Abstract
Treatment of tumor tissue without affecting normal cells has always been formidable task for drug delivery scientists and this task is effectively executed by polymer drug conjugate (PDC) delivery. The novelty of this concept lies in the utilization of a physical mechanism called enhanced permeability and retention (EPR) for targeting tumors. EPR is a physiological phenomenon that is customary for fast growing tumor and solves the problem of targeting the miscreant tissue. PDCs offer added advantages of reduced deleterious effects of anticancer drugs and augmentation of its formulation capability (e.g. Solubility). There are now at least eleven PDCs that have entered phase I/II/III clinical trial as anticancer drugs. PDCs once entered into the tumor tissue, taking advantage of EPR, are endocytosed into the cell either by simple or receptor mediated endocytosis. Various polymeric carriers have been used with hydrolyzable linker arm for conjugation with bioactive moiety. The hydrolyzable linkages of PDC are broken down by acid hydrolyses of lysosomes and releases the drug. High concentrations of the chemotherapeutic agent are maintained near the nucleus, the target site. Passive targeting by PDCs is due to the physiological event of EPR, which is becoming one of the major thrust areas for targeting solid tumors.
Keywords: EPR, polymer-drug conjugates, cancer, targeting, linkers, endocytosis, PEGylation, HPMA
Current Pharmaceutical Design
Title: Exploiting EPR in Polymer Drug Conjugate Delivery for Tumor Targeting
Volume: 12 Issue: 36
Author(s): Sweta Modi, Jay Prakash Jain, A. J. Domb and Neeraj Kumar
Affiliation:
Keywords: EPR, polymer-drug conjugates, cancer, targeting, linkers, endocytosis, PEGylation, HPMA
Abstract: Treatment of tumor tissue without affecting normal cells has always been formidable task for drug delivery scientists and this task is effectively executed by polymer drug conjugate (PDC) delivery. The novelty of this concept lies in the utilization of a physical mechanism called enhanced permeability and retention (EPR) for targeting tumors. EPR is a physiological phenomenon that is customary for fast growing tumor and solves the problem of targeting the miscreant tissue. PDCs offer added advantages of reduced deleterious effects of anticancer drugs and augmentation of its formulation capability (e.g. Solubility). There are now at least eleven PDCs that have entered phase I/II/III clinical trial as anticancer drugs. PDCs once entered into the tumor tissue, taking advantage of EPR, are endocytosed into the cell either by simple or receptor mediated endocytosis. Various polymeric carriers have been used with hydrolyzable linker arm for conjugation with bioactive moiety. The hydrolyzable linkages of PDC are broken down by acid hydrolyses of lysosomes and releases the drug. High concentrations of the chemotherapeutic agent are maintained near the nucleus, the target site. Passive targeting by PDCs is due to the physiological event of EPR, which is becoming one of the major thrust areas for targeting solid tumors.
Export Options
About this article
Cite this article as:
Modi Sweta, Prakash Jain Jay, Domb J. A. and Kumar Neeraj, Exploiting EPR in Polymer Drug Conjugate Delivery for Tumor Targeting, Current Pharmaceutical Design 2006; 12 (36) . https://dx.doi.org/10.2174/138161206779026272
DOI https://dx.doi.org/10.2174/138161206779026272 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Conditionally Replicating Adenoviruses for Cancer Treatment
Current Cancer Drug Targets Critical microRNAs in Lung Cancer: Recent Advances and Potential Applications
Anti-Cancer Agents in Medicinal Chemistry Anticancer Antifolates: Current Status and Future Directions
Current Pharmaceutical Design Integrin αvβ3 Antagonists for Anti-Angiogenic Cancer Treatment
Recent Patents on Anti-Cancer Drug Discovery The Potential Use of RNA-based Therapeutics for Breast Cancer Treatment
Current Medicinal Chemistry Second Generation Adeno-Associated Virus Type 2-based Gene Therapy Systems with the Potential for Preferential Integration into AAVS1
Current Gene Therapy Radionuclides Used in Nuclear Medicine Therapy – From Production to Dosimetry
Current Medical Imaging Poly(ADP-Ribose) Polymerase Inhibitors: New Pharmacological Functions and Potential Clinical Implications
Current Pharmaceutical Design Review: The JAK/STAT Protein Activation – Role in Cancer Development and Targeted Therapy
Current Signal Transduction Therapy A Systematic Analysis of Physicochemical and ADME Properties of All Small Molecule Kinase Inhibitors Approved by US FDA from January 2001 to October 2015
Current Medicinal Chemistry NF-κB Down–regulation and PARP Cleavage by novel 3-α-butyryloxy-β-boswellic Acid Results in Cancer Cell Specific Apoptosis and in vivo Tumor Regression
Anti-Cancer Agents in Medicinal Chemistry Inhibition of Tumor Angiogenesis by Antibodies, Synthetic Small Molecules and Natural Products
Current Medicinal Chemistry Accessing the Blood-Brain Barrier to Treat Brain Disorders
Current Nanomedicine A Review of Therapeutic Effects of Curcumin
Current Pharmaceutical Design Tailored Angiogenesis Inhibition in Cancer Therapy: Respecting the Heart to Improve the Net Outcome
Current Signal Transduction Therapy Frontotemporal Lobar Degeneration (FTLD): Review and Update for Clinical Neurologists
Current Alzheimer Research Undermining Tumor Angiogenesis by Gene Therapy: An Emerging Field
Current Gene Therapy Topoisomerase II Inhibitors and Poisons, and the Influence of Cell Cycle Checkpoints
Current Medicinal Chemistry Anticarcinogenic Actions of Tributyrin, A Butyric Acid Prodrug
Current Drug Targets Genetic Variants in Genes Involved in Mechanisms of Chemoresistance to Anticancer Drugs
Current Cancer Drug Targets