Kuldeep K. Bansal
Pharmaceutical Sciences, Laboratory, Faculty of Science and Engineering, Ã…bo Akademi University, Finland
Title: Novel polymers with functionalities from renewable feedstock for smart drug-delivery
Biography:
Dr. Kuldeep Bansal obtained his PhD in pharmacy discipline from the University of Nottingham in 2015 after receiving basic degree in pharmacy from India. As of 2017, he has been working in the lab of Prof. Rosenholm and has been developing novel polymers for drug delivery applications. His previous research mostly involved synthesis of polymers-based nanocarriers for enhancing safety, efficacy, and stability of drugs. His current bibliographic data includes 29 published papers, >700 citations and h-index 14 (Google Scholar 21.7.2022).
Abstract:
Polymer-drug conjugates with stimuli-sensitive linkers (smart polymer therapeutics) have demonstrated superior efficacy in targeted drug delivery. However, ongoing research is lacking in the simplicity of design and broad applicability of single polymeric material. Limited functional groups on polymers, tedious synthesis methodology, non-renewable monomer source, reproducibility, etc. are a few hurdles, which still need to be addressed to enhance the applicability of polymers in smart drug delivery. With the objective to circumvent these hurdles, we have recently reported the synthesis of a novel amphiphilic block copolymer (mPEG-b-PJL) using renewable jasmine lactone monomer under mild reaction conditions. The functional groups, such as -COOH, -NH2, -OH and aromatic ring were later introduced to the polymer via facile thiol-ene click reaction. As a proof of concept, doxorubicin (DOX) was conjugated to the hydroxyl terminated polymer [i.e., mPEG5k-b-PJL3k-(OH)24] via a disulfide linkage to generate PJL-DOX. It was expected that PJL-DOX release the higher drug in cancer cells due to the presence of excessive glutathione (a reductive agent). Further, the -COOH functional polymers were also analysed for their capability to increase the aqueous solubility of hydrophobic drugs by fabrication of polymeric micelles.
The PJL-DOX containing 30 wt% of DOX was readily self-assembled into micelles with an average hydrodynamic size of ~150 nm. The in-vitro cytotoxicity of PJL-DOX suggested redox triggered DOX release, while no significant toxicity was observed for polymer alone. In-vivo results suggested intermediate tumour inhibition activity of PJL-DOX compared to free DOX and marketed liposomal DOX formulation. However, the PJL-DOX demonstrate lesser side effects and increased mice survivability.
Further, the -COOH terminated polymer demonstrate high drug loading of weakly basic drugs, indicating that functional groups on polymer have a direct impact on loading in polymeric micelles. These polymers can be explored further to prepare nano-sized drug conjugates for targeted delivery, theranostics and/or combined delivery of bioactives. In addition, tuning of free functional groups can further enable their applications in polymeric micelles with high drug loading, which is otherwise hamper the clinical translation of micelles-based drug delivery system.