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PEGylation: a promising strategy to overcome challenges to cancer-targeted nanomedicines: a review of challenges to clinical transition and promising resolution

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Abstract

On account of heterogeneity, intrinsic ability of drug resistance, and the potential to invade to other parts of the body (malignancy), the development of a rational anticancer regimen is dynamically challenging. Chemotherapy is considered the gold standard for eradication of malignancy and mitigation of its reoccurrence; nevertheless, it has also been associated with detrimental effects to normal tissues owing to its nonselectivity and nominal penetration into the tumor tissues. In recent decades, nanotechnology-guided interventions have been well-acclaimed due to their ability to facilitate target-specific delivery of drugs, avoidance of nontarget distribution, alleviated systemic toxicity, and maximized drug internalization into cancer cells. Despite their numerous biomedical advantages, clinical translation of nanotechnology-mediated regimens is challenging due to their short plasma half-life and early clearance. PEGylation of nanomedicines has been adapted as an efficient strategy to extend plasma half-life and diminished early plasma clearance via alleviating the opsonization (uptake by monocytes and macrophages) of drug nanocarriers. PEGylation provides “stealth” properties to nanocarrier’s surfaces which diminished their recognition or uptake by cellular immune system, leading to longer circulation time, reduced dosage and frequency, and superior site-selective delivery of drugs. Therefore, this review aims to present a comprehensive overview of the pharmaceutical advantages and therapeutic feasibility of PEGylation of nanocarriers in improving tumor-specific targetability, reversing drug resistance, and improving pharmacokinetic profile of drugs and anticancer efficacy. Challenges to PEGylated cancer nanomedicines, possible adaptations to resolve those challenges, and pivotal requirement for interdisciplinary research for development of rational anticancer regimen have also been pondered.

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Acknowledgements

The authors would like to greatly acknowledge the Faculty of Pharmacy, Universiti Teknologi MARA (UiTM) Selangor, Malaysia, for their support in accomplishing this review project.

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Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM) Selangor, Puncak Alam Campus, 42300, Bandar Puncak Alam, Selangor, Malaysia

    Zahid Hussain

  2. Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, 2409 West University Avenue, PHR 4.116, Austin, TX, 78712, USA

    Shahzeb Khan

  3. HEJ, Research Institute of Chemistry, International Centre for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan

    Muhammad Imran

  4. Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, 22060, Pakistan

    Muhammad Sohail

  5. Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa

    Syed Wadood Ali Shah

  6. SEDA Pharmaceutical Development Services, the BioHub at Alderley Park, Cheshire, UK

    Marcel de Matas

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  1. Zahid Hussain
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  2. Shahzeb Khan
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Hussain, Z., Khan, S., Imran, M. et al. PEGylation: a promising strategy to overcome challenges to cancer-targeted nanomedicines: a review of challenges to clinical transition and promising resolution. Drug Deliv. and Transl. Res. 9, 721–734 (2019). https://doi.org/10.1007/s13346-019-00631-4

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