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Cytotoxic Activity and Anti-Migratory Effect of Berberine-Phytantriol Liquid Crystalline on Non-Small-Cell Lung Cancer

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Kamal Dua aimed to formulate an optimized formulation of berberine-phytantriol-loaded liquid crystalline nanoparticles (BP-LCNs) and to investigate the in vitro anti-cancer activity in a human lung adenocarcinoma A549 cell line.

Image courtesy of interviewee. June 5, 2024

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This video is a detailed presentation regarding research conducted by a team at the Graduate School of Health and Discipline of Pharmacy at the University of Technology Sydney. The research primarily focuses on lung diseases, particularly lung cancer, asthma, and COPD (chronic obstructive pulmonary disease).

In the study, the team investigates phytol-loaded liquid crystalline nanoparticles containing berberine, a natural compound known for its various therapeutic effects, including use in treating diabetes and high cholesterol. They emphasize berberine’s efficacy against non-small cell lung cancer, a prevalent type of lung cancer accounting for about 85% of cases.

The research highlights the issue of berberine's low water solubility, which hinders its absorption and efficacy. The study’s novel approach uses nanoparticles to improve the solubility and delivery of berberine, enhancing its therapeutic potential while reducing side effects and required dosages.

The study demonstrates that the berberine-loaded nanoparticles effectively inhibit cancer cell proliferation, migration, and colony formation in vitro. Key proteins and genes associated with lung cancer pathogenesis were positively impacted by the treatment.

The research is collaborative, integrating various scientific fields and includes a wider vision for animal and potentially human trials in the future. The team is also working on developing dry powder inhalers for delivering these nanoparticles directly to the lungs.

In summary, this study showcases the promising potential of berberine-loaded nanoparticles as a therapeutic option for treating lung cancer, while also addressing challenges related to drug delivery and bioavailability.

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Here are some articles that may be similar to the video, as they also focus on lung diseases, nanoparticles, and the therapeutic potential of natural compounds in cancer treatment:

1. **Nanoparticle-based Drug Delivery Systems in Lung Cancer**:
This article reviews various nanoparticle technologies developed for the targeted delivery of chemotherapeutic agents specifically for lung cancer treatment, discussing their mechanisms of action and potential benefits in overcoming barriers to drug delivery.

2. **The Role of Berberine in Cancer Prevention and Treatment**:
This study explores the effects of berberine on various cancer types, with a focus on its mechanisms of action, clinical implications, and synergy with other therapies in treating respiratory diseases, including lung cancer.

3. **Advancements in Nanotechnology for Asthma Therapy**:
This article discusses the application of nanotechnology in improving drug delivery systems for asthma treatment, focusing on the formulation of inhalable nanoparticles that enhance drug solubility and bioavailability.

4. **Phytochemicals in the Treatment of Chronic Obstructive Pulmonary Disease**:
This research investigates the therapeutic roles of various phytochemicals, including berberine, in the management of COPD, highlighting their anti-inflammatory and antioxidant properties.

5. **Targeted Nanoparticles for Lung Cancer Therapy**:
This paper presents recent findings on the development of targeted nanoparticles designed to deliver therapeutics directly to lung cancer cells, enhancing drug efficacy while minimizing side effects.

6. **Clinical Applications of Phytol in Respiratory Disorders**:
This review article discusses the potential clinical applications of phytol and its derivatives in treating respiratory conditions, including details about delivery systems and therapeutic effectiveness.

7. **Emerging Therapeutics in Non-Small Cell Lung Cancer**:
This review covers novel treatment approaches for non-small cell lung cancer, including the use of natural compounds and nanoparticles, emphasizing their mechanisms and clinical relevance.

8. **Utilization of Liquid Crystalline Nanoparticles in Drug Delivery**:
This article explores the use of liquid crystalline nanoparticles for drug delivery across various therapeutic areas, including respiratory diseases, detailing their advantages in enhancing solubility and therapeutic action.

These articles emphasize similar themes and topics to the research you , focusing on lung diseases, the role of nanoparticles in drug delivery, and the use of natural compounds in cancer therapeutics.

X-TIMESTAMP-MAP:LOCAL=00:00:00.000,MPEGTS=900000

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I in terms of my laboratory,

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I'm based at the Graduate School of Health

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and Discipline of Pharmacy at University

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of Technology Sydney, where my research team primarily focus

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on various lung diseases

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with the main emphasis on lung cancer, asthma, and COPD.

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Now, in today's study, we are going to talk more about

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and discuss about the phytol, loaded,

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liquid crystalline nanoparticles containing berberine.

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So we have understand,

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and we have studied the efficacy

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of these nanoparticles in lung cancer.

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Lung cancer is actually highly prevalent cancer,

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and with over more than 2 million new cases in the

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worldwide, it reported in just 2020

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and it's been rising every year.

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Now, this lung cancer is one of the major cause

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of the deaths globally,

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and if we look at the statistics, there are

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around 1.79 million reported deaths, which contributes

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to almost 18% of the total cancer deaths

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around the globe in 2020.

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Now, there are two types of the lung cancer.

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One is called as a small cell lung cancer, other is called

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as a non-small cell lung cancer.

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Our studies emphasized

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and focused on the non-small cell lung cancer.

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This why we have studied on non-small cell lung cancer

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because this is a cancer which actually makes up to 85%

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of the lung cancer cases,

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and it is, it still remains a major most common

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cause of the lung cancer.

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Among the both, the only difference between both of these is

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that the small cell lung cancer is still an aggressive one,

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but the nonsmall cell lung cancer,

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because of its high prevalence,

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we have undertook this study.

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The, the small cell lung cancer.

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In, in, in that cancer, it's a metastasis is more

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as compared to the non-small cell cancer,

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which mostly happened in the lymph nodes.

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In our study we have, we undertook a study on a natural

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compound because around the globe people are getting very

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much aware nowadays about the alternative

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and complementary medicine.

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Everyone think and takes one

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or the other form of the natural compound in their diet or

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or to treat any of their elements.

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The best example, which I usually give in every talk is when

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someone really want to even lose a weight,

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they go on their diet with salad.

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And that salad actually is itself is nothing,

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but it's a kind of, plant-based products,

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which you are eating and

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to cut your certain metabolism into the body.

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In a same way, the pharmaceuticals are having an abundant

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therapeutic potential.

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In this study, we have used berberine.

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Berberine actually, in scientific terms is an

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isoc and alkaloid.

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It is actually also been available in the market in terms

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of the chemical compounds called as berberine hydrochloride.

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It's already been used in ancient history

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and for long ago by Chinese

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and also in the Ayurvedic medicine

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to treat various elements like diabetes, high cholesterol,

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high blood pressure, and various other conditions.

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But it was not explored on lung cancer.

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And this is how our study came into the picture,

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and we were the first one who demonstrated

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that it is quite effective in the small

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non-small cell lung cancer.

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Now, this article has been really got a very

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high alt metric.

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It has already been posted by, across the globe

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by multiple news channels.

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And so what we have seen here is that all these berberine,

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which is been used,

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they can treat several metabolic health

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condition, as I mentioned.

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But there is a problem with this perine.

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The burberine itself is a very water insoluble and

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because of its poorly water-soluble nature,

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its absorption in the body is very low,

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and that can even cause toxicity if being given

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at a higher doses.

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So because its absorption is low,

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and in scientific term, we usually call it

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as an bioavailability.

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So the bioavailability of this drug is very, very low

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because it's poorly water-soluble.

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So what we have used in our studies, we have used a very

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advanced novel concept of nanoparticles.

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Nanoparticles are nothing, but they are very tiny balls.

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The best example I can give is like a tennis ball,

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and it is hollow from inside

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and you fill your drug in the middle, in the hollow part

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of the tennis ball, the outer part

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of the tennis ball is a polymer sheath.

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In our case, we have used python roll is a polymer.

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So when it's been gone in and and

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and been taken up by the organ

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or the tissue, which is lung hair, it retains on the surface

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and it slowly dissolved the polymer

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and the drug release for a longer duration of time.

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So it means the patient don't have to take multiple dose,

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the patient have a better compliance,

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and it also reduces the side effect.

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The best example and the best application

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and useful nature

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of these nanoparticle is it helps even also improving the

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solubility of berberine.

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So when berberine is already poorly water soluble

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and we prepare in form of a nanoparticles,

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it releases the drug for a longer duration of time.

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That's the whole idea

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and the concept we have used in our study.

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That's a very good question actually.

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It's, this is a question which is, this is

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what we have actually probed

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and elucidated in our study how exactly it had worked out.

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So what we have done, as I mentioned, that

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it has been incorporated into a liquid crystalline

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nanoparticles and those nanoparticles,

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we are still been trying to get it into a dry powder inhaler

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so that when patient can have a puff, it can go directly on

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and deposit on the epithelial cells and release the drug.

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Now, before, actually I can tell you more in terms of the,

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how the mechanism has happened.

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It is really important to know

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what is the methodology we have used in the study.

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Now, in this study we have,

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we have done all the in vitro studies.

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It means we have worked

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and tested our nanoparticles on the lung cancer cells,

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which is a 5 49.

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Um, in vitro the major parameters,

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what we have studied in our study,

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they include proliferation.

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Proliferation is one

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of the major mechanism in the cancer study,

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which involves the rapid growth

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or reproduction of the cells.

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It means quite a number of the cells they quickly grow.

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So we have studied proliferation

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and growing of the cancerous cell is not good.

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The second thing, what we have studied is migration.

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So your cells can easily move from one part to another part

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and the tumor mass can detach

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and it can form a multicellular group.

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It can penetrate into the surrounding tissues, you know, so,

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so the second thing, what we have studied is migration.

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We have also studied various other exa

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ex experiments like cell migration, cell, cell count,

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and and finally we have identified various proteins

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and genes which are actually causing

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the pathogenesis of lung cancer.

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But when we have actually treated

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with our berberine nanoparticles,

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they reduces all those proteins

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and genes which are responsible for the cancer.

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Now let me tell you how exactly

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and what proteins we have been involved with.

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Now, first of all, we have prepared those nanoparticles

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and those nanoparticles were being optimally characterized

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because we cannot just give the nanoparticles as we design.

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We have to make sure that they are having a proper

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optimized favorable particle size.

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So enough drug has been encapsulated in the nanoparticles

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and it also has a good drug release

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for a longer duration of time.

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So we have first of all, prepared the nanoparticles

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and characterized for their

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physical chemical characterization.

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After that, we treated those nanoparticles.

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Once they are optimized with the A 5 49 cells,

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which are the lung cancer cells, when we have treated those,

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we measured the mRNA level, which is the qPCR r

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what we run the mRNA level of various tumor

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associated genes.

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And the various tumor associated genes we have looked at in

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in it involves P 10, P 53, and KRT 18.

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Now these are the protein expressions.

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They, we have measured even with the,

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human oncology protein array

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and we have clearly seen that when the cells are treated

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with the nanoparticles containing berberine,

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the liquid crystalline nanoparticles, they actually reduces

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or they decrease the proliferation, which I said

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that the cell growth, the migration

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of those cancerous cells,

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and even the colon colony forming of those cancerous cells

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of a 5 49 in a dose dependent manner where

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what we have observed it actually upregulate the two

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particular mRNA level.

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One is the P 10 and P 53,

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and it also downregulate in terms of the genes KRT 18,

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which is so, so the downregulation of KRT 18

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and the upregulation of P 10 and P 53 is good

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because that can help actually reduces the

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pathogenesis of the drug.

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And when we looked actually at the protein expression,

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we have looked at various number of proteins in,

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and those proteins were directly related

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with the various mechanism and the processes.

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We have looked in cancer

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and that involves proliferation, that involve metastasis

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or what we call as a migration.

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Now, in terms of the proteins, what we have looked

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through the human oncology protein ra, that includes A XL

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CA nine, her one, two, up to three, her one,

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her two, and HER three P-R-G-N-P dgf, aa,

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dkk one cts, P-B-C-L-X, CSF one

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and CAPG.

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Now they, these all proteins,

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what happen when someone have cancer, they usually go up.

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They are very, up-regulated,

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but when we are treating with the berberine nanoparticles,

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they actually reduce what we have shown and which is good.

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So all these proteins, what have been saying,

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they are involved with the proliferation and metastasis.

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Once you treat with the Burberry nanoparticles,

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they get downregulated.

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And once they all are downregulated,

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it means it reduces the pathogenesis of the drug.

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And so we have clearly seen on a gene level,

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at the gene level, as I mentioned,

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we have seen the upregulation of P 10 and P 53.

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And also in terms of the proteins, the numerous proteins,

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which I have mentioned just now, they all are downregulated

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with the treatment of bine loaded,

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liquid nano crystalline nanoparticles.

11:00.565 --> 11:01.785
So overall in this study,

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we have prepared these novel nanoparticles.

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We have not prepared the journalized nanoparticles,

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which various researchers they normally do across

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the globe using the polymeric nanoparticles.

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We have done an another high level

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of the nanoparticles called

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as a liquid crystalline nanoparticles.

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Now this nanoparticles we have prepared,

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we have characterized,

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and we have also actually done all the in vitro studies in

11:28.585 --> 11:30.705
terms of the genes and proteins, which I mentioned.

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This study was a quite a collaborative study

11:33.765 --> 11:35.425
and it'd been done across different

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geographical location across the globe.

11:37.365 --> 11:40.865
The the researchers on this study was from uk,

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from Australia, from Saudi Arabia,

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from India, and from Malaysia.

11:46.515 --> 11:49.415
Uh, it was quite an inter interdisciplinary study

11:49.485 --> 11:52.575
because that involves not only just the one area

11:52.635 --> 11:55.405
of a drug delivery and making the new nanoparticles,

11:55.865 --> 11:57.645
it was the study which was actually

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involving the drug delivery.

12:00.025 --> 12:03.325
It was a study which was also involving the pharmacology

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and as well as the area of immunology.

12:06.585 --> 12:09.685
Now all these three interdisciplinary area are sitting in

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this, and the different researchers in this different

12:12.675 --> 12:14.445
expertise were involved in that,

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where I was the primary lead in this study.

12:17.895 --> 12:21.235
Now, so this is the whole layout of the study

12:21.375 --> 12:24.315
and also the methodology, what we have used in our study

12:25.175 --> 12:27.875
and how burberine actually have shown the,

12:27.875 --> 12:30.395
therapeutic effectiveness in treating the small

12:30.505 --> 12:31.835
non-small cell lung cancer.

12:32.175 --> 12:34.955
The major difference, what we have clearly seen in our study

12:35.055 --> 12:37.155
is the, there, there are a lot of previous study.

12:37.155 --> 12:41.195
There's, I think when people have not really dig into

12:41.195 --> 12:43.035
the lung cancer too much using burberine,

12:43.035 --> 12:44.715
there was only one study, but in

12:44.715 --> 12:48.715
that study they have used burberine up to 90 micromolar.

12:49.135 --> 12:51.795
And when they have used that, such a high concentration

12:51.795 --> 12:54.435
and they have also used it for 24 hours incubation period.

12:55.655 --> 12:58.595
But the findings of our study has established a greater pot

12:58.595 --> 13:01.075
potential of berberine, and we have clearly shown

13:01.075 --> 13:03.595
that the loading of the berberine in a fight,

13:03.865 --> 13:07.115
roil based liquid crystaline nanoparticle formulation, they

13:07.715 --> 13:11.835
actually significantly inhibit the cell proliferation,

13:12.335 --> 13:16.715
the migration and the colony formation in a 5 49 cells up

13:16.715 --> 13:19.195
to the five micromolar burberine concentration.

13:19.215 --> 13:21.115
So it means the patients don't have to go

13:21.415 --> 13:24.475
for a very high dose, they can even go with a smaller dose,

13:24.855 --> 13:27.355
and burberine is commonly available in the,

13:28.025 --> 13:31.285
around the globe on the most of these cist shelves

13:31.425 --> 13:32.645
as a nutraceuticals.

13:33.105 --> 13:35.085
But it's, it's much advisable.

13:35.085 --> 13:36.285
People do take it as a

13:36.285 --> 13:37.885
nutraceuticals in their daily routine.

13:37.995 --> 13:41.325
However, it is always advisable if any, any patient

13:41.545 --> 13:43.005
or any person have a lung cancer.

13:43.065 --> 13:47.045
It is good to have a, consultancy first

13:47.155 --> 13:50.845
with the clinician so that it should not lead to any kind

13:50.845 --> 13:53.725
of the adverse and side effects despite it a nutraceutical.

13:54.425 --> 13:57.485
And, and that's why, the ENT role based nano

13:58.045 --> 14:00.085
delivery system containing burberine in one

14:00.085 --> 14:03.285
of the promising candidate, to treat the lung cancer.

14:03.555 --> 14:05.645
This is what is what we have shown in our study.

14:05.905 --> 14:09.485
But in our study, what we have clearly shown it is showing a

14:09.485 --> 14:10.805
significant inhibition

14:10.985 --> 14:14.445
of a 5 49 cell proliferation migration

14:14.505 --> 14:18.165
and colon colon formation at even just the five micromolar

14:18.165 --> 14:19.805
of the burberine concentration.

14:20.505 --> 14:24.925
So in nutshell, I can say that the, our berberine,

14:24.925 --> 14:28.005
liquid crystalline nanoparticles formulations,

14:28.235 --> 14:31.565
they can potentially actually address the low solubility,

14:32.265 --> 14:35.845
the low oral bio viability, the low efficacy,

14:35.865 --> 14:37.805
and the adverse side effects of burberine.

14:38.465 --> 14:41.925
The PHY is one of a very good polymer that has been used

14:41.945 --> 14:43.645
for the novel drug delivery system

14:43.905 --> 14:45.365
to incorporate the berberine,

14:45.465 --> 14:48.885
and it's a promising delivery candidate, to treat the,

14:49.065 --> 14:50.405
lung cancer in future.

14:51.065 --> 14:52.925
At this stage, we have,

14:53.225 --> 14:56.485
we are successful in developing these, beautiful

14:57.105 --> 14:59.885
eff efficacious, nanoparticles

15:00.265 --> 15:03.565
and we have only tested so far on the in vitro models.

15:04.225 --> 15:07.205
We have also extended our study in the cigarette smoke

15:07.205 --> 15:09.765
induced chronic obstructive pulmonary disease,

15:09.975 --> 15:11.765
which is also called emphysema.

15:12.065 --> 15:14.325
And one of our, that study also is published

15:14.345 --> 15:15.925
and we have also shown, shown

15:15.925 --> 15:18.485
that these nanoparticles are also effective in

15:18.645 --> 15:19.885
treating COPD as well.

15:20.385 --> 15:24.005
Uh, alongside it means reducing the symptoms of the COPD

15:24.185 --> 15:25.245
as well as in lung cancer.

15:26.145 --> 15:28.285
But both of these studies are only been done

15:28.345 --> 15:29.445
at an in vitro level.

15:30.065 --> 15:31.445
At this stage in our lab,

15:31.505 --> 15:33.405
we are currently been moving forward

15:33.505 --> 15:36.365
to do these studies in the animal models of the lung cancer

15:36.545 --> 15:40.565
and COPD and then moving from that, it would be really nice

15:40.565 --> 15:43.285
to see if they show really a quite an efficacious

15:43.285 --> 15:45.485
therapeutic effectiveness in in vivo models,

15:45.875 --> 15:48.085
then it can be taken to the human trials.

15:48.785 --> 15:52.005
So, and finally, alongside at this point of time, we are,

15:52.005 --> 15:53.925
what we are also doing is we are also trying

15:53.925 --> 15:55.725
to encapsulate these, sorry.

15:55.825 --> 15:58.725
We are also trying to actually embed these nanoparticles

15:59.035 --> 16:01.405
into the leak, into the dry powder inhalers.

16:01.745 --> 16:04.285
And we are very closely working with one of the company,

16:04.285 --> 16:07.925
which is the respiratory, specific company,

16:07.985 --> 16:10.805
and they're helping us actually translating our developed

16:10.805 --> 16:13.605
nanoparticles testing into the simulated human models

16:13.745 --> 16:16.045
to see the deposition in the lungs

16:16.215 --> 16:19.005
where exactly those nanoparticles are sitting, so

16:19.005 --> 16:21.805
that an optimal design of the delivery system can be made

16:22.025 --> 16:25.605
and can be used further drown down the translational path.

00:00 - I in terms of my laboratory, I'm based at the Graduate School of Health and Discipline of Pharmacy at University of Technology Sydney, where my research team primarily focus on various lung diseases with the main emphasis on lung cancer, asthma, and COPD.

00:16 - Now, in today's study, we are going to talk more about and discuss about the phytol, loaded, liquid crystalline nanoparticles containing berberine. So we have understand, and we have studied the efficacy of these nanoparticles in lung cancer. Lung cancer is actually highly prevalent cancer, and with over more than 2 million new cases in the worldwide, it reported in just 2020 and it's been rising every year.

00:43 - Now, this lung cancer is one of the major cause of the deaths globally, and if we look at the statistics, there are around 1.79 million reported deaths, which contributes to almost 18% of the total cancer deaths around the globe in 2020. Now, there are two types of the lung cancer. One is called as a small cell lung cancer, other is called as a non-small cell lung cancer. Our studies emphasized

01:08 - and focused on the non-small cell lung cancer. This why we have studied on non-small cell lung cancer because this is a cancer which actually makes up to 85% of the lung cancer cases, and it is, it still remains a major most common cause of the lung cancer. Among the both, the only difference between both of these is that the small cell lung cancer is still an aggressive one, but the nonsmall cell lung cancer, because of its high prevalence,

01:36 - we have undertook this study. The, the small cell lung cancer. In, in, in that cancer, it's a metastasis is more as compared to the non-small cell cancer, which mostly happened in the lymph nodes. In our study we have, we undertook a study on a natural compound because around the globe people are getting very much aware nowadays about the alternative and complementary medicine. Everyone think and takes one

02:02 - or the other form of the natural compound in their diet or or to treat any of their elements. The best example, which I usually give in every talk is when someone really want to even lose a weight, they go on their diet with salad. And that salad actually is itself is nothing, but it's a kind of, plant-based products, which you are eating and to cut your certain metabolism into the body. In a same way, the pharmaceuticals are having an abundant

02:31 - therapeutic potential. In this study, we have used berberine. Berberine actually, in scientific terms is an isoc and alkaloid. It is actually also been available in the market in terms of the chemical compounds called as berberine hydrochloride. It's already been used in ancient history and for long ago by Chinese and also in the Ayurvedic medicine to treat various elements like diabetes, high cholesterol,

03:03 - high blood pressure, and various other conditions. But it was not explored on lung cancer. And this is how our study came into the picture, and we were the first one who demonstrated that it is quite effective in the small non-small cell lung cancer. Now, this article has been really got a very high alt metric. It has already been posted by, across the globe by multiple news channels.

03:28 - And so what we have seen here is that all these berberine, which is been used, they can treat several metabolic health condition, as I mentioned. But there is a problem with this perine. The burberine itself is a very water insoluble and because of its poorly water-soluble nature, its absorption in the body is very low, and that can even cause toxicity if being given at a higher doses.

03:56 - So because its absorption is low, and in scientific term, we usually call it as an bioavailability. So the bioavailability of this drug is very, very low because it's poorly water-soluble. So what we have used in our studies, we have used a very advanced novel concept of nanoparticles. Nanoparticles are nothing, but they are very tiny balls. The best example I can give is like a tennis ball, and it is hollow from inside

04:21 - and you fill your drug in the middle, in the hollow part of the tennis ball, the outer part of the tennis ball is a polymer sheath. In our case, we have used python roll is a polymer. So when it's been gone in and and and been taken up by the organ or the tissue, which is lung hair, it retains on the surface and it slowly dissolved the polymer and the drug release for a longer duration of time. So it means the patient don't have to take multiple dose,

04:50 - the patient have a better compliance, and it also reduces the side effect. The best example and the best application and useful nature of these nanoparticle is it helps even also improving the solubility of berberine. So when berberine is already poorly water soluble and we prepare in form of a nanoparticles, it releases the drug for a longer duration of time. That's the whole idea

05:15 - and the concept we have used in our study. That's a very good question actually. It's, this is a question which is, this is what we have actually probed and elucidated in our study how exactly it had worked out. So what we have done, as I mentioned, that it has been incorporated into a liquid crystalline nanoparticles and those nanoparticles, we are still been trying to get it into a dry powder inhaler so that when patient can have a puff, it can go directly on

05:45 - and deposit on the epithelial cells and release the drug. Now, before, actually I can tell you more in terms of the, how the mechanism has happened. It is really important to know what is the methodology we have used in the study. Now, in this study we have, we have done all the in vitro studies. It means we have worked and tested our nanoparticles on the lung cancer cells, which is a 5 49.

06:13 - in vitro the major parameters, what we have studied in our study, they include proliferation. Proliferation is one of the major mechanism in the cancer study, which involves the rapid growth or reproduction of the cells. It means quite a number of the cells they quickly grow. So we have studied proliferation and growing of the cancerous cell is not good.

06:38 - The second thing, what we have studied is migration. So your cells can easily move from one part to another part and the tumor mass can detach and it can form a multicellular group. It can penetrate into the surrounding tissues, you know, so, so the second thing, what we have studied is migration. We have also studied various other exa ex experiments like cell migration, cell, cell count, and and finally we have identified various proteins and genes which are actually causing

07:11 - the pathogenesis of lung cancer. But when we have actually treated with our berberine nanoparticles, they reduces all those proteins and genes which are responsible for the cancer. Now let me tell you how exactly and what proteins we have been involved with. Now, first of all, we have prepared those nanoparticles and those nanoparticles were being optimally characterized because we cannot just give the nanoparticles as we design.

07:37 - We have to make sure that they are having a proper optimized favorable particle size. So enough drug has been encapsulated in the nanoparticles and it also has a good drug release for a longer duration of time. So we have first of all, prepared the nanoparticles and characterized for their physical chemical characterization. After that, we treated those nanoparticles. Once they are optimized with the A 5 49 cells,

08:04 - which are the lung cancer cells, when we have treated those, we measured the mRNA level, which is the qPCR r what we run the mRNA level of various tumor associated genes. And the various tumor associated genes we have looked at in in it involves P 10, P 53, and KRT 18. Now these are the protein expressions. They, we have measured even with the, human oncology protein array and we have clearly seen that when the cells are treated

08:37 - with the nanoparticles containing berberine, the liquid crystalline nanoparticles, they actually reduces or they decrease the proliferation, which I said that the cell growth, the migration of those cancerous cells, and even the colon colony forming of those cancerous cells of a 5 49 in a dose dependent manner where what we have observed it actually upregulate the two particular mRNA level. One is the P 10 and P 53,

09:08 - and it also downregulate in terms of the genes KRT 18, which is so, so the downregulation of KRT 18 and the upregulation of P 10 and P 53 is good because that can help actually reduces the pathogenesis of the drug. And when we looked actually at the protein expression, we have looked at various number of proteins in, and those proteins were directly related with the various mechanism and the processes. We have looked in cancer

09:39 - and that involves proliferation, that involve metastasis or what we call as a migration. Now, in terms of the proteins, what we have looked through the human oncology protein ra, that includes A XL CA nine, her one, two, up to three, her one, her two, and HER three P-R-G-N-P dgf, aa, dkk one cts, P-B-C-L-X, CSF one and CAPG. Now they, these all proteins, what happen when someone have cancer, they usually go up.

10:16 - They are very, up-regulated, but when we are treating with the berberine nanoparticles, they actually reduce what we have shown and which is good. So all these proteins, what have been saying, they are involved with the proliferation and metastasis. Once you treat with the Burberry nanoparticles, they get downregulated. And once they all are downregulated, it means it reduces the pathogenesis of the drug. And so we have clearly seen on a gene level,

10:43 - at the gene level, as I mentioned, we have seen the upregulation of P 10 and P 53. And also in terms of the proteins, the numerous proteins, which I have mentioned just now, they all are downregulated with the treatment of bine loaded, liquid nano crystalline nanoparticles. So overall in this study, we have prepared these novel nanoparticles. We have not prepared the journalized nanoparticles, which various researchers they normally do across

11:10 - the globe using the polymeric nanoparticles. We have done an another high level of the nanoparticles called as a liquid crystalline nanoparticles. Now this nanoparticles we have prepared, we have characterized, and we have also actually done all the in vitro studies in terms of the genes and proteins, which I mentioned. This study was a quite a collaborative study and it'd been done across different

11:35 - geographical location across the globe. The the researchers on this study was from uk, from Australia, from Saudi Arabia, from India, and from Malaysia. it was quite an inter interdisciplinary study because that involves not only just the one area of a drug delivery and making the new nanoparticles, it was the study which was actually involving the drug delivery. It was a study which was also involving the pharmacology

12:03 - and as well as the area of immunology. Now all these three interdisciplinary area are sitting in this, and the different researchers in this different expertise were involved in that, where I was the primary lead in this study. Now, so this is the whole layout of the study and also the methodology, what we have used in our study and how burberine actually have shown the, therapeutic effectiveness in treating the small non-small cell lung cancer.

12:32 - The major difference, what we have clearly seen in our study is the, there, there are a lot of previous study. There's, I think when people have not really dig into the lung cancer too much using burberine, there was only one study, but in that study they have used burberine up to 90 micromolar. And when they have used that, such a high concentration and they have also used it for 24 hours incubation period. But the findings of our study has established a greater pot potential of berberine, and we have clearly shown

13:01 - that the loading of the berberine in a fight, roil based liquid crystaline nanoparticle formulation, they actually significantly inhibit the cell proliferation, the migration and the colony formation in a 5 49 cells up to the five micromolar burberine concentration. So it means the patients don't have to go for a very high dose, they can even go with a smaller dose, and burberine is commonly available in the, around the globe on the most of these cist shelves as a nutraceuticals.

13:33 - But it's, it's much advisable. People do take it as a nutraceuticals in their daily routine. However, it is always advisable if any, any patient or any person have a lung cancer. It is good to have a, consultancy first with the clinician so that it should not lead to any kind of the adverse and side effects despite it a nutraceutical. And, and that's why, the ENT role based nano delivery system containing burberine in one

14:00 - of the promising candidate, to treat the lung cancer. This is what is what we have shown in our study. But in our study, what we have clearly shown it is showing a significant inhibition of a 5 49 cell proliferation migration and colon colon formation at even just the five micromolar of the burberine concentration. So in nutshell, I can say that the, our berberine, liquid crystalline nanoparticles formulations, they can potentially actually address the low solubility,

14:32 - the low oral bio viability, the low efficacy, and the adverse side effects of burberine. The PHY is one of a very good polymer that has been used for the novel drug delivery system to incorporate the berberine, and it's a promising delivery candidate, to treat the, lung cancer in future. At this stage, we have, we are successful in developing these, beautiful eff efficacious, nanoparticles

15:00 - and we have only tested so far on the in vitro models. We have also extended our study in the cigarette smoke induced chronic obstructive pulmonary disease, which is also called emphysema. And one of our, that study also is published and we have also shown, shown that these nanoparticles are also effective in treating COPD as well. alongside it means reducing the symptoms of the COPD as well as in lung cancer.

15:26 - But both of these studies are only been done at an in vitro level. At this stage in our lab, we are currently been moving forward to do these studies in the animal models of the lung cancer and COPD and then moving from that, it would be really nice to see if they show really a quite an efficacious therapeutic effectiveness in in vivo models, then it can be taken to the human trials. So, and finally, alongside at this point of time, we are,

15:52 - what we are also doing is we are also trying to encapsulate these, sorry. We are also trying to actually embed these nanoparticles into the leak, into the dry powder inhalers. And we are very closely working with one of the company, which is the respiratory, specific company, and they're helping us actually translating our developed nanoparticles testing into the simulated human models to see the deposition in the lungs where exactly those nanoparticles are sitting, so

16:19 - that an optimal design of the delivery system can be made and can be used further drown down the translational path.

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