Page 55 - _NIPER-G Annual Report 2019-201

Research Area-5

Polymeric Core–Shell Combinatorial Nanomedicine for Synergistic Anticancer
Therapyv(Collaboration with INST Mohali)
Core−shell nanostructures are promising platforms for combination drug delivery. However,
their complicated synthesis process, poor stability, surface engineering, and low
biocompatibility are major hurdles. Herein, a carboxymethyl chitosan-coated poly(lactide-co-
glycolide) (cmcPLGA) core−shell nanostructure is prepared via a simple one-step
nanoprecipitation self-assembly process. Engineered core−shell nanostructures are tested for
combination delivery of loaded docetaxel and doxorubicin in a cancer-mimicked environment.
The drugs are compartmentalized in a shell (doxorubicin, Dox) and a core (docetaxel, Dtxl)
with loading contents of ∼1.2 and ∼2.06%, respectively. Carboxymethyl chitosan with both
amine and carboxyl groups act as a polyampholyte in diminishing ζ-potential of nanoparticles
from fairly negative (−13 mV) to near neutral (−2 mV) while moving from a physiological pH
(7.4) to an acidic tumor pH (6) that can help the nanoparticles to accumulate and release the
drug on-site. The dual-drug formulation was found to carry a clinically comparable 1.7:1 weight
ratio of Dtxl/Dox, nanoengineered for the sequential release of Dox followed by Dtxl. Single
and engineered combinatorial nanoformulations show better growth inhibition toward three
different cancer cells compared to free drug treatment. Importantly, Dox−Dtxl cmcPLGA
nanoparticles scored synergism with combination index values between 0.2 and 0.3 in BT549
(breast ductal carcinoma), PC3 (prostate cancer), and A549 (lung adenocarcinoma) cell lines,
demonstrating significant cell growth inhibition at lower drug concentrations as compared to
single-drug control groups. The observed promising performance of dual-drug formulation is
due to the G2/M phase arrest and apoptosis.
Shanavas A, Jain NK, Kaur N, Thummuri D, Prasanna M, Prasad R, Naidu VG, Bahadur D,
Srivastava R. Polymeric Core–Shell Combinatorial Nanomedicine for Synergistic Anticancer
Therapy. ACS omega. 2019 Nov 11;4(22):19614-22.

Graphical Abstract

Figure . Schematic illustration showing fabrication of cmcPLGA core−shell nanoparticles
via nanoprecipitation followed by solvent evaporation and electrostatic interaction induced
self-assembly process.

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