Our group works on drug delivery systems along lines followed by hundreds of researchers worldwide. We like to think we are different; because (a) we get to work with CSIR-CDRI compounds in the discovery pipeline, and (b) because we have a three-point talisman:-
• Any (reasonable) amount of drug can be delivered to any (reasonably distinct) tissue or cell site, within any (reasonable) time window—the ‘why’ question is more interesting than the ‘how’ question in drug and vaccine delivery.
• Drug delivery is not the end of the problem—the fun starts after drug delivery is achieved.
• Delivery systems proposed by us should be industrially scalable; dirt cheap (not merely cost-effective); and relevant to diseases of socio-economically challenged people.
Most of our research addresses a ‘no-brainer’ question: “if pulmonary tuberculosis (TB) is primarily a lung disease; and if drugs to treat it are to be delivered to the lungs; why do patients have to swallow the medicines instead of inhaling them?” In this pursuit, we practically “wrote (well, edited!) the book” on Inhaled Therapies for TB along with Bernard Fourie and Anthony J Hickey.
We currently have five research projects to make dry powder inhalations (DPIs), and are hoping for funding to investigate whether our approach would work for intracellular respiratory infections in general and COVID-19 in particular. We propose to investigate remdesivir+ ribavarin, lopinavir + ritonavir, hydroxychloroquin + azithromycin, plasmid DNA for transient transfection (gene therapy) with interferons, and vitamin C + vitamin D.
Why we complicate our lives by mostly making fixed-dose combinations (FDC) is a long story about emergence of drug resistance and patient compliance. We also work on host-directed therapies to induce innate immune responses by infected macrophages, including cellular processes like apoptosis and autophagy.
We have standardized industrially-scalable, regulatory-compliant and cost-effective processes to obtain DPI products of established anti-TB medicines (isoniazid+rifabutin and ethionamide+D-cycloserine). Work on kanamycin+pyrazinoic acid is nearing completion. With Gareth W Griffiths at the University of Oslo and his extended network, we are working on sutezolid and some of Andrew Thompson’s brilliant anti-TB candidates from the University of Auckland. We have recently been funded for another exciting and challenging project in collaboration with Shripad Patil and Amit K Singh at NJIL&OMD Agra, Vikas Jain at IISER Bhopal and Urmi Bajpai at Delhi University—to investigate whether we can deploy mycobacteriophages or their lysins as inhaled anti-TB agents.
I have hands-on experience of pharmaceutical product development and drug regulatory filing for formulations of known drugs and New Chemical Entitites discovered at CSIR-CDRI. I can design, conduct and supervise: batch production, process optimization scale-up (QbD) and validation; develop analytical and bioanalytical methods; standard testing protocols (STP); batch release specifications (BRS) and a product monograph; pharmacokinetics, acute, subacute and chronic single and multiple escalating dose (SAD, MAD) studies on rodents and monkeys; and develop an Investigator’s Brochure, design a parsimonious Clinical Testing Protocol of sufficient statistical power,; and carry out statistical analysis of Phase 1 and Phase 2 clinical trial results.
I am fortunate to have developed collaborations with intramural colleagues working on tuberculosis, Leishmaniasis, malaria, diabetes, pulmonary hypertension, chronic occlusive pulmonary disease and contraception and with:
KS Venkatesh for computation and mathematical modeling, and with Dhirendra S Katti on particulate systems; both at IIT Kanpur;
Arvind K Bansal at NIPER, SAS Nagar for hardcore pharmaceutics and pharmacokinetics; and
Amita Jain and Rajiv Garg at King George’s Medical University, Lucknow for work on humans.
We have been funded by DSIR, CSIR, DST, DBT, ICMR, the Royal Society, UK, Tokyo University of Science, Japan, and corporate donors.
Research Projects
5/8/5/38/2019-ECD-I: Indian Council of Medical Research (ICMR). April 2019 to March 2021. An investigational study of mycobacteriophages and their enzymes as new drugs (IND) for treating tuberculosis.
DSIR/CRTD/AH/CDRI/01/2018: Department of Scientific and Industrial Research (DSIR), Government of India. December 2018 to March 2023. ‘Common Research and Technology Development Hub.’ Objectives: pilot-scale, GMP-compliant, regulatory-approved manufacturing facility for pharmaceuticals and regulatory approved Drug Testing Lab and Bioanalytical Site for Clinical Pharmacokinetics, Bioavailability and Bioequivalence Studies.
AMR/lN/112/20l7-ECD-lI: ICMR and Norwegian Research Council. April 2017 to March 2021. ‘Drug targeting for improved treatment of multi-drug resistant tuberculosis (MDR TB).’ Objectives: Inhalations of second-line anti-tuberculosis drugs.
Courses Taught (AcSIR, JNU, NIPER)
Drug Delivery Systems; Drug Regulatory Affairs; Philosophy of Science; Cellular and Molecular Evolution; The Major Histocompatibility Complex; Antigen Processing and Presentation
Research Facilities
R&D –scale GMP and Schedule-M compliant manufacturing area for dry powder inhalations, tablets, capsules, liquid oral/topical products, semisolids, transdermal and sterile preparations.
Spray-drying, spray freeze-drying, supercritical fluid particle formation system, liposome extruder, tangential flow filtration, centrifuges, freeze-dryer, rotary evaporators etc. for delivery system fabrication and finishing.
LC-MS/MS and HPLC for pharmaceutical and biomedical analysis
Stability and photostability chambers, Mastersizer, Zetasizer, Microplate reader, gradient PCR, Gel electrophoresis, DSC, gas pyknometer, polarimeter, refractometer, flame photometer, USP dissolution, disintegration, friability and digital hardness test apparatus etc. for per-monograph pharmaceutical product characterization.
BSL2 and BSL-3 cell culture facilities.
Carreer Highlights
The “Eat-a-banana-sideways” award in B. Pharm; 1987.
R&D Pharmacist at Trends Pharma, Bombay, 1989-90.
Staff Scientist-I at the National Institute of Immunology, New Delhi, 1991-92
DST Young Scientist, 1997
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