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Correspondence to Author: Dr. Sharadendu Bali, MBBS, MS, PhD. 

Professor, General Surgery, TMC& RC, TMU, Moradabad

DOI: 10.52338/tjoco.2025.5260

Abstract:

Cancer continues to be one of the leading causes of death worldwide, with 10 million fatalities and 19.3 million new cases reported in 2020. Multidrug resistance (MDR), a formidable issue in chemotherapy, is characterized by the ability of cancer cells to evade cytotoxic drugs through mechanisms such as altered drug targets, disrupted DNA repair, and overexpression of ATP-binding cassette (ABC) transporters like P-glycoprotein (P-gp, responsible for drug efflux). While older oral chemotherapeutics, including 5-fluorouracil (5-FU) and methotrexate, have been effective in certain cancers, their clinical applications are frequently limited by poor bioavailability, dose-limiting toxicities, and drug efflux associated with MDR. Recent evidence supports that incorporating old chemotherapeutic agents into nanocarrier systems such as solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and mesoporous silica nanoparticles can help overcome key barriers like low solubility, rapid metabolism, and P-gp–mediated efflux. Importantly, the co-delivery of these anti-mitotic drugs alongwith phytochemicals such as curcumin, resveratrol, and astragaloside IV can downregulate drug-efflux transporters, reverse both intrinsic and acquired resistance and increase the efficacy of the chemotherapeutic agents.
Among the nanocarrier systems, Lipid-based nanocarriers have demonstrated especial potential in overcoming MDR, including through codelivery. SLNs, for example, have been found to protect drugs from gastrointestinal degradation, facilitate controlled release, and improve oral absorption through lymphatic transport. NLCs, with their “imperfect” lipid matrix, permit higher drug loading and offer superior stability. These platforms have been successfully utilized to boost the bioavailability of agents such as doxorubicin, paclitaxel, and zerumbone. Polymeric micelles, liposomes, and dendrimers have been utilized to co-encapsulate both hydrophilic and hydrophobic compounds, providing additional versatility. This strategy of co-delivery using nanocarriers can be effective not just in disrupting efflux mechanisms and prolonging circulation time, but can also facilitate selective targeting of cancer cells by surface modification using ligands. This integrative approach holds significant potential to rejuvenate conventional drugs, and can make cancer treatment more convenient, potent, and patient-friendly

Keywords: Oral chemotherapy, Multidrug resistance (MDR), Phytochemicals, Nanoparticle co-delivery, potentiating older drugs.

Citation:

Dr. Sharadendu Bali, Breathing New Life into Conventional Chemotherapy drugs: Enhancing Efficacy via Nanoparticle Codelivery along with Phytochemicals. The Journal of Clinical Oncology 2025.