Dhrubajyoti Kalita's Talk

Oct 31, 2013 - 17:00

Oct 31, 2013 - 18:00

Creativity Hall (Room 118) Chemical Engineering

Seminars

M.Sc. Organic Chemistry Gauhati University Assam in 2005 Senior Scientific Assistant at Peptide lab Zydus Research Centre Zydus-Cadila Gujarat 2006 (1 year) Ph.D. Chemical Engineering IIT Bombay (2007-2013).

Abstract: Development of a new drug or a new chemical entity involves the tedious medicinal chemistry plus preclinical and clinical research work generating enormous amount of toxic chemicals as byproducts and that too at the expense of nearly billions of dollars. Most of the failed drugs are being eliminated at the Phase II or Phase III of clinical trial. The drugs which are getting discontinued so far though clear these rigorous trials are being discontinued in the long run due to their associated toxicities such as renal failure liver accumulation poor bioavailability etc. This is where the modern techniques of nanotechnology play a vital role; with the scope to reformulate the discontinued and/or cytotoxic molecule by improving its efficiency and reduction in side effect related toxicity. Most small molecule drugs have short blood circulation time and hence it reduces the uptake rate by tumor tissue. In cancer chemotherapy cytostatic drugs damage both malignant and normal cells. Thus a delivery strategy that selectively targets the malignant cells is very much needed. One example of this is the blood-ocular barrier. Due to the complexity of eye the membranes present in it are selective to almost every foreign materials used as drug carriers. The problem becomes more prominent for posterior eye diseases. Retinoblastoma being one such disease in retina still cannot be cured with traditional drug carriers. Carboplatin is one of the most effective anticancer agent after its analogue highly toxic Cisplatin and is effective in a wide variety of cancer such as non small cell lung cancer ovarian cancer and intra-ocular retinoblastoma. Also it is the only effective drug used in systemic chemotherapy for intra-ocular retinoblastoma. After systemic injection Carboplatin is readily excreted from body through urinary excretion where ~50% drug is cleared within 24 hours and hence the therapeutic dose cannot be obtained with a single injection which necessitates the use of multiple injections in chemotherapy and in turn severe side effects such as renal failure hepatotoxicity myelosuppression etc. We hypothesized and experimentally validated that incorporation of hydrophilic carboplatin inside hydrophobic PMMA nanomatrix during thermally induced radical polymerization gives high drug encapsulation efficiency increases the circulation time inside eye improves its (plausible) transport to the retina via vitreous and provides a high therapeutic concentration in the posterior part of eye by sustained release from nanoparticle if injected locally. Briefly following periocular injection in rats the intravitreal concentration of nanoparticulate carboplatin (NPC) was nearly 4 fold higher than the commercially available carboplatin (CAC) concentrations in all the animals as measured by ICP-AES. Animals showed no sign of toxicity in the nearby tissues with undetectable concentrations in blood up to 42 days. Overall the mean vitreous concentration of NPC was greater than CAC in all days. Following our successful attempt in establishment of enhanced intravitreal concentration of carboplatin with NPC compared to CAC in rats the study was extended to human. Objective of the work was to study the tissue safety and intra-ocular distribution of posterior subtenon’s (PST) injected NPC in humans for advanced intra-ocular retinoblastoma as a clinical model. Results indicated an increased facilitated trans-scleral transport of the nanoparticulate form of the drug without any associated ocular tissue damage or systemic side effects post a PST injection. The high concentration achieved in retina and vitreous may be clinically useful for adjunctive treatment of advanced intra-ocular retinoblastoma. Also to achieve active targeting of carboplatin we have reported some novel biocompatible multifunctional core-shell nanoparticles of polyacrylic acid bearing surface conjugated pendant carboxylic acid and amine groups with enhanced hydrophilicity and investigated their ability to carry and deliver Carboplatin in various cancer cells in a target specific manner with detail cellular uptake and efficiency studies.About the speaker: M.Sc. Organic Chemistry Gauhati University Assam in 2005 Senior Scientific Assistant at Peptide lab Zydus Research Centre Zydus-Cadila Gujarat 2006 (1 year) Ph.D. Chemical Engineering IIT Bombay (2007-2013) Thesis submitted. Current Position: Research Scientist at Godrej Consumer Products Ltd. Mumbai.