Ongoing Projects
Title : Development of glycogen synthase kinase-3β inhibitors for neurogenesis in neurodegenerative disorders
Principal Investigator

  • Dr. M Ramanathan, Principal PSG College of Pharmacy

Co-investigators

  • Dr. P Rani, Professor, Department of Biotechnology, PSG College of Technology
  • Dr. S Kabilan, Professor, Department of Chemistry, Annamalai University, Chidambaram

Funding Agency: DBT

Funding Amount : 66.11 Lakhs

Date of Sanction and Duration: April 2011 for a period of 3 years

Abstract

Glycogen synthase kinase (GSK-3) is a protein kinase present in two isoforms GSK-3 α and β which are ubiquitously expressed and constitutively active in many physiological processes including cell proliferation, metabolism, gene expression and apoptosis. Among these two isoforms, GSK-3β has been expressed mainly in nervous tissue and implicated in molecular pathogenesis of human disease. Currently GSK-3β has been focused for the therapeutic treatment of more prevalent diseases like type II diabetes, Alzheimer’s disease, stroke, bipolar disorders and repopulating the transplanted hematopoietic stem cells. Diverse molecules have been tested preclinically for GSK-3β inhibition and have shown efficacy against neurodegeneration and currently no GSK-3β inhibitors has been approved for clinical use. Majority of these molecules reported as GSK-3β inhibitor have been administered through intraperitoneal or intravenous routes. Molecules acting through oral route of administration and targeting specific molecules and which can cross blood brain barrier are required to have beneficial effects which is currently lacking. The objective of the present study is to study the GSK protein kinase isoforms on their ligand binding sites, design, synthesize and evaluate GSK-3β inhibitors in neurodegenerative conditions. The differences between GSK-3β α and β in ligand binding domain will be identified.

The essential features required for GSK- 3β binding will be identified using Glide and Strike programs from Schrodinger. The various unique conformations required for GSK-3β inhibitions will be studied and validated by using known standard inhibitors of GSK-3β. New molecules will be designed and the ligands which show good interactions with the target & binding energy will be selected for synthesis. Molecules identified in virtual screening will be considered for phase II of the study. Synthesized compounds will be evaluated for their inhibition potency against GSK-3β using human GSK 3β expressed insect cell lines. The neurogenesis property of the new molecules will be evaluated by immunohistochemistry staining and image analyzer. Alzheimer’s disease and stroke model will be employed to assess the neuroprotective activity of the molecule based on in vitro study. Molecular mechanism using immunoblot and immunohistochemistry data will be used to support GSK-3β inhibitory activity. It is a novel proposal; many leading laboratories are working worldwide using GSK-3β as a novel protein kinase target, to treat neurodegenerative disorders by controlling cell signaling pathways and improving neurogenesis. The expected outcome of the project will be the development of new chemical entities which can be patented and commercialized with the help of pharmaceutical companies.

Title : Development of Nanoparticle drug delivery system for Alzheimer’s disease.
Principal Investigator

  • Dr. C Vijaya Raghavan, Vice-Principal, PSG College of Pharmacy

Co-investigators

  • Dr. M Ramanathan, Principal, PSG College of Pharmacy

Funding Agency: ICMR, New Delhi

Funding Amount : 25 Lakhs

Date of Sanction and Duration: 20-Oct-2010, 3 Years

Abstract

Alzheimer’s disease (AD), a neurodegenerative disorder of the elderly, is the most prevalent form of dementia. As of today, this number is reported to be 35 million-plus people worldwide and is thought to reach approximately 107 million people by 2050. The drug-development mission for AD suffers from an imbalance between central nervous system (CNS) drug discovery and CNS drug delivery. Owing to the presence of the blood-brain barrier (BBB), polymeric biocompatible drug carriers have been utilized as vehicles for CNS drugs in order to help them penetrate the BBB for many applications such as cancer therapy, but the field of nanoparticulate drug carrier technology is not well developed in AD research. Nanoparticles are polymeric particles made of natural or artificial polymers ranging in size between 10 and 1000 nm (1 μm). Compared with other colloidal carriers, polymeric nanoparticles present a higher stability in biological fluids. Studies suggest nanoparticles adhere to the cell membrane and subsequently escape efflux by the P-gp effluxsurface modifications can deliver drugs of interest beyond the BBB for diagnostic and therapeutic applications in neurological disorders such as AD. Thus Polymeric nanoparticles are promising candidates in the investigation of AD because they are capable of opening tight junctions crossing the BBB, have high drug loading capacities to minimize toxicity and side effects, and effectively target the mutagenic proteins of AD.

Title : Development of Solid Lipid Carrier to target brain cells for neuro-protective action of Curcumin.
Principal Investigator

  • Mr. SM Habibur Rahman, Associate Professor, PSG College of Pharmacy

Funding Agency: AICTE, New Delhi

Funding Amount : 6.3 Lakhs

Date of Sanction and Duration: May 2011 for a period of 2 years.

Abstract

Solid lipid carrier (SLC) loaded Curcumin will be developed by high speed homogenization and ultra sonication. The developed formulation will be characterized using standard protocols. The neuroprotective activity of the SLC loaded curcumin will be evaluated using cell lines challenged with hypoxia / glucose deprivation. The outcome of the project will be to develop a curcumin formulation that will have enhanced bioavailability, cross the BBB, and target the brain cells for the treatment of neurodegenerative conditions.

Title : Preclinical evaluation of modified estrogen receptor beta agonists for prostate cancer treatment.
Principal Investigator

  • Dr. M. Ramanathan, Principal, PSG College of Pharmacy

Co-investigators

  • Dr. V. Ramamurthy, Professor and Head Department of Biotechnology, PSG College of Technology
  • Dr. S. Kabilan, Professor, Department of Chemistry, Annamalai University, Chidambaram

Funding Agency: DST

Funding Amount : 30.15 Lakhs

Date of Sanction and Duration: May 2011 for a period of 2 years.

Abstract

ERβ agonist selective to ERβ can effectively be used in the treatment of prostate cancer. Currently, there is no selective ERβ agonist in the market. In an earlier DST sponsored project (SR/SO/HS-22/2006 dt 08.02. 07), we examined isoflavone scaffold, a simplified version of glabridin in order to identify ERβ selective ligands. Based on molecular modeling studies, we identified eleven modifications of isoflavones synthesized them checked for its anticancer activity in PC3 cell lines. Few of these new lead molecules have shown better efficacy and the results are promising. To further strengthen these prospective chemicals generation of data on pharmacokinetics, toxicological and safety profile is desirable. Hence in the present project, we intend to evaluate the efficacy of the compounds on wider panel of prostate cancer cell lines like LNCaP and DU-145 and for safety in normal cell lines like L929 lung fibroblast and L6 rat skeletal muscle. The selectivity profile of the compounds will be studied with radio labeled receptor binding studies and specific estrogenic response studies in ERβ transfected PC-3 cell lines. The best molecule’s ability to induce apoptosis will be studied by evaluating the caspase-3,8 and 9 activities in PC-3 cells. Gene expression studies of bcl-2, bax, c-myc, cyclin D-1, cyclin E will also be evaluated in real time PCR to elucidate the mechanism of action of the synthesized compound. The best molecule will be further evaluated in vivo models like uterotrophic assay and xenograft nude mice. In addition, the ADME property and toxicity studies will be performed to confirm the drugability and safety of the compounds. The possible outcome will be new therapeutic molecule for prostate cancer and its molecular mechanism through which it exhibits anticancer activity.

Date of Initiation : Sept 2012

Title : Androgen receptor mediated drug development to treat Prostate Cancer.
Investigators

  • Dr. Jibon Kotoky, Associate Professor II, Institue of Advanced Study in Science Guwahati, Assam
  • Dr. M. Ramanathan, Principal, PSG College of Pharmacy
  • Dr. S. Kabilan, Professor, Department of Chemistry, Annamalai University, Chidambaram

Funding Agency: DBT, Twinning Project, New Delhi

Funding Amount : 46.41 lakhs

Date of Sanction and Duration: May 2011 for a period of 2 years.

Abstract

Prostate Cancer is the second major cancer disease that affects male and mortality rate is high due to multiple pathology of the disease and development of drug resistance due to receptor mutations. This project aimed to address this problem related to resistance development and to develop new chemical entities to treat patient who is not responding to standard care. It is a novel approach and successful development of this product can increase the life expectancy of the cancer patient. It also opens an avenue for exchange of technology between institutions and establishment of labs to synthesize and standardize new chemicals, cell culture and molecular biology research. Also, this may lead to development of Process and a NCE(s) for the treatment of Prostate Cancer from the Project work.

Title : Glabridin derivatives for the estrogen receptor β mediated growth control of the prostate cancer cells.
Principal Investigator

  • Dr. M Ramanathan, Principal, PSG College of Pharmacy

Co-investigators

  • Prof. AK Chandrasekharan, Director, PSG College of Pharmacy
  • Dr. V Ramamurthy, Professor and Head, Department of Biotechnology, PSG College of Technology
  • Mr. C Sabarinath, Lecturer, Department of Biotechnology, PSG College of Technology

Funding Agency: DST

Funding Amount : 20.99 Lakhs

Date of Sanction and Duration: October 2010.

Abstract

Phytoestrogens can mediate biological activity through estrogen receptors and hence can find appropriate applications. Recent reports indicate development of selective ER beta (ERβ) agonist for cancer treatment due to their nonproliferation effects on breast and prostate tissues. Glabridin, a polyphenolic flavonoid obtained from the root of Glycyrrhiza glabra (licorice), possess estrogenic activity and has also been found to have anticancer action possibly mediated through protein kinase inhibition. Hence the role of ERβ in this process is suspected but yet to be established. Further, glabridin is having structural resemblance to that of genistein, a phytoestrogen recently reported to have anticancer activity. The objective of our proposal is to increase the ERβ selectivity of glabridin by structural modification studies through computational drug design. These compounds will be synthesized and authenticated for their anticancer property in prostate cell lines. The possible outcome from the project will be the development of new therapeutic molecules for prostate cancer which is increasing in prevalence globally.

Title : Standardization, validation and development of herbal formulation for treatment of neuropathic pain.
Principal Investigator

  • Dr. M Ramanathan, Principal, PSG College of Pharmacy
  • Dr. Ramesh R Varier, Managing Director, Arya Vaidya Nilayam

Co-investigators

  • Dr. V Sankar, Professor, Department of Pharmaceutics, PSG College of Pharmacy
  • Mr. SM Habibur Rahman, Associate Professor, Department of Pharmaceutics, PSG College of Pharmacy

Industrial Partner: Arya Vaidya Nilayam, Madurai

Funding Agency: DST – DPRP

Funding Amount : 51.2 Lakhs

Date of Sanction and Duration: Oct 2008 for a period of 3 years.

Abstract

Neuropathy is characterized by nerve dysfunction and improper impulse conduction. It is observed in patients affected withmetabolic disorders and related diseases. Neuropathy is a commoncomplication of IDDM and NIDDM patients. Currently usedmedications are aimed to modify the mechanisms of neuropathic pain.But drug and non drug therapies provide complete or partial relief of pain in only about half of patients, leaving considerable room for improvement. Specific guidelines for the treatment of neuropathic pain have not yet been developed. So there is a need for the development of drug for diabetic neuropathic pain based on Ayurvedic principles. Indian system of medicine is having much scope for the treatment of many complications, so finding a solution for diabetic neuropathic pain from Ayurvedic origin and validating the mechanism of the herbs will be useful to avoid neuropathy related complications.

Title : Phytochemical, Pharmacological and toxicological investigation of Aegle Marmelos for a new product.
Principal Investigator

  • Dr. S Murugesan, Scientist-E, IFGTB, Coimbatore

Co-investigators

  • Dr. M Ramanathan, Principal, PSG College of Pharmacy

Funding Agency: Indian Council of Forestry Research and Education

Funding Amount : 13.43 Lakhs

Date of Sanction and Duration: Oct 2008 for a period of 3 years.

Abstract

The Bael leaves absorb foul gases from the atmosphere and keep it clean and salubrious while the raw bael fruit has purgative effect. The ripe fruit has cooling effect and produces constipation. Raw bael fruit is taken for treatment of ailments such as arthritis and gout. Bael also helps to sharpen the intellect and concentration of mind. The medicinal value of Bael fruit is attributed due to presence of tannins. Ripe bael fruit taken with fresh cream (butter) and sugar candy powder sharpens concentration and intelligence. Since the preliminary screening has brought out promising results, further investigation is required to convert this plant material into a useful medicinal product. As Bael is also a holistic plant and has a wide range of pharmacological properties, the objective of the present study is to analyze the adaptogenic property and behavioral alterations in rats. The specific objective of the present study is to standardize of Bael extracts and identify the active constituents. Further pharmacological studies to substantiate the preliminary studies, toxicity studies including acute and sub-acute toxicity studies, Preformulation studies and development into a pharmaceutical product will also be undertaken.

Minor Projects (Completed)

The minor projects are student projects recognized and awarded as the best project proposal with a cash prize ranging from Rs 5000 to Rs 10000 by Tamilnadu State Council for Science and Technology and Tamilnadu Pharmaceutical Sciences Welfare Trust, Chennai. These small appreciations and awards really encourage our students to aim high and to continue his/her research. We at PSGCP take this opportunity to sincerely thank these organizations. The following are the completed and ongoing minor projects at PSGCP.

2007

M. Pharm student [Mr. V Harikrishnan] got a project worth Rs 10000 from the Tamil Nadu State Council for Science and Technology. Dr. V Sankar was the Research Supervisor for this project entitled “Formulation and evaluation of Dexamethasone sodium phosphate Nanoparticles for post cataract treatment”.

2008

M. Pharm students [Mr. K Velayutham &#38 Mr. C Praveen] got a project worth Rs. 5000/- from The Tamilnadu State Council for Science and Technology, Chennai. Dr. V Sankar, HOD Pharmacy Practice PSGCP, was the Research Supervisor for the work entitled “Targeting Salbutamol to Lungs through Niosomes”.
M. Pharm student [Mr. John R] got a project worth Rs 5000 from the Tamilnadu State Council for Science and Technology. Dr. Vijayaraghavan was the Research Supervisor for this project entitled “Site specific controlled release Capecitabine microspheres for colon cancer”.

M. Pharm student [Mr. K Velayutham] got a project worth Rs 6000 from the Tamil Nadu Pharmaceutical Sciences and 26Welfare Trust. Dr. V Sankar was the Research Supervisor for
this project entitled “Tissue distribution and Pharmacokinetics of Salbutamol Proniosomes for lungs”.

2009

M. Pharm student [Mr. Arul Kumar B] got a student project worth Rs. 8000 from the Tamilnadu Pharmaceutical Sciences Welfare Trust. Dr. Vijayaraghavan was the Research Supervisor of this project entitled “Brain targeted delivery of Betulinic acid loaded Nanoparticles for tumor”.

M. Pharm student [Mr. Sivakumar R] got a student project worth Rs 10000 from the Tamil Nadu State Council for Science and Technology. Dr. Vijayaraghavan was the Research Supervisor for this project entitled “Colon cancer targeted delivery of capecitabine using poly (D,L- Lactic acid coglycolic acid) Nanoparticles”.

M. Pharm student [Mr. Antony Noby] got a project worth Rs 10000 from the Tamil Nadu State Council for Science and Technology. Dr. V Sankar was the Research Supervisor for this project entitled “Carboplatin niosomes for enhanced delivery to cancer cells”.

2010

M. Pharm student [Ms. Kalpana Eluri] got a student project worth Rs. 8000 from the Tamilnadu Pharmaceutical Sciences Welfare Trust. Mr. KG Prasanth is the Research Supervisor for the work entitled “Evaluation of the effect of tetrahydrocurcumin in HMG-CoA reductase and lipoprotein lipase enzymes in high fat diet induced hypercholesteremia in rabbits”

M. Pharm student [Mr. Ranjith Kumar] got a student project worth Rs. 7000 from the Tamilnadu Pharmaceutical Sciences Welfare Trust. Mr. B Balaji is the Research Supervisor of this project entitled “Evaluation of mechanism of action of Nerunjil in neuropathic pain perception in experimentally induced diabetic model”

M. Pharm student [Mr. Vimal KR] got a student project worth Rs 8000 from the Tamilnadu Pharmaceutical Sciences Welfare Trust. Dr. V Sankar is the Research Supervisor of this project
Entitled “Enhancement of follicular delivery of finasteride in niosomal and proniosomal gel from for treating androgenetic alopecia.”

Travel grants received for international conferences

  • Dr. C. Vijaya Raghavan received a travel grant of Rs. 72,000/- from Indian Council of Medical Research (ICMR) for presenting a research paper in the International conference of Colloids and Nanomedicine 2012, 15th-17th July, 2012, Amsterdam, The Netherland.
  • Dr. C. Vijaya Raghavan received Rs. 54,000 grant from the Department of Science and Technology, New Delhi for delivering the talk in EHRLICH II, 2nd World Conference on magic bullets, October 3-5, 2008 Nurnberg, Germany.
  • Dr. V Sankar received Rs 20,000 from the IPA International Ramabhai Foundation grant for travelling to the Asian Pharmaceutical Association Congress at Singapore.
  • Dr V. Sankar, Profesor and Head Department of Pharmacy practice selected by WHO, received grant to undergo one month training in practicing pharmacy in Paediatrics speciality in Canada