Friday, 14 December 2018

New Polymeric Material Developed For Controlled Release Of Two Different Drugs

A bio-compatible polymeric material that promises to help in the simultaneous and extended release of two different drugs from a single platform.

Dr. Uttam Manna (Center) with his research team at IIT Guwahati

A team of researchers at Indian Institute of Technology, Guwahati has developed a bio-compatible polymeric material that promises to help in the simultaneous and extended release of two different drugs from a single platform.

Combination of two or more drugs is increasingly becoming necessary to address drug resistance and treat cancer and neurological disorders. During severe infection, defense mechanism of the body gets activated at multiple levels and single-molecule drugs can’t control multistage complications.

Providing for extended and controlled release of more than one drug molecule simultaneously is challenging. Materials in use to carry molecules tend to have high affinity towards water. As a result, when a drug is delivered, water molecules in the body infiltrate drug-loaded matrix quickly resulting in fast diffusion and release of drug molecules. The new material developed by the IIT-Guwahati team promises to address this issue.

The new polymer mimics the chemistry and features of lotus leaf which make it to repel water. This helps in controlling the rate of infiltration of water molecules and thus allows release of drug molecule in a sustained manner.

Speaking to India Science Wire, Dr. Uttam Manna, a member of the study team, said, “our study has introduced a new general basis for loading and release of various combinations of bioactive molecules. This approach will eventually help to combat challenges related to improved efficacy of drugs and resistance. We hope such material would be useful in controlling multiple diseases as well”. The team is in the process of developing an implant for dual and controlled drug delivery using natural polymers.

The study was performed in the collaboration with Dr. Biman B. Mandal’s research groups, IIT-Guwahati.

Besides Dr. Manna, the team included Adil M Rather, Arpita Shome, Bibhas K Bhunia, Aparna Panuganti, and Biman B Mandal. The study results have been published in the Journal of Materials Chemistry B.

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Simultaneous and controlled release of two different bioactive small molecules from nature inspired single material

Friday, 7 December 2018

Balancing Act at The Edge of Cells: Study

Study suggests each Cell senses the force and regulates the CLIC/GEEC pathway to maintain membrane homeostasis.

BY Ratneshwar Thakur Appeared In BiotechTimes BioVoice

(Left to Right ) Joseph Jose Thottacherry, Prof. Satyajit Mayor and Dr. Mugdha Sathe

We are made up of trillions of cells and they use endocytosis to take up nutrients and growth factors. Endocytosis is a process by which a cell makes small vesicles or bags to take in nutrients from the outside environment. In order to maintain its shape and size, a cell has to maintain the area of its plasma membrane.

Endocytosis decreases the plasma membrane area while the reverse process, exocytosis adds it. A cell needs to balance the two to maintain homeostasis. Imagine removing the membrane bit by bit using endocytosis, the cell will end up shrinking. This means the cell membrane will tense up slowly as the rate of endocytosis is increased. To relieve this tension, the cell needs to lower its endocytosis or increase its exocytosis.

Thus, apart from taking nutrients, endocytosis helps in maintaining the shape and size of the cell.

Now, Prof. Satyajit Mayor’s team has shown how cells regulate this membrane tension using a novel endocytic pathway called the CLIC/GEEC or CG pathway. The study done by lead author Joseph Jose Thottacherry shows that the CG endocytosis is intimately connected to membrane tension by sensing and responding to changes in membrane tension.

“We have shown that increase in endocytosis increases the membrane tension. When we perturb the pathway to decrease endocytosis it decreases the tension. Thus, addition and removal of membrane directly influence the tension of membrane” said Joseph Jose Thottacherry. The results of this study were published in the journal Nature Communications.

Traditionally, endocytosis requires a coat protein to bend the membrane that forms a cage-like structure, and another protein to cut the vesicle. However, the CG pathway, unlike the traditional pathway, works without the coat raising the question, how would a cell bend its membrane for making vesicles?

This was worked out in another published report in Nature Communications  from Prof. Mayor’s lab by lead authors Dr. Mugdha Sathe & Gayatri Muthukrishnan. They found that in the absence of a coat, the cell uses membrane curvature sensing proteins that recognize convex and concave kind of curvatures. They find two proteins called PICK1 (convex) and IRSp53 (concave) that help in vesicle formation by bending the membrane.

Prof. Mayor said, “Our study suggests each cell senses the force and regulates the CLIC/GEEC pathway to maintain membrane homeostasis. If the force goes higher, the CLIC/GEEC pathway is shut down helping the membrane relax while if tension goes lower, endocytosis increases and extra-membrane is taken in.”

So what is this CLIC/GEEC pathway important for? 

Earlier studies have shown that many viruses use this pathway to enter the cells. This pathway is also involved in fruit fly wing development and cell migration. Now, it has been shown that it can help with plasma membrane homeostasis.

Since this pathway is involved in cell migration, it can be involved in spreading of cancer cells to different organs during metastasis or immune cells chasing pathogens. Thus, these two studies are promising and show the importance of understanding non-traditional pathways for their potential translational value.

This study was carried out at National Centre of Biological Sciences (NCBS), Bangalore. The research work was funded by Wellcome Trust-DBT India Alliance and Dept. of Science and Technology (DST), Govt. of India.

This report was prepared with the help of lead authors Dr. Mugdha Sathe and Joseph Jose Thottacherry.

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