Category: News

Pillalamarri Srikrishnarka
Tampere, Finland

Picture a world where handling diabetes is as simple as applying a bandage—a solution that adapts to your body’s requirements, eliminating the hassle of frequent injections and glucose checks. It definitely has a forward-thinking vibe, doesn’t it? The future is upon us, driven by an exciting innovation: the glucose-responsive microneedle patch.

Researchers have recently made a significant advancement by designing a microneedle patch that could transform insulin delivery for individuals living with diabetes. Researchers, spearheaded by Shiqi Wang and their team, have unveiled an innovative microneedle system with a remarkable capacity for insulin. This system is designed to react to fluctuations in blood glucose levels, ensuring extended and accurate management of glycemic control.

What is the Process Behind It?

The idea is straightforward yet brilliant: a tiny patch, equipped with minuscule microneedles, that can deliver insulin when blood sugar levels increase and stop the release once levels stabilize. Every microneedle features a core of solid insulin powder, carefully encased in a polymer shell that responds to glucose levels. After the patch is applied, the microneedles effortlessly enter the skin, continuously tracking blood sugar levels in real time.

As blood glucose levels rise, the polymer shell of the patch expands as glucose-boronate complexes are formed. This increase promotes a faster release of insulin from the needle core. When glucose levels normalize, the shell tightens, which in turn slows down the release of insulin. This innovative system replicates the natural function of a healthy pancreas, removing the necessity for constant monitoring or numerous daily injections.

What Sets This Patch Apart?

One of the major hurdles in creating a microneedle patch for insulin delivery has been the challenge of incorporating a sufficient amount of insulin into a patch that remains compact enough for practical application. The conventional approaches restrict insulin loading capacity to under 6%, which falls short for human use. This innovative design successfully incorporates over 70% insulin into the patch, representing a significant advancement that enables up to 48 hours of glycemic control in animal models such as diabetic minipigs.

This innovative treatment is a breakthrough, particularly for individuals with type 1 diabetes, who traditionally need to administer insulin multiple times daily. Additionally, by administering insulin based on glucose levels, the likelihood of hypoglycemia—a serious condition resulting from low blood sugar—is significantly minimized.

The Research Underlying It

The distinctive feature of this system lies in its glucose-sensitive polymeric shell that encases the insulin core. The shell consists of a polymer matrix incorporating phenylboronic acid (PBA), a compound that interacts with glucose to form negatively charged complexes. When blood sugar levels rise, these charges lead to the swelling of the shell, which results in the release of insulin. When glucose levels decrease, the shell constricts once more, preventing additional insulin from being released. It’s an adaptable and responsive system crafted to meet the body’s immediate requirements.

This technology not only provides enhanced control but is also designed to be minimally invasive. Conventional methods of delivering insulin typically require injections, which can be uncomfortable, pose infection risks, and frequently result in low adherence from patients. The microneedles in this patch are incredibly tiny, ensuring a painless experience and allowing for easy removal without any leftover residues that could lead to irritation or allergic reactions.

Extended Management in Animal Studies

Research involving diabetic mice and minipigs demonstrated that the microneedle patch effectively sustained normal blood sugar levels for as long as 48 hours, eliminating the requirement for manual insulin injections. This performance marks a notable improvement over previous microneedle versions and signifies a substantial advancement for clinical applications. The research indicated that the microneedles are capable of releasing insulin at varying rates based on the body’s glucose levels, demonstrating the system’s effectiveness in managing blood sugar fluctuations

The Journey Forward

This technology has demonstrated impressive potential in animal studies, yet there are still necessary steps to be completed before it can be accessible to humans. The next essential step involves human clinical trials. Should it prove effective, the glucose-responsive microneedle patch may stand as a groundbreaking development in diabetes management in recent years—liberating individuals from the relentless demands of glucose tracking and frequent injections.

Currently, the findings from Wang and the team at Zhejiang University offer optimism to countless individuals managing diabetes. A cutting-edge, adaptive patch designed to manage blood sugar levels and administer insulin exactly when required may soon become a reality.

This advancement highlights the way creativity at the crossroads of bioengineering and medicine is reshaping the future of healthcare. With each new study that emerges, we are reminded that the path to transforming diabetes care may be lengthy, but the progress we are making is truly thrilling.

This piece highlights the innovative nature of the glucose-responsive microneedle patch was published in ACS Nano (Glucose-Responsive Microneedle Patch with High Insulin Loading Capacity for Prolonged Glycemic Control in Mice and Minipigs | ACS Nano)

Pillalamarri Srikrishnarka

Chennai, India

Researchers from three different nations concluded in a recent study that air pollution, particularly PM2.5, could be a serious concern for increasing lung cancer patients. They found that ambient air pollution was related to an increased risk of EGFR-driven lung cancer in 32,957 non-smokers and light smokers. In addition, they also discovered that there was a considerable flow of macrophages into the lungs of the mice when the mices were subjected to simulated air pollution. One of their key findings is that even three years of exposure to PM2.5 are enough for a person affected by EGFR-driven lung cancer without DNA damage. This finding has alarmed researchers.

Let’s take a quick look at a few of the fundamental notes I’ve taken to grasp better what cancer is and to study a few of the terms used in the post before we go right into pieces themselves.

Since we know that mutations in healthy cells can cause cancer, the first step in treating the disease is determining what causes these mutations. The initial stage of cancerous development is a step known as the promoter step.

“Epidermal growth factor receptor (EGFR) is a transmembrane protein; overexpression of this factor suggests the presence of cancer, and under expression suggests the possibility of Alzheimer’s. For the identification of this protein, the Nobel Prize in Medicine was conferred.”

Figure 1. (A and B) Representative immunohistochemistry (IHC) images of human EGFRL858R in ET mice exposed to PBS or PM at 10 weeks. C Representative diagram of spatially segmented human EGFRL858R-positive clusters in lung lobes, with the size of clusters proportional to EGFRL858R cell number at 10 weeks. Copyright © 2023, The Author(s), under exclusive license to Springer Nature Limited.

In a credible study, researchers found that the risk of developing lung cancer rose directly to PM2.5 in the air. They also found that this pattern held throughout all of the East Asian nations studied, in contrast to the native population of the UK.

For researchers to obtain further clinical insights into the progression of lung cancer, they genetically changed a few mice, caused cells to begin the mutation process, and then subjected the animals to ambient air pollution for ten weeks. Due to the exposure to PM, they observed an increase in the adenocarcinomas and aggressive CCSP-rtTa; TetO-EGFR model of doxycycline inducive hyperplasias in an adenoviral-CMV-Cre Kras model of lung cancer.

“They eventually concluded that exposure to PM promotes tumour progression in both oncogenic Kras and EGFR models of lung adenocarcinoma tumours.”

In addition, the evidence that was provided about the clonal dynamics shows that because of PM exposure, EGFR mutant cells grow with the capacity to form a tumour, and an increase in the proliferation rate of EGFR mutant cells demonstrates this.

The IL-6-JAK-STAT pathway is responsible for the mutation, which begs the question, “How does the mutation take place?” Only after exposure to PM were the immune response pathways of inflammation and the allograft response pathway shown to be elevated. Because of the exposure to PM, the expression of the genes for interleukin-1beta (IL-1beta), GM-CSF, CCL6, NK-kB, and epithelial-derived alarmin IL-33 increased. AT2 cells are a candidate cells for the beginning of the adenocarcinoma process in the lung.

“When exposed to PM, lung macrophages release inflammatory cytokines, which is central for tumour promotion. In addition, the IL-1beta signaling is required to promote PM-mediated EGFR-driven lung adenocarcinoma.”

The researchers went on to verify this notion using human lung tissue from 195 people who did not have cancer. They discovered that EGFR-driven mutations might be present in histologically normal lung tissues, even in patients who did not have the same mutations picked during the NSCLC carcinogenesis process. This suggests that EGFR can cause mutations in lung tissue.

The presented data is extremely concerning, and immediate urban replanning is required to stop the further growth in air pollution. However, it is not a sustainable solution to protect oneself from air pollution by donning a mask; rather, a concerted effort by scientists, engineers, city planners, medics, and people in general to battle air pollution is the way ahead.

Reference:

Hill, W., Lim, E.L., Weeden, C.E. et al. Lung adenocarcinoma promotion by air pollutants. Nature 616, 159–167 (2023). https://doi.org/10.1038/s41586-023-05874-3

Pillalamarri Srikrishnarka

Chennai, India: Circulating tumor cells travel from tumor throughout the body and create colonies in different parts of the body leading to recurrence of cancer. This process is also known as metastasis. Imaging these traversing cancer cells and in vivo destroying them without affecting the other cells of the body could potentially prevent the recurrence of cancer.

In this regard there are reported routes of in-vivo capturing these CTC and preventing them from traveling. Of which, inserting of a temporary microchip inside the body which harvests these CTs for extended periods of time. Since the chip is very small in size, the amount of blood harvesting is very small and is time consuming. The other method is by injecting magnetic nanoparticles which interact with these CTs and subsequently captured by controlling the magnetic field. In the third method, an implant typically that has been biofunctionalized is placed inside the body that can capture these CTs and prevent them from spreading throughout the body and initiate the formation of colonies.

To address some of the difficulties faced during the capturing of CTs, recently Wang and co-workers from the Southern University of Science and Technology utilized a functionalized flexible catheter having electrospun nanofibers for capturing these CTs. A liquid metal-polymer conductor was first sprayed onto the catheter and was the surface was sealed using a sealant which helped in making the surface conducting. The top surface of the catheter was given positive potential and the bottom layer was applied with a negative potential. This catheter was used a substrate for collecting electrospun nanofibers in such a way that, as the catheter enters the body, the fiber coating dosen’t get damaged.

The surface of the nanofibers were further functionalized to make them biosafe. These fibers acted as a net to capture all the floating CTs and they were killed by applying potential. They found that around 48 % of the CTs were captured in the presence of the electrospun nanofibers and without the coating it was just 2 %.

“The blood vessel in the LM/NF-catheter group still remained unobstructed and was functioning well. No noticeable morphological changes of the major organs were observed, indicating that there was no observable toxicity or side effects.” claimed the authors.

​​”As we have set the voltage for IRE at a low level, only the cells on the surface of the catheter can be killed, and the IRE could not damage the cells 1 mm away from the catheter. Even though some blood cells are on the surface of the catheter and killed by IRE, this small amount of hemolysis will not significantly affect the normal physiological function of the body.”- was observed by the authors.

This work was concluded by “this project can provide an alternative method for reducing the load of CTCs and other harmful exosomes in patients and has a broad prospect in clinical application to prevent tumor metastasis and recurrence.”

These results were published in ACS NANO (10.1021/acsnano.1c09807)

Pillalamarri Srikrishnarka,

Chennai, India: “Plastics have become an integral part of our life” is an understatement, with a global market worth 430 Billion USD! is one of the richest industries and is expected to grow to 600 USD by 2026. In view of current times where wearing of masks and protecting oneself from COVID has become a basic necessity, these number can easily skyrocket.

After it’s purpose has been solved, plastics generally end up as debris both in landfills and the oceans. With is inertness and high half-life, these plastics don’t degrade, however they break down into tiny fragments forming micro and nano plastics. With potential health risks from these nanoplastics, the health and environmental factors need to be understood ASAP.

Recent evidences on the presence of these micro plastics in fish(Accumulation, Tissue Distribution, and Biochemical Effects of Polystyrene Microplastics in the Freshwater Fish Red Tilapia (Oreochromis Niloticus). Environ. Pollut. 2018, 238, 1−9, Brain Damage and Behavioural Disorders in Fish Induced by Plastic Nanoparticles Delivered through the Food Chain. Sci. Rep. 2017, 7, 11452.) and the human fetus is alarming, major reforms are needed for the safe disposal of plastics globally.

Liu et al., investigated the interaction of nanoplastics with the brain and for the first time they observed the deposition of plastics in the brain by inhalation. For this study, they chose polystyrene beads of the size range 80-200 nm and functionalized with acid and amine groups and their bio interactions were studied. With 7-day exposure to nanoplastics aerosols, these plastics have successfully penetrated the blood brain barrier and liver. Amine-functionalized polystyrene particles absorbed easily through the nasal mucosa compared to that of acid-functionalized polystyrene beads. Such accumulation in the brain could lead to inflammation that could further cause brain disorders and cognitive delusions. In controlled environment, they observed that mice under exposure to plastic aerosols had reduced average movement speed when compared to that of control.

They have concluded that with an understanding of the pathway of plastics into the brain, the focus could be on the block of these pathways and prevention of the internalization and deposition in the brain can be done. 

These results have been published in ACS Nanoletters ( Nano Lett. 2022, 22, 1091−1099)

Pillalamarri Srikrishnarka

Dielectica traverses through the literature on this topic – and summarizes as they appear.

Keywords: Reverse Osmosis, Membrane Desalination, Clean Water, Energy Harvesting

Chennai, India: With exponential growth in population and increased living standards, there is a rise in demand for energy and clean water. Desalination is one of the promising routes in converting saltwater to clean water, due to its huge abundance. Reverse osmosis (RO) is predominantly used in extracting pure water from sea or ocean water. Although RO is being widely used commercially, however, it consumes a lot of energy. Water wastage is also an issue in this technology. Apart from RO technology, several other desalination techniques have been come up in this context. Membrane distillation is a popular one among these techniques.  

Membrane distillation, which works on utilizing low-grade thermal energy, is an alternate route in obtaining clean water. So, let’s understand how this works. There is a porous hydrophobic membrane, one side of the membrane is hot and the other side is cold. Due to this temperature difference, the water evaporates on the hot side and diffuses through the membrane. Finally, it is condensed at the cold side. Straub et al. utilized this technique for generating electricity also. Typically, the cold region of the membrane distillation process is pressurized. As the condensation increases, water volume rises which results in increased hydraulic pressure. This resulting pressurized flow was used to drive turbines for generating electricity, thereby converting the low-grade thermal energy to electricity and also obtaining clean water in this process. [1, 2] With the advent of nanotechnology, scientists are successful in generating ~ 1 V by water evaporation even at room temperature [3].

In an effort to obtain both clean water and also electricity, Huang et al., fabricated a simple device having a Teflon membrane and porous alumina powder-coated membrane. [4] The Teflon membrane is placed between the hot and cold feed and the hot vapors diffuse from the hot feed side to the cold region. The alumina-coated membrane offers huge resistance for the cold water to pass through and with increased condensation, the volume of cold water keeps on increasing. This results in increased hydraulic pressure on one side of the alumina membrane compared to the other side of the cold reservoir. This drives the water into the cold reservoir through the membrane. As the cold water is forced through the negatively charged micro-pores of the alumina membrane, the hydroxide ions present in water are repelled at the entrance due to electrostatic repulsions. The remaining hydronium ions diffuse through the permeate channel resulting in a streaming potential. This generated potential from each side of the alumina membrane is extracted using silver mesh electrodes.

Using this device, researchers were successful in extracting 13.4 kg m^-2 h^-1 of flux and 147 micoW m^-2 of power density capable of lighting up a LED. Therefore, such kind of device is aiming to provide a solution to two major global problems, clean water, and energy.

References:

[1] A. P. Straub et al. Nat Energy 2016, 1, 16090.

[2] A. P. Straub et al, Environ. Sci. Technol. 2017, 51, 21, 12925–12937.

[3] G. Xue, Nature Nanotech 2017, 12, 317–32.

[4] L. Huang et al. J. Mater. Chem. A, 2021, 9, 27709-27717.