Abstract
The blood-brain barrier (BBB) represents a large obstacle for the treatment of central nervous system diseases. Targeting endogenous nutrient transporters that transcytose the BBB is one promising approach to selectively and noninvasively deliver a drug payload to the brain. The main limitations of the currently employed transcytosing receptors are their ubiquitous expression in the peripheral vasculature and the inherent low levels of transcytosis mediated by such systems. In this review, approaches designed to increase the repertoire of transcytosing receptors which can be targeted for the purpose of drug delivery are discussed. In particular, combinatorial protein libraries can be screened on BBB cells in vitro or in vivo to isolate targeting peptides or antibodies that can trigger transcytosis. Once these targeting reagents are discovered, the cognate BBB transcytosis system can be identified using techniques such as expression cloning or immunoprecipitation coupled with mass spectrometry. Continued technological advances in BBB genomics and proteomics, membrane protein manipulation, and in vitro BBB technology promise to further advance the capability to identify and optimize peptides and antibodies capable of mediating drug transport across the BBB.
Keywords: Blood-brain barrier, receptor-mediated transport, brain drug delivery.
Current Pharmaceutical Design
Title:Combinatorial Approaches for the Identification of Brain Drug Delivery Targets
Volume: 20 Issue: 10
Author(s): Charles C. Stutz, Xiaobin Zhang and Eric V. Shusta
Affiliation:
Keywords: Blood-brain barrier, receptor-mediated transport, brain drug delivery.
Abstract: The blood-brain barrier (BBB) represents a large obstacle for the treatment of central nervous system diseases. Targeting endogenous nutrient transporters that transcytose the BBB is one promising approach to selectively and noninvasively deliver a drug payload to the brain. The main limitations of the currently employed transcytosing receptors are their ubiquitous expression in the peripheral vasculature and the inherent low levels of transcytosis mediated by such systems. In this review, approaches designed to increase the repertoire of transcytosing receptors which can be targeted for the purpose of drug delivery are discussed. In particular, combinatorial protein libraries can be screened on BBB cells in vitro or in vivo to isolate targeting peptides or antibodies that can trigger transcytosis. Once these targeting reagents are discovered, the cognate BBB transcytosis system can be identified using techniques such as expression cloning or immunoprecipitation coupled with mass spectrometry. Continued technological advances in BBB genomics and proteomics, membrane protein manipulation, and in vitro BBB technology promise to further advance the capability to identify and optimize peptides and antibodies capable of mediating drug transport across the BBB.
Export Options
About this article
Cite this article as:
Stutz C. Charles, Zhang Xiaobin and Shusta V. Eric, Combinatorial Approaches for the Identification of Brain Drug Delivery Targets, Current Pharmaceutical Design 2014; 20 (10) . https://dx.doi.org/10.2174/13816128113199990459
DOI https://dx.doi.org/10.2174/13816128113199990459 |
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
-
Heterocyclic Drug-polymer Conjugates for Cancer Targeted Drug Delivery
Anti-Cancer Agents in Medicinal Chemistry Apoptosis Pathways and Neuroblastoma Therapy
Current Pharmaceutical Design Immunologic Diseases and Brain Tumors
Inflammation & Allergy - Drug Targets (Discontinued) The Effect of Chemotherapy/Radiotherapy on Cancerous Pattern Recognition by NK Cells
Current Medicinal Chemistry Phenolic Compounds as Nutraceuticals or Functional Food Ingredients
Current Pharmaceutical Design Induction of Antitumor Immune Responses with Recombinant Lentivector: Role of Skin Derived DCs
Current Cancer Therapy Reviews Prophylactic Admission of an In Vitro Reconstructed Complexes of Human Recombinant Heat Shock Proteins and Melanoma Antigenic Peptides Activates Anti-Melanoma Responses in Mice
Current Molecular Medicine Deglucohellebrin: A Potent Agent for Glioblastoma Treatment
Anti-Cancer Agents in Medicinal Chemistry The Crosstalk of RAS with the TGF-β Family During Carcinoma Progression and its Implications for Targeted Cancer Therapy
Current Cancer Drug Targets Peroxisome Proliferator-Activated Receptors: Role of Isoform Gamma in the Antineoplastic Effect of Iodine in Mammary Cancer
Current Cancer Drug Targets Implications of PEGylation of Carbon Nanotubes for Central Nervous System Bioavailability
CNS & Neurological Disorders - Drug Targets Natural and Engineered Cystine Knot Miniproteins for Diagnostic and Therapeutic Applications
Current Pharmaceutical Design Antigenic Differences Between Normal and Malignant Cells as a Basis for Treatment of Intracerebral Neoplasms Using a DNA-Based Vaccine
Current Genomics Apoptosis is a Critical Cellular Event in Cancer Chemoprevention and Chemotherapy by Selenium Compounds
Current Cancer Drug Targets Synergistic Interplay of Medicinal Chemistry and Formulation Strategies in Nanotechnology – From Drug Discovery to Nanocarrier Design and Development
Current Topics in Medicinal Chemistry Physiology and Pathophysiology of Na+/H+ Exchange Isoform 1 in the Central Nervous System
Current Neurovascular Research Non-Coding RNA in Brain Development and Disorder
Current Medicinal Chemistry The Recent Progresses on The Improved Therapy of Melanoma by Novel Drug Delivery Systems
Current Drug Targets Editorial [Hot Topic: Targeted Alpha Therapy – Part II (Guest Editor: Jorgen Elgqvist)]
Current Radiopharmaceuticals Recent Progress in Discovery and Development of Antimitotic Agents
Anti-Cancer Agents in Medicinal Chemistry