Docetaxel loaded immunonanoparticles delivery in EGFR overexpressed breast carcinoma cells

Docetaxel (DTX), one of the most effective chemotherapeutic agents for the treatment of metastatic breast cancer but finds limited clinical applications due to toxicity imparted by surfactant present in marketed formulation and non-specific bio-distribution of the drug. To address these issues, this...

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Bibliographic Details
Published inJournal of drug delivery science and technology Vol. 45; pp. 334 - 345
Main Authors Yewale, Chetan, Baradia, Dipesh, Patil, Sushilkumar, Bhatt, Priyanka, Amrutiya, Jitendra, Gandhi, Ravi, Kore, Girish, Misra, Ambikanandan
Format Journal Article
LanguageEnglish
Published Elsevier B.V 01.06.2018
Subjects
Albumin
Cell proliferation
Chemotherapy
Drug delivery
scFv
Targeted nanoparticle
Cell proliferation
Albumin
Chemotherapy
Drug delivery
Targeted nanoparticle
scFv
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Summary:Docetaxel (DTX), one of the most effective chemotherapeutic agents for the treatment of metastatic breast cancer but finds limited clinical applications due to toxicity imparted by surfactant present in marketed formulation and non-specific bio-distribution of the drug. To address these issues, this study was undertaken by taking a novel approach of fabrication of DTX loaded scFv (Single chain variable fragment) conjugated human serum albumin (HSA) immunonanoparticles (INPs). Developed INPs were characterized for particle size, zeta potential, entrapment efficiency, in vitro drug release, stability, in vitro cell line studies and in vivo animal studies. DTX-HSA-INPs were spherical in shape with mean diameter of 160.7 ± 5.5 nm and they showed specific binding to the targeted receptor when studied in vitro in cell line culture. It showed enhanced intracellular accumulation of INPs in EGFR expressing breast carcinoma cells as compared to EGFR negative breast carcinoma cells and non-targeted nanoparticles (NPs) Improved cytotoxic potential was demonstrated by DTX-HSA-INPs compared to marketed formulation in EGFR-expressing breast carcinoma cells (MDA-MB-468 and MDA-MB-231). Improved pharmacokinetic profile and long circulation in vivo in animals also revealed that the novel scFv targeted DTX-HSA-INPs can be a better and one of the promising alternatives for breast cancer therapy. [Display omitted]
ISSN:1773-2247
DOI:10.1016/j.jddst.2018.03.027