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Monitoring of Nanodrug Accumulation in Murine Breast Cancer Metastases
Published on: August 23, 2024
Enhanced noscapine delivery using estrogen-receptor-targeted nanoparticles for breast cancer therapy
Jitender Madan1, Sushma R Gundala, Yoganjaneyulu Kasetti
1aDepartment of Biology, Georgia State University, Atlanta, Georgia, USA bDepartment of Pharmaceutics, Chandigarh College of Pharmacy cDepartment of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Mohali, Punjab dDr. B.R Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India.
Abstract:
Noscapine (Nos), an orally available plant-derived antitussive alkaloid, is in phase II clinical trials for cancer chemotherapy. It has extensively been shown to inhibit tumor growth in nude mice bearing human xenografts of hematopoietic, breast, lung, ovarian, brain, and prostate origin. However, high tumor-suppressive Nos dosages encumber the development of oral controlled-release formulations because of a short biological half-life (<2 h), poor absorption, low aqueous solubility, and extensive first-pass metabolism. Here, we present the design, fabrication, optimization, characterization, and biological evaluation of estrone-conjugated noscapine-loaded gelatin nanoparticles (Nos-ES-GN) for targeting estrogen-receptor-positive breast cancer MCF-7 cells. Gelatin nanoparticles (GN) were a uniformly compact size, stable at physiological pH, and showed a drug entrapment efficiency of 66.1±5.9 and 65.2±5.6% for Nos-GN and Nos-ES-GN, respectively. The secondary structure of gelatin nanocoacervates was predicted using circular dichroism and in-silico molecular modeling. Our data suggest that ethanol-fabricated GN retained the α-helical content of gelatin, whereas acetone favored the formation of random coils. The conjugation of estrone to Nos-GN did not affect the release rate of the drug, and both formulations followed first-order release kinetics with an initial burst, followed by a slow release. The IC50 value of Nos-ES-GN was 21.2 μmol/l, which was ∼50% lower than the free drug (43.3 μmol/l), suggesting targeted drug delivery. Our cell uptake study carried out in an estrogen-receptor-positive (MCF-7) and negative (MDA-MB-231) cancer cell lines showed greater accumulation of Nos-ES-GN in MCF-7 cells instead of MDA-MB-231 cells. Our data indicated that estrone-conjugated nanoparticles may potentially be used for targeting breast cancer cells.
Insights
Estrone-conjugated noscapine nanoparticles show promise for targeted breast cancer therapy. These novel nanoparticles enhance drug delivery and efficacy against estrogen-receptor-positive cancer cells, reducing required dosages.
Area of Science:
- Nanotechnology
- Pharmaceutical Sciences
- Oncology
Background:
- Noscapine, an alkaloid antitussive, exhibits tumor-suppressive properties but faces formulation challenges due to poor pharmacokinetics.
- Developing effective drug delivery systems is crucial for enhancing noscapine's therapeutic potential in cancer chemotherapy.
- Targeting specific cancer cell receptors can improve drug efficacy and reduce systemic toxicity.
Purpose of the Study:
- To design, fabricate, and evaluate estrone-conjugated noscapine-loaded gelatin nanoparticles (Nos-ES-GN) for targeted delivery to estrogen-receptor-positive breast cancer cells.
- To investigate the physicochemical properties, drug release kinetics, and cellular uptake of the developed nanoparticles.
- To assess the in vitro efficacy of Nos-ES-GN compared to free noscapine.
Main Methods:
- Gelatin nanoparticles (GN) loaded with noscapine (Nos-GN) and estrone-conjugated noscapine (Nos-ES-GN) were fabricated and characterized.
- Drug entrapment efficiency, particle size, stability, and secondary structure of gelatin were analyzed.
- In vitro drug release kinetics, IC50 values, and cellular uptake in MCF-7 and MDA-MB-231 cell lines were evaluated.
Main Results:
- Nos-ES-GN exhibited uniform size, stability at physiological pH, and good drug entrapment efficiency.
- Ethanol-based fabrication retained gelatin's α-helical content, influencing nanoparticle structure.
- Nos-ES-GN demonstrated a significantly lower IC50 value and enhanced cellular uptake in estrogen-receptor-positive MCF-7 cells compared to free noscapine.
Conclusions:
- Estrone conjugation to noscapine-loaded gelatin nanoparticles facilitates targeted delivery to estrogen-receptor-positive breast cancer cells.
- Nos-ES-GN show enhanced in vitro efficacy and cellular accumulation, suggesting potential for improved breast cancer treatment.
- This targeted nanoparticle approach may overcome the limitations of conventional noscapine formulations for cancer therapy.
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