Abstract
A large number of liposome-based non-viral gene and siRNA delivery systems include monovalent cholesteryl cytofectins with acyclic head groups in their formulations. Progress in their clinical development has, however, been hampered by relatively low transfection efficiencies. Structural differences between members of this class of cationic amphiphiles are located primarily in their linker, spacer and head group regions. This review examines the structural diversity encountered in each of these domains and seeks to identify those features linked to favourable transfection activity. Thus the ether linker, with its greater chemical and metabolic stability, is associated with higher transfection activity than ester, amide or carbamoyl tethers. While a medium length 6 atom spacer in the ether series is preferred over shorter spacers for enhanced activity, short (2 atom) to long (11 atom) spacers are effective in the more common carbamoyl series. For largely historic reasons, the dimethylamino head group has remained a popular cationic centre, but several studies have shown that the N-hydroxyethyl secondary amine functionality may be more effective in cytofectins. This observation has been attributed, in part, to the increased hydrophilicity of the head group and facilitated release of the nucleic acid cargo from liposomes in endosomal compartments. However, the hypothesis that the incorporation of each of these favourable chemical features into a single novel cytofectin may lead to superior transfection activity remains to be fully tested.
Keywords: Cholesterol, cytofectin, gene delivery, liposomes, monovalent, review.
Current Pharmaceutical Biotechnology
Title:Liposomal Formulation of Monovalent Cholesteryl Cytofectins with Acyclic Head Groups and Gene Delivery: A Systematic Review
Volume: 16 Issue: 10
Author(s): Mario Ariatti
Affiliation:
Keywords: Cholesterol, cytofectin, gene delivery, liposomes, monovalent, review.
Abstract: A large number of liposome-based non-viral gene and siRNA delivery systems include monovalent cholesteryl cytofectins with acyclic head groups in their formulations. Progress in their clinical development has, however, been hampered by relatively low transfection efficiencies. Structural differences between members of this class of cationic amphiphiles are located primarily in their linker, spacer and head group regions. This review examines the structural diversity encountered in each of these domains and seeks to identify those features linked to favourable transfection activity. Thus the ether linker, with its greater chemical and metabolic stability, is associated with higher transfection activity than ester, amide or carbamoyl tethers. While a medium length 6 atom spacer in the ether series is preferred over shorter spacers for enhanced activity, short (2 atom) to long (11 atom) spacers are effective in the more common carbamoyl series. For largely historic reasons, the dimethylamino head group has remained a popular cationic centre, but several studies have shown that the N-hydroxyethyl secondary amine functionality may be more effective in cytofectins. This observation has been attributed, in part, to the increased hydrophilicity of the head group and facilitated release of the nucleic acid cargo from liposomes in endosomal compartments. However, the hypothesis that the incorporation of each of these favourable chemical features into a single novel cytofectin may lead to superior transfection activity remains to be fully tested.
Export Options
About this article
Cite this article as:
Ariatti Mario, Liposomal Formulation of Monovalent Cholesteryl Cytofectins with Acyclic Head Groups and Gene Delivery: A Systematic Review, Current Pharmaceutical Biotechnology 2015; 16 (10) . https://dx.doi.org/10.2174/1389201016666150629103059
DOI https://dx.doi.org/10.2174/1389201016666150629103059 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
Call for Papers in Thematic Issues
Artificial Intelligence in Bioinformatics
Bioinformatics is an interdisciplinary field that analyzes and explores biological data. This field combines biology and information system. Artificial Intelligence (AI) has attracted great attention as it tries to replicate human intelligence. It has become common technology for analyzing and solving complex data and problems and encompasses sub-fields of machine ...read more
Latest Advancements in Biotherapeutics
The scope of this thematic issue is to comprehensively explore the rapidly evolving landscape of biotherapeutics, emphasizing breakthroughs in precision medicine. Encompassing diverse therapeutic modalities, the issue will delve into the latest developments in monoclonal antibodies, CRISPR/Cas gene editing, CAR-T cell therapies, and innovative drug delivery systems, such as nanoparticle-based ...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
Related Articles
-
Editorial: (Thematic Issue: Occupational Exposure: An Undermined Risk Factor of Lung Diseases in the Informal Sectors of Developing Economy)
Current Respiratory Medicine Reviews Roles of NHERF1/EBP50 in Cancer
Current Molecular Medicine Development of NGR-Based Anti-Cancer Agents for Targeted Therapeutics and Imaging
Anti-Cancer Agents in Medicinal Chemistry Targeted – Therapy and Imaging Response: A New Paradigm For Clinical Evaluation?
Reviews on Recent Clinical Trials Cyclin-Dependent Kinase as a Novel Therapeutic Target: An Endless Story
Current Chemical Biology Targeting CREB for Cancer Therapy: Friend or Foe
Current Cancer Drug Targets Oxidative Phosphorylation as a Target to Arrest Malignant Neoplasias
Current Medicinal Chemistry The Biological Role of mTOR in the Pathogenesis of Solid Tumors: An Overview
Current Enzyme Inhibition Epigenetics of Virus-Induced Tumors: Perspectives for Therapeutic Targeting
Current Pharmaceutical Design Mutations of Chromatin Structure Regulating Genes in Human Malignancies
Current Protein & Peptide Science Pemetrexed – First-Line Therapy for Non-Squamous Non-Small Cell Lung Cancer: A Review of Patent Literature
Recent Patents on Anti-Cancer Drug Discovery Safety of Nanoparticles in Medicine
Current Drug Targets HtrA Protease Family as Therapeutic Targets
Current Pharmaceutical Design Recent Advances in Classical and Non-Classical Antifolates as Antitumor and Antiopportunistic Infection Agents: Part I
Anti-Cancer Agents in Medicinal Chemistry Role of α7-Nicotinic Acetylcholine Receptor in Normal and Cancer Stem Cells
Current Drug Targets Lactate Transporters and pH Regulation: Potential Therapeutic Targets in Glioblastomas
Current Cancer Drug Targets NGR-based Strategies for Targeting Delivery of Chemotherapeutics to Tumor Vasculature
Anti-Cancer Agents in Medicinal Chemistry Pharmacophore Modeling and 3D QSAR Studies of Novel Human Carbonic Anhydrase IX Inhibitors
Letters in Drug Design & Discovery Anticancer Therapeutic Strategies Based on CDK Inhibitors
Current Pharmaceutical Design Membrane Permeable Lipophilic Cations as Mitochondrial Directing Groups
Current Topics in Medicinal Chemistry