Chemopreventive efficacy of curcumin-loaded PLGA microparticles in a transgenic mouse model of HER-2-positive breast cancer
| Autor: | Komal Shahani, Brenda Koniar, Alex E. Grill, Jayanth Panyam |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Vascular Endothelial Growth Factor A Curcumin Pharmaceutical Science Breast Neoplasms Mice Transgenic Pharmacology medicine.disease_cause Article 03 medical and health sciences chemistry.chemical_compound Polylactic Acid-Polyglycolic Acid Copolymer In vivo medicine Animals Anticarcinogenic Agents Lactic Acid Microparticle Cell Proliferation Drug Carriers Mice Inbred BALB C Neovascularization Pathologic Chemistry NF-kappa B Genes erbB-2 Bioavailability PLGA Disease Models Animal 030104 developmental biology Delayed-Action Preparations Cytokines Female Carcinogenesis Drug carrier Polyglycolic Acid |
| Zdroj: | Drug delivery and translational research. 8(2) |
| ISSN: | 2190-3948 |
| Popis: | Curcumin has shown promising inhibitory activity against HER-2 positive tumor cells in vitro but suffers from poor oral bioavailability in vivo. Our lab has previously developed a polymeric microparticle formulation for sustained delivery of curcumin for chemoprevention. The goal of this study was to examine the anticancer efficacy of curcumin loaded polymeric microparticles in a transgenic mouse model of HER-2 cancer, Balb-neuT. Microparticles were injected monthly, and mice were examined for tumor appearance and growth. Initiating curcumin microparticle treatment at 2 or 4 weeks of age delayed tumor appearance by 2–3 weeks compared to that in control mice that received empty microparticles. At twelve weeks, abnormal (lobular hyperplasia, carcinoma in situ, and invasive carcinoma) mammary tissue area was significantly decreased in curcumin microparticle-treated mice, as was CD-31 staining. Curcumin treatment decreased mammary VEGF levels significantly, which likely contributed to slower tumor formation. When compared to saline controls, however, blank microparticles accelerated tumorigenesis and curcumin treatment abrogated this effect, suggesting that PLGA microparticles enhance tumorigenesis in this model. PLGA microparticle administration was shown to be associated with higher plasma lactic acid levels and increased activation of NF-κB. The unexpected side effects of PLGA microparticles may be related to the high dose of the microparticles that was needed to achieve sustained curcumin levels in vivo. Approaches that can decrease the overall dose of curcumin (for example, by increasing its potency or reducing its clearance rate) may allow the development of sustained release curcumin dosage forms as a practical approach to cancer chemoprevention. |
| Databáze: | OpenAIRE |
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