Chemopreventive efficacy of curcumin-loaded PLGA microparticles in a transgenic mouse model of HER-2-positive breast cancer

Alexander E Grill, Komal Shahani, Brenda Koniar, Jayanth Panyam

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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 12 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-κΒ. 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.

Original languageEnglish (US)
Pages (from-to)329-341
Number of pages13
JournalDrug Delivery and Translational Research
Volume8
Issue number2
DOIs
StatePublished - Apr 1 2018

Fingerprint

Curcumin
Transgenic Mice
Breast Neoplasms
Neoplasms
Chemoprevention
Carcinogenesis
Breast
polylactic acid-polyglycolic acid copolymer
Dosage Forms
Vascular Endothelial Growth Factor A
Biological Availability
Hyperplasia
Lactic Acid
Therapeutics
Staining and Labeling
Carcinoma

Keywords

  • Cancer chemoprevention
  • Inflammation
  • Polymeric microparticles
  • Sustained release
  • Tumorigenesis

PubMed: MeSH publication types

  • Journal Article

Cite this

Chemopreventive efficacy of curcumin-loaded PLGA microparticles in a transgenic mouse model of HER-2-positive breast cancer. / Grill, Alexander E; Shahani, Komal; Koniar, Brenda; Panyam, Jayanth.

In: Drug Delivery and Translational Research, Vol. 8, No. 2, 01.04.2018, p. 329-341.

Research output: Contribution to journalArticle

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