Mucus Penetrating Nanoparticles: Biophysical Tool And Method Of Drug And Gene Delivery.
Laura M Ensign, C. Schneider, J. Suk, R. Cone, J. Hanes
Published 2012 · Medicine, Materials Science
Download PDFAnalyze on Scholarcy
A method that could provide more uniform and longer-lasting drug and gene delivery to mucosal surfaces holds the potential to greatly improve the effectiveness of prophylactic and therapeutic approaches for numerous diseases and conditions, including sexually transmitted infections, cystic fibrosis, chronic rhinosinusitis, inflammatory bowel disease, and glaucoma to name a few. However, the body's natural defenses, including adhesive, rapidly cleared mucus linings coating nearly all entry points to the body not covered by skin, has limited the effectiveness of drug and gene delivery by nanoscale delivery systems. This article discusses the recent development of the “mucuspenetrating particle” or “MPP” nanotechnology, and how it has been used to both enhance understanding of the nanoscale barrier properties of human mucus secretions, and to achieve more uniform and longer-lasting drug delivery to mucosal tissues following topical administration. Drug loaded MPPs possess non-adhesive coatings that allow them to rapidly penetrate mucus layers through openings in the mucus mesh at rates nearly as fast as they would penetrate pure water. Critically, MPPs allow enhanced drug and gene delivery to mucosal tissues without diminishing the protective function of mucus. Recent progress in the development of MPPs as a biophysical tool to probe the length-scale dependent rheological properties of mucosal secretions and as a method for drug and gene delivery is highlighted.
This paper references
Mucins, mucus, and sputum.
Judith A. Voynow (2009)
Nanoparticles reveal that human cervicovaginal mucus is riddled with pores larger than viruses
S. Lai (2009)
Pluronic-based cationic block copolymer for forming pDNA polyplexes with enhanced cellular uptake and improved transfection efficiency.
Tsz Chung Lai (2011)
Variances in mucus architecture as a cause of cervical factor infertility.
W. W. Poon (1985)
Mucoadhesion of poly(2-hydroxyethyl methacrylate) is improved when linear poly(ethylene oxide) chains are added to the polymer network
A. D. Ascentiis (1995)
An Obstruction-Scaling Model for Diffusion in Homogeneous Hydrogels
B. Amsden (1999)
Human cervical mucus and its interaction with sperm: a fine-structural view.
A. I. Yudin (1989)
Gene transfer to the lung: lessons learned from more than 2 decades of CF gene therapy.
U. Griesenbach (2009)
The penetration of fresh undiluted sputum expectorated by cystic fibrosis patients by non-adhesive polymer nanoparticles.
J. Suk (2009)
Ocular Delivery of Compacted DNA-Nanoparticles Does Not Elicit Toxicity in the Mouse Retina
Xi-Qin Ding (2009)
A poly(ethylene glycol)-based surfactant for formulation of drug-loaded mucus penetrating particles.
Olcay Mert (2012)
Non-degradative intracellular trafficking of highly compacted polymeric DNA nanoparticles.
A. J. Kim (2012)
Controlled Delivery Systems for Proteins Based on Poly(Lactic/Glycolic Acid) Microspheres
S. Cohen (2004)
Altering Mucus Rheology to “Solidify” Human Mucus at the Nanoscale
S. Lai (2009)
Direct Measurement of Interactions between Tethered Poly(ethylene glycol) Chains and Adsorbed Mucin Layers
N. Efremova (2002)
Solute Diffusion within Hydrogels. Mechanisms and Models
B. Amsden (1998)
Real-time multiple-particle tracking: applications to drug and gene delivery.
Junghae Suh (2005)
Transfection of airway epithelium by stable PEGylated poly-L-lysine DNA nanoparticles in vivo.
A. Ziady (2003)
Novel approaches to vaginal delivery and safety of microbicides: biopharmaceuticals, nanoparticles, and vaccines.
K. Whaley (2010)
Enhanced Viscoelasticity of Human Cystic Fibrotic Sputum Correlates with Increasing Microheterogeneity in Particle Transport*
M. Dawson (2003)
Surface modifications and molecular imprinting of polymers in medical and pharmaceutical applications.
Petr Bureš (2001)
Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues.
S. Lai (2009)
Drug carrier nanoparticles that penetrate human chronic rhinosinusitis mucus.
S. Lai (2011)
Why consider vaginal drug administration?
N. Alexander (2004)
Biodegradable nanoparticles composed entirely of safe materials that rapidly penetrate human mucus.
Ming Yang (2011)
Pegylated GL67 lipoplexes retain their gene transfection activity after exposure to components of CF mucus
NN Sanders (2002)
Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus
S. Lai (2007)
Uptake and release of budesonide from mucoadhesive, pH-sensitive copolymers and their application to nasal delivery.
K. Nakamura (1999)
Extracellular barriers in respiratory gene therapy☆
N. Sanders (2009)
Microbicide Efficacy and Toxicity Tests in a Mouse Model for Vaginal Transmission of Chlamydia trachomatis
S. Achilles (2002)
Common Gene Therapy Viral Vectors Do Not Efficiently Penetrate Sputum from Cystic Fibrosis Patients
Kaoru Hida (2011)
Ultrastructure of the human periovulatory cervical mucus.
Francisco Ceric (2005)
Barrier properties of mucus.
Richard A. Cone (2009)
Comparative Uptake Studies of Bioadhesive and Non-Bioadhesive Nanoparticles in Human Intestinal Cell Lines and Rats: The Effect of Mucus on Particle Adsorption and Transport
I. Behrens (2004)
Molecular aspects of muco- and bioadhesion: tethered structures and site-specific surfaces.
Y. Huang (2000)
Long-term transgene expression in the central nervous system using DNA nanoparticles.
D. Yurek (2009)
Particle Tracking Microrheology of Complex Fluids
T. Mason (1997)
Biodegradable mucus-penetrating nanoparticles composed of diblock copolymers of polyethylene glycol and poly(lactic-co-glycolic acid)
T. Yu (2011)
Antibody diffusion in human cervical mucus.
W. Saltzman (1994)
Diffusion of macromolecules and virus-like particles in human cervical mucus.
S. S. Olmsted (2001)
Human Immunodeficiency Virus Type 1 Is Trapped by Acidic but Not by Neutralized Human Cervicovaginal Mucus
S. Lai (2009)
Rapid transport of muco-inert nanoparticles in cystic fibrosis sputum treated with N-acetyl cysteine.
J. Suk (2011)
Transport of metal oxide nanoparticles and single-walled carbon nanotubes in human mucus
A. Jachak (2012)
Polyanhydrides: an overview.
N. Kumar (2002)
MUC1 cell surface mucin is a critical element of the mucosal barrier to infection.
J. L. McAuley (2007)
Highly compacted DNA nanoparticles with low MW PEG coatings: in vitro, ex vivo and in vivo evaluation.
Nicholas J. Boylan (2012)
N-acetylcysteine Enhances Cystic Fibrosis Sputum Penetration and Airway Gene Transfer by Highly Compacted DNA Nanoparticles.
J. Suk (2011)
Mucoadhesive Nanoparticles May Disrupt the Protective Human Mucus Barrier by Altering Its Microstructure
Y. Wang (2011)
Optical measurements of frequency-dependent linear viscoelastic moduli of complex fluids.
Addressing the PEG mucoadhesivity paradox to engineer nanoparticles that "slip" through the human mucus barrier.
Y. Wang (2008)
Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier
Benjamin C Tang (2009)
Micro- and macrorheology of mucus.
S. Lai (2009)
Nanoparticles as protein and gene carriers to mucosal surfaces.
M. de la Fuente (2008)
Evidence for airway surface dehydration as the initiating event in CF airway disease
R. Boucher (2007)
This paper is referenced by
Mammalian gastrointestinal tract parameters modulating the integrity, surface properties, and absorption of food‐relevant nanomaterials
Susann Bellmann (2015)
Influences of nanomaterials on the barrier function of epithelial cells.
Shariq Ali (2014)
Microrheology and Heterogeneity in Biological Fluids: Approaches, Models and Applications
John Mellnik (2015)
Mucus as a Barrier for Biopharmaceuticals and Drug Delivery Systems
Hongbo Zhang (2014)
Enhanced pulmonary systemic delivery of protein drug via zwitterionic polymer conjugation.
Caroline Tsao (2020)
Enhanced Oral Delivery of Protein Drugs Using Zwitterion-Functionalized Nanoparticles to Overcome both the Diffusion and Absorption Barriers.
Wei Shan (2016)
Mucus as a barrier to drug delivery – understanding and mimicking the barrier properties.
M. Boegh (2015)
Drug Transport across Skin
Renata Vidor Contri (2016)
Hydrophobic-core PEGylated graft copolymer-stabilized nanoparticles composed of insoluble non-nucleoside reverse transcriptase inhibitors exhibit strong anti-HIV activity.
Anita M. Leporati (2016)
Enhancing the oral bioavailability of curcumin using solid lipid nanoparticles.
C. Ban (2019)
Targeted nanoparticles with novel non-peptidic ligands for oral delivery.
A. des Rieux (2013)
Nanophytomedicine: Concept to Clinic
Md. Abul Barkat (2020)
PEGylation of PLA nanoparticles to improve mucus-penetration and colloidal stability for oral delivery systems
Juliana Palacio (2016)
Enzyme-Functionalized PLGA Nanoparticles with Enhanced Mucus Permeation Rate
E. Samaridou (2014)
Emerging integrated nanohybrid drug delivery systems to facilitate the intravenous-to-oral switch in cancer chemotherapy.
Cong Luo (2014)
Poly(acrylic acid)-poly(ethylene glycol) nanoparticles designed for ophthalmic drug delivery.
Ana-Maria Vasi (2014)
Control of polymeric nanoparticle size to improve therapeutic delivery.
J. W. Hickey (2015)
Impact of Surface Polyethylene Glycol (PEG) Density on Biodegradable Nanoparticle Transport in Mucus ex Vivo and Distribution in Vivo.
Qingguo Xu (2015)
Pegylated Polyaspartamide-Polylactide-Based Nanoparticles Penetrating Cystic Fibrosis Artificial Mucus.
Emanuela Fabiola Craparo (2016)
Sub‐50 nm Nanoparticles with Biomimetic Surfaces to Sequentially Overcome the Mucosal Diffusion Barrier and the Epithelial Absorption Barrier
Xi Zhu (2016)
Nanoformulations for Vaginal Therapy
Željka Vanić (2017)
A slippery slope: On the origin, role and physiology of mucus☆
Farhan Taherali (2018)
Mucosal Delivery of Drugs and Biologics in Nanoparticles
Pavan Muttil (2020)
Mucin Thin Layers: A Model for Mucus-Covered Tissues
Valeria Rondelli (2019)
Influence of salt type and ionic strength on self-assembly of dextran sulfate-ciprofloxacin nanoplexes.
Marika Kutscher (2015)
Breaking the barricade of oral chemotherapy through polysaccharide nanocarrier.
Madhumita Dey (2019)
High transfection efficiency of quantum dot-antisense oligonucleotide nanoparticles in cancer cells through dual-receptor synergistic targeting.
Ming-Zhen Zhang (2014)
PLGA carriers for inhalation: where do we stand, where are we headed?
Ivana d'Angelo (2015)
Nanomedicine in the development of anti-HIV microbicides.
J. das Neves (2016)
Nanoscale metal particles as nanocarriers in targeted drug delivery system
Nurul Akmal Che Lah (2016)
Microstructural alterations of sputum in cystic fibrosis lung disease.
Gregg A. Duncan (2016)
The Mucus Barrier to Inhaled Gene Therapy.
Gregg A. Duncan (2016)See more