Research Projects

A novel ionic liquid composite (AAIL) has been developed through a green metathesis reaction involving choline hydroxide, the antiplatelet drug aspirin (ASP), and the redox-sensitive drug ascorbic acid (AA). The reaction's progression and product formation were monitored using pH changes, conductivity measurement, and IR spectroscopy. AAIL was subsequently employed to dissolve paclitaxel (PTX) in water via a single-pot, in-situ technique (AAIL-PTX). PTX stability in the ionic liquid dispersion was confirmed through HPLC analysis. Light scattering experiments indicated supramolecular aggregate formation in water by the composite, with particle sizing revealing multiple entities around 5 nm. Encouragingly, this in-situ ionic liquid-based solubilization method for PTX eliminates the need for cremophor EL—a solubilizing agent in the marketed PTX formulation (Taxol®)—which is associated with severe hypersensitivity reactions and exacerbated neuropathy. This project aims to optimize AAIL-PTX and subject it to comprehensive physicochemical characterization. Studies will include dilution stability (as a surrogate for injectability), dissolution testing, assay, electron microscopy, small-angle X-ray scattering (SAXS), protocol-bound stability testing, and temperature cycling. These analyses will determine the physical and chemical status of PTX, ASP, and AA within AAIL-PTX. Additionally, to explore whether AAIL contributes novel anticancer mechanisms through the antiplatelet and redox-sensitive actions of ASP and AA, AAIL-PTX will undergo comparative in vitro cell culture assays. These assays will measure IC50, apoptosis, reactive oxygen species (ROS) levels, Ki-67 expression in cancer cells co-cultured with treated platelets, cancer cell stemness (via Aldefluor assay), Matrigel invasion, haemolytic potential, myelosuppression, and allergic response via complement activation. To evaluate safety and address the hypersensitivity and allergic reactions associated with Taxol®, in vivo studies will include non-immune anaphylaxis and complement activation-related pseudo-allergy investigations in guinea pigs. Single-dose acute toxicity studies in mice will assess cardiac parameters, serum liver markers, and blood cell counts as indicators of relative safety. Further, a syngeneic mouse model of breast cancer will compare the anticancer efficacy of AAIL-PTX, AAIL, and Taxol® at equivalent PTX doses. Pharmacokinetic studies will explore the impact of incorporating PTX into the ionic liquid versus Taxol®. Using a validated LC-MS method, these studies will measure pharmacokinetic differences following intravenous dosing in rats. Overall, the project seeks to leverage platelet dysfunction and redox imbalance pathways prevalent in cancers, through a novel aspirin-ascorbic acid ionic liquid composite. By enhancing paclitaxel’s anticancer activity and reducing hypersensitivity risks, AAIL-PTX could offer a safer and more effective alternative to existing formulations.