Co-delivery of docetaxel and gemcitabine by anacardic acid modified self-assembled albumin nanoparticles for effective breast cancer management

Varun Kushwah, Sameer S. Katiyar, Chander Parkash Dora, Ashish Kumar Agrawal, Dimitrios A. Lamprou, Ramesh C. Gupta, Sanyog Jain*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)
347 Downloads (Pure)

Abstract

In the present study, we have modified bovine serum albumin (BSA) by covalently conjugating with anacardic acid (AA) and gemcitabine (GEM) and further used for development of docetaxel (DTX) loaded nanoparticles (AA-GEM-BSA NPs). AA is supposed to provide tumor targeting through VEGF receptors overexpressed in tumors, while the combination of GEM and DTX is supposed to provide synergistic activity by targeting multiple pathways. The conjugate was synthesized via carbodiimide chemistry and characterized by 1H NMR, FTIR, MALDI-TOF and elemental analysis. Conformational changes owing to conjugation of AA and GEM were estimated via fluorescence, Raman and CD spectroscopy, while changes in physiochemical properties were studied by differential scanning calorimetry (DSC), thermogravimetry (TGA) and contact angle goniometry (CAG). Synthesized conjugate was further transformed into DTX loaded NPs and freeze dried. Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM) demonstrated formation of spherical NPs having particle size, 163 ± 8 nm, PDI, 0.13 ± 0.09 and ZP, −27 ± 1 mV. Cellular uptake in MCF-7 and MDA-MB-231 revealed hNTs, OATP1B3 independent, clathrin mediated internalization followed via nuclear co-localization of C-6 loaded AA-GEM-BSA NPs, responsible for significantly higher apoptosis index. Pharmacokinetic profile of DTX loaded AA-GEM-BSA NPs revealed 6.12 and 3.27-fold and 6.28 and 8.9-fold higher AUC and T1/2 values of DTX and GEM as compared to Taxotere® and Gemzar® respectively. Interestingly, the developed NPs were found safe with no marked effect on RBCs, lower hepato and nephro toxicity. Data in hand suggest promising potential of developed NPs in ameliorating the pharmacokinetic and therapeutic profile of combinatorial regimen of DTX and GEM. 

Original languageEnglish
Pages (from-to)424-436
Number of pages13
JournalActa Biomaterialia
Volume73
Early online date09 Apr 2018
DOIs
Publication statusPublished - Jun 2018
Externally publishedYes

Keywords

  • Biodistribution
  • Combination chemotherapy
  • DMBA breast cancer model
  • Drug-polymer conjugate
  • Self-assembled nanoparticle
  • Targeted drug delivery

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

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