Combination Therapy Using Phytochemicals and PARP Inhibitors in Hybrid Nanocarriers: An Optimistic Approach for the
Mohammad Javed Qureshi1, Gurpreet Kaur Narde1, Alka Ahuja1
1Department of Pharmaceutics, College of Pharmacy, National University of Science and Technology, P.O. Box 620, Muscat PC130, Oman.
Abstract:
DNA damage repair is a hallmark of any cancer growth, eventually leading to drug resistance and death. The poly ADP-ribose polymerase (PARP) enzyme is vital in repairing damaged DNA in normal and cancer cells with mutated DNA damage response (DDR) genes. Inhibitors of the PARP enzyme aid in chemotherapy, as shown by drug combinations such as Olaparib and Irinotecan in breast cancer treatment. However, the effect of Olaparib in colon cancer has not been studied extensively. Synthetic drugs have a significant limitation in cancer treatment due to drug resistance, leading to colon cancer relapse. Bioavailability of Olaparib and other PARP inhibitors is limited due to their hydrophobicity, which poses a significant challenge. These limitations and challenges can be addressed by encapsulating Olaparib in nanoparticles that could possibly increase the bioavailability of the drug at the site of action. New age nanoparticles, such as hybrid nanoparticles, provide superior quality in terms of design and circulatory time of the drug in the plasma. The side effects of Olaparib as a chemotherapeutic pave the way for exploring phytochemicals that may have similar effects. The combined impact of Olaparib and phytochemicals such as genistein, resveratrol and others in nano-encapsulated form can be explored in the treatment of colon cancer.
Insights
Poly (ADP-ribose) polymerase (PARP) inhibitors like Olaparib show promise for colon cancer. Encapsulating Olaparib in nanoparticles may improve its effectiveness and bioavailability, potentially overcoming drug resistance.
Area of Science:
- Oncology
- Pharmacology
- Nanotechnology
Background:
- DNA damage repair is crucial for cancer growth and drug resistance.
- Poly (ADP-ribose) polymerase (PARP) enzymes are key in DNA repair, especially in cancers with DNA damage response (DDR) gene mutations.
- PARP inhibitors, like Olaparib, are used in chemotherapy but have limitations in colon cancer treatment.
Purpose of the Study:
- To investigate the potential of Olaparib, a PARP inhibitor, in colon cancer treatment.
- To address the limited bioavailability and hydrophobicity challenges of Olaparib through nanoparticle encapsulation.
- To explore the synergistic effects of nano-encapsulated Olaparib with phytochemicals for enhanced colon cancer therapy.
Main Methods:
- Review of existing literature on PARP inhibitors, colon cancer, drug delivery systems, and phytochemicals.
- Conceptual exploration of nanoparticle encapsulation strategies for hydrophobic drugs like Olaparib.
- Analysis of potential benefits of hybrid nanoparticles for improved drug circulation and targeted delivery.
- Consideration of phytochemicals (e.g., genistein, resveratrol) as adjuncts to Olaparib therapy.
Main Results:
- Olaparib's efficacy in colon cancer requires further extensive study.
- Hydrophobicity limits the bioavailability of Olaparib and other PARP inhibitors.
- Nanoparticle encapsulation, particularly with hybrid nanoparticles, offers a potential solution to enhance drug bioavailability and circulation time.
- Phytochemicals present a potential alternative or adjunct therapy due to their own anti-cancer properties and fewer side effects.
Conclusions:
- Nano-encapsulation of Olaparib could overcome bioavailability limitations and improve its efficacy in colon cancer.
- Combining nano-encapsulated Olaparib with phytochemicals presents a promising strategy for overcoming drug resistance and treating colon cancer.
- Further research is warranted to explore the therapeutic potential of this combined nano-formulation approach.
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