, Rats, Wistar, Piplartine, Isopropyl myristate, Piperidones, Piperlongumine, Skin, Bioadhesion, Chromatography, QUITOSANA, Drug Administration Routes, Adhesiveness, Dioxolanes, 021001 nanoscience & nanotechnology, Antineoplastic Agents, Phytogenic, chemistry, Phosphatidylcholines, Nanoparticles, Emulsions, Female, 0210 nano-technology, Chickens
Abstract

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

Published
2019

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