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