Polymer-based Nanostructures

Dr Pavel Broz MD is at the University Hospital Basel, Switzerland.

• 1 - Foreword;2 - Basics;Polymer materials for biomedical application;Factors influencing the polymer's applicability in biomedical fields;References;Contact;Strategies for transmembrane passage of polymer-based nanostructures;Introduction;Peptides and proteins delivery;Gene delivery;General vaccines delivery;Nanoparticles;Strategies for Transmembrane Passage of Polymer-Based Nanostructures;Gastrointestinal Transepithelial Permeability of Polymer-Based Nanostructures;Mechanisms of Transepithelial Transport of Nanoparticles;Paracellular Pathway;Transcellular Pathway;Strategies for Transepithelial Permeability of Polymer-Based Nanostructures through the Paracellular Pathway;Strategies for Transepithelial Permeability of Polymer-Based Nanostructures through the Transcellular Pathway;Modification of Polymer-Based Nanostructure Surfaces with Targeting Moieties (Targeted Delivery Systems);Gastrointestinal Targeting of Nanoparticles with Surfaces Modified by Lectins;M Cell Targeting with Polymer-Based Nanostructures Decorated With Lectins on the Surface;Capability of M cells to absorb non-targeted nanoparticles;Strategies for the absorption of targeted nanoparticles by M cells;The use of lectins to target M cells for particulate uptake;The use of Invasins to target M cells for particulate uptake;M Cell Targeting with Polymer-Based Nanostructures Decorated With Antibody on the Surface;Strategy Based on the Understanding and the Use of the right animal model and Conversion of Epithelia cells to M cells;Enterocyte Targeting with Polymer-Based Nanostructures Decorated With Lectins on the Surface;The Use of targeted lecitin-decorated particles to promote particulate absorption by the enterocytes;The Use of targeted Vitamin B12-decorated particles to promote particulate absorption by the enterocytes;The Use of targeted RGD peptide-decorated particles to promote particulate absorption by the enterocytes;Colon Targeting with Polymer-Based Nanostructures Decorated With Lectins on the Surface;Strategies for Gastrointestinal Delivery of Nanoparticles Using Bio-(Muco-) adhesion mechanism;Bioadhesion and Mucoadhesion;Bioadhesion of Polymer-Based Nanostructures;Mucoadhesion Based on Non-specific Interactions;Bioadhesion Based on Specific Interactions;Bio-(muco) adhesive nanoparticles;Chitosan;Poly(lactide-co-glycolide) copolymer;Poly(methylvinylether-co-maleic anhydride) (PVM/MA);Poly(alkylcyanoacrylate);Poly-fumaric anhydride-co-sebacic anhydride (P(FA:SA));Methacrylic acid grafted with poly(ethylene glycol), and acrylic acid grafted with poly(ethylene glycol);Hydroxypropyl- -cyclodextrin-insulin (HP CD-I) complex encapsulated polymethacrylic acid-chitosan-polyether (polyethylene glycol-polypropylene glycol copolymer) (PMCP) nanoparticles;Ply(N-isopropylacrylamide) (PNIPAAm) hydrogel nanoparticles;The Use Permeability Or Absorption Enhancers as a Strategy for Transepithelial Permeability of Nanoparticles;Surfactants;Chitosan and its derivatives;Thiolated polymers;Strategy based on the Influence of Particle Size on Transepithelial Permeability of Nanoparticles;Nanoparticle Size and Vaccine Development;Strategies Based on the Influence of Particle Surface Properties (Charge and hydrophobicity) on Transepithelial Permeability of Nanoparticles;Strategies Based on Protein Transduction;Historical Perspectives;Cell-penetrating peptides (CPPs) involved in delivery of therapeutic agents;Mechanism of Translocation;Applications of CPP to Particulate Permeability;Strategy for Permeability of Nanostructures Across Other Mucosal Epithelia;Transepithelial permeability of polymer-based nanostructures across the lung epithelium;Effect of Particle Size;Mucoadhesion;Targeting with Lectin;Nasal route;Ophthalmic route;Size;Mucoadhesion;Surface Charge;Strategies for Permeability of Polymer-Based;Nanostructures Across Blood-Brain Barrier;Surfactant;Surface charge;Particle size;Antibody for targeting the Blood-Brain Barrier;Lectin for targeting the Blood-Brain Barrier;Nanogel for targeted delivery of drugs and macromolecules to the brain;References;Contact;Nanoparticle Engineering for the Lymphatic System and Lymph Node Targeting;Introduction;Nanoparticle size;Nanoparticle surface engineering;Surface modification with serum;Surface manipulation with block copolymers;Recent trends in vesicular surface engineering;Platform nanotechnologies;Conclusions;References;Contact;Strategies for Intracellular Delivery of Polymer-based Nanosystems;Introduction;Barriers to cellular transport of nanosystems;Nanosystem-cell interactions and cellular internalization;Intracellular trafficking of nanosystems;Challenges;References;Contact;Strategies for triggered release from polymer-based nanostructures;Introduction;Stimuli applied for triggered release;Temperature;Polymers based on LCST;Polymers based on amphiphilic balance;Polymeric nanovehicles for drug delivery with temperature-triggered release mechanism;pH;Anionic and cationic polymers;Polymeric systems with acidic pH-cleavable bonds;Polymeric nanovehicles for drug release by pH-triggered destabilization mechanism;Other stimuli (light, electric fields, ionic strength, biomolecules, etc.);Magnetic and electric field;Ultrasound;Light;Specific interactions;Channel proteins - candidates for triggers of drug release;Antigen responsive polymers;Enzyme-triggered drug delivery systems;Glucose-responsive polymers;Redox-sensitive systems;References;Contact;Strategies for enhanced biocompatibility and biodegrability of polymer-based nanostructures;3 - Polymer-based nanostructures for diagnostic applications;Polymeric nanoparticles for medical imaging;Introduction;Polymeric particles in medical imaging;MRI Contrast agents;Overview;Toward ideal contrast agents;The case for nanoparticle agents: Gd-albumin experience;The problem of MRI sensitivity;References;Type I, Linear chains, polylysine backbone;Motivation;Synthesis and Conformation;Role of electric dipole centers on the polymer chain;Transport rate blocking;cRGD peptide effects;Binding site density;Scaling law;Trans-endothelial transport: the new mechanism;Cell-surface assisted migration;Summary;Tumor assessment;References;Type I, linear chains, dextran backbone;Motivation and early results;DOTA linked dextran;Synthesis of carboxymethyldextran -A2-Gd-DOTA;Clearance and safety;Angiography;Tumor assessment;New DTPA-dextran constructs;Dextran constructs for nuclear and optical imaging;Summary;References;Type II, Dendrimers and globular particles;Introduction;Structures and synthesis of principle classes of dendrimers for imaging;DTPA-dendrimers, principle characteristics;DOTA linked dendrimer, Gadomer 17;Structure and characteristics;Biodistribution and elimination;Dendrimer elimination and safety;Remarks on safety;Applications;Angiography;Lymph node evaluation;Tumor characterization;Summary;Other constructs, targeting, and CT;References;Globular agents and endothelial pore size distribution;Tumor endothelial leakiness, large pore dominance model;Theoretical;Pore size distribution in rat mammary tumors;PEG linked Gd-DTPA-polylysine;References;Iron oxide nanoparticles;Summary overview;Developments;Polymer coating;Monomer coating;Labeling of cells;Cell trafficking;Cell labeling II and detection limits;Lymphocyte homing;Single cell detection;Signal nonlinearity;Lymphography;Gene expression;Targeting;Tumor assessment;References;Contact;Polymeric vesicles/capsules for diagnostic applications in medicine;Introduction;Ex vivo Diagnostics;Polymeric Nanoparticles;Diagnostic Imaging;X-Ray;Liposomes;Polymeric particles;Gold particles;Magnetic Resonance Imaging-contrast;SPIOs and USPIOs;Liposomes;Dendrimers;Ultrasound Contrast Agents;Surfactant-stabilized nanobubbles;Liquid Perfluorocarbons;Solid nanoparticles;Hollow Polymeric nanocapsules;Imaging and Drug and Gene delivery;Targeted UCA;Gold nanoparticles and photoacoustic measurements;Optical Imaging;Radionuclide imaging;Single photon emission computed tomography;Positron emission tomography;Conclusion;References;Contact;4 - Polymer-based nanostructures for therapeutic applications;Polymeric micelles for therapeutic applications in medicine;Introduction;Solubilization by micelles;Polymeric micelles;Micelle preparation, morphology, and drug loading;Drug-loaded polymeric micelles in vivo;targeted and stimuli-sensitive micelles;Other applications of polymeric micelles;Micelles in immunology;Micelles as carriers of contrast agents;Conclusion;References;Contact;Polymeric particles for therapeutic applications in medicine;Anti-Cancer Polymersomes;Introduction;Polymersome structure and properties;Controlled release polymersomes;Small molecule chemotherapeutics for shrinking tumors;Efforts to target polymersomes;Conclusions and opportune comparisons to copolymer micelles;References;Contact;5 - Polymer-based nanostructures with an intelligent functionality;Polymer-based nanoreactors for medical applications;Introduction;The nanoreactor toolbox;Polymers;Channels and enzymes used in nanoreactors;Permeabilizing proteins;Encapsulated proteins;Preparation methods;Ethanol method;Film hydration method;Direct dispersion method;Functionalized reactors;Targeting of nanoreactors to different tissues;Controlling the activity of the nanoreactor;Applications;Open questions;References;Contact;Nanoparticles for cancer diagnosis and therapy;Introduction;Cancer facts/problems;Nanoparticle advantages for cancer therapy and imaging;Nanoparticles for therapy;Chemotherapy;Polymeric nanoparticles;Dendrimer;Solid lipid nanoparticles (SLN);Low density lipoprotein (LDL);Radiotherapy;Photodynamic Therapy (PDT);Thermotherapy;Nanoparticles for imaging;Magnetic resonance imaging (MRI);Optical Imaging;X-ray Computed Tomography (CT);Bimodal Imaging: MRI and Fluorescence Imaging;Multitasking nanoparticles for integrated imaging and therapy;Summary and future challenges;Acknowledgements;References;Contact