Asifkhan Shanavas: Habitat Centre, Institute of Nano Science and Technology, Phase-X, Sector-64, Mohali, Punjab 160062, India.
Nishant K Jain: Department of Biosciences and Bioengineering and Department of Metallurgical Engineering & Materials Science, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
Navneet Kaur: Habitat Centre, Institute of Nano Science and Technology, Phase-X, Sector-64, Mohali, Punjab 160062, India.
Dinesh Thummuri: National Institute of Pharmaceutical Education and Research Guwahati, Nits Mirza Road, Parlli Part, Guwahati Assam 781125, India.
Maruthi Prasanna: Department of Biosciences and Bioengineering and Department of Metallurgical Engineering & Materials Science, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
Rajendra Prasad: Department of Biosciences and Bioengineering and Department of Metallurgical Engineering & Materials Science, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
Vegi Ganga Modi Naidu: National Institute of Pharmaceutical Education and Research Guwahati, Nits Mirza Road, Parlli Part, Guwahati Assam 781125, India.
Dhirendra Bahadur: Department of Biosciences and Bioengineering and Department of Metallurgical Engineering & Materials Science, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
Rohit Srivastava: Department of Biosciences and Bioengineering and Department of Metallurgical Engineering & Materials Science, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
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--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.
