The main goal of the proposed work is to develop a polymeric delivery system for drug, 5-Flurouracil and siRNA, a gene suppresser capable of increasing the therapeutic index of the drug, devoid of adverse effects in colorectal cancer. SiRNA can effectively silence a wide variety of mutated oncogenes such as K-Ras, mutated p53, APC/DCC genes. The guardian of the genome, p53, is inactivated by point mutations in more than 45 - 60% of human colorectal cancers. Biodegradable polymers and copolymers based implant and oral drug delivery system have been found to posses important potential therapeutic applications in controlled release of drugs and site-specific delivery. In this proposal we are introducing oral drug delivery systems which can deliver the drug as well as siRNA in a controlled manner.

Methacrylic based copolymer system in drug delivery shows the property of pH-sensitive drug releasing behaviour in colon. Methacrylic based copolymer was developed by microemulsion polymerisation technique and characterized spectrophotometrically. In vitro drug 5-Fluorouracil (5-FU) release studies and biological evaluation of the nanogel confirmed that the gel can be successfully used as an efficient vector for pH sensitive and controlled delivery of drugs specifically to colon.

Fig 1. Methacrylic Acid copolymer was synthesized for capsule coating

The main goal of the proposed work is to develop a polymeric delivery system for paclitaxel and curcumin, capable of increasing the therapeutic index of the drug, devoid of adverse effects. Biodegradable Polyethyleneglycol (PEG) coated naoparticles have been found to posses important potential therapeutic applications as injectable colloidal systems for the controlled release of drugs and site-specific drug delivery. In this proposal we are incorporating two properties to increase the long term circulation of polymer nanoparticles to reach the tumor tissue, with specific recognition capacity.

In this project our results indicate that nanoparticle-encapsulation improves the solubility of curcumin in aqueous medium and gel form, which further enhances its efficacy to induce apoptosis in cancer cells. Poly (lactide-co-glycolide-polyethylene glycol [PLGA-PEG] folate based nanoparticles gives a better apoptosis compared to their free counterpart. Tumour reduction study conducted using HeLa xenograft models to check the chemosensitizing efficacy of nanocurcumin in paclitaxel chemotherapy in female NOD-SCID mice demonstrates that folic acid conjugation of PLGA nanocurcumin improves the chemosensitizing efficacy of curcumin.

Fig 2. Representative images of NOD-SCID mice bearing HeLa xenograft tumors, after 4 weeks of treatment.

The main aim of this work is to fabricate a three dimensional highly porous scaffold which can function as an implant material or a suitable substitute for vascular graft. For this, the fabricated scaffolds were incorporated with different cell adhesion peptides (prepared by Fmoc strategy) and cells are seeded with required growth factors and nutrients. The proliferation and differentiation were studied and the influence of incorporation of the protein based growth factors and differentiation factors of the seeded cells on the scaffold were monitored.

Amphiphilic block copolymers have the tendency to self-assemble into micelles in a selective solvent because of the presence of both, hydrophilic as well as hydrophobic segments. These polymeric micelles consist of a core and shell like structure, in which the inner core is the hydrophobic part and can be utilized for encapsulation of drugs, whereas the hydrophilic block constituting the outer shell provides stabilization. The potential of polymeric micelles as drug carriers lie in their unique properties like small size, prolonged circulation, biodegradability and thermodynamic stability.

The present study developed a d-valerolactone based amphiphilic block copolymer to develop a novel micellar controlled delivery system for DOX and analysed its anticancer activity. The study involves the synthesis of a triblock copolymer of d-valerolactone, poly d-valerolactone)/poly(ethylene glycol)/poly(d-valerolactone) (VEV) by ring opening polymerization and characterization using IR, NMR and GPC. The thermal stability of VEV was analyzed using DTA and TGA. Micellization followed by biocompatibility studies of the copolymer were done to evaluate its potential as a carrier for drug delivery.

Fig 3. Sub-cellular internalization of DOX entrapped VEV micelles (VEVDMs)