Development of safe and easily scalable nanomedicine to deliver highly hydrophobic anti-cancer drug

Omkar Mhatre’s interview with Bio Patrika hosting “Vigyan Patrika”, a series of author interviews. Mhatre completed his B.Tech from the ICT Mumbai and M.Tech from IIT Bombay. He finished M.Tech dissertation work in cancer nanomedicine under the guidance of Prof. Rohit Srivastava. Currently, he is a PhD student in the Department of Biomedical Engineering at the University of Delaware, USA. Here he talks about his first-author research article (M.Tech research work) titled “pH-responsive delivery of anti-metastatic niclosamide using mussel inspired polydopamine nanoparticles” published in the International Journal of Pharmaceutics (2021).

How would you explain your paper’s key results to the non-scientific community?

Our work demonstrated formulation strategy for a repurposed anti-cancer drug, Niclosamide using a biocompatible polymer, polydopamine. The preliminary studies showed the formulation strategy’s success against breast cancer cells where it inhibited cancer cells’ migratory ability and metabolism.

There are plenty of anti-cancer drugs in the market today, but most of them face some common problems such as hydrophobicity, toxicity to normal cells and high price. In recent years, nanotechnology has helped to overcome these challenges. Nanosized drug-encapsulated particles (< 200 nm) help to reduce toxicity and increase bioavailability of hydrophobic drugs. This technology is particularly useful in cancer therapy because blood vessels around a tumor are ‘leaky’, and they allow these particles to exit blood vessels and reach the tumor site. There have been several innovations to improve upon this basic idea of nanoparticle-based drug delivery. While there has been remarkable success in the field, a few limitations still exist. Firstly, the anti-cancer drugs are expensive and developing new drugs requires billions of dollars in investment and anywhere between 5-10 years to reach the patients. Secondly, the use of organic solvents during the manufacturing of nanoparticle formulations carries high energy and environmental costs.

Niclosamide is an FDA approved, relatively cheap drug and hence may not require the same amount of money and time as the new drugs to be translated into the clinic for anti-cancer therapy. Moreover, our synthesis uses FDA approved reagents and limits the use of organic solvent to levels below the recommended safety limits. The synthesis is a one-step process with minimal downstream processing which makes it an attractive prospect for large-scale manufacturing.

Figure 1. Niclosamide loaded polydopamine nanoparticles show promising in vitro efficay against metastatic breast cancer cells and are shown to be safe in mice.

What are the possible consequences of these findings for your research area?

Niclosamide has been extensively researched upon for its anti-cancer potential, but it has limited use in cancer therapy due owing to its highly hydrophobic nature. Our proposed method of formulation helps us fabricate monodisperse polydopamine nanoparticles with high drug loading capacity. The systematic experimental design approach and numerical optimization make this formulation easily reproducible. This method can be adopted by people trying to design a delivery system for other highly hydrophobic drugs.

“Our proposed method of formulation helps us fabricate monodisperse polydopamine nanoparticles with high drug loading capacity.”

What was the exciting moment (eureka moment) during your research?

It was when we got consistent nanoparticle size and morphology for 3 different scaled up batches of synthesis. We were confident of this method working on smaller scale to give consistent size distribution and high drug loading, but we were very happy to see the same results reproduced in larger batches.

What do you hope to do next?

We showed that the polydopamine nanoparticles synthesized by our method are non-toxic to mice. Further studies are required to evaluate in vivo nanoparticle biodistribution, drug release and efficacy in a mouse model of breast cancer.

Where do you seek scientific inspiration?

My inspiration comes from the everyday objects and incidences. I believe science cannot be done staying aloof from the society; it goes along with contemporary beliefs. The best way to sample the world around me is through regular interactions with my friends, peers and advisors, music and long strolls through parks and trails.

How do you intend to help Indian science improve?

I love the tenacity that Indian science has. It helps us to run and sustain a robust innovation ecosystem. However, there is still a little disconnect between how school children are taught science and how science is actually done at the laboratory or industrial level. It becomes difficult for students to transition from schools to university in STEM fields due to this drastic difference in expectations at these two levels. I think, more overlap between academic research and primary education is necessary to bridge this gap. I would like to be a part of creating an environment that motivates people to inculcate scientific temperament from a young age.

Reference

Mhatre O, Reddy BPK, Patnaik C, Chakrabarty S, Ingle A, De A, Srivastava R. pH-responsive delivery of anti-metastatic niclosamide using mussel inspired polydopamine nanoparticles. Int J Pharm. 2021 Feb 1;597:120278. doi: 10.1016/j.ijpharm.2021.120278. Epub ahead of print. PMID: 33540007.

Prof. Rohit Srivastavs lab: https://www.nanobioslab.com/

Edited by: Govinda Raju Yedida (Volunteer, Bio Patrika)

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