Nanoparticle penetration of human cervicovaginal mucus: The effect of polyvinyl alcohol
Therapeutic nanoparticles must rapidly penetrate the mucus secretions lining the surfaces of the respiratory, gastrointestinal and cervicovaginal tracts to efficiently reach the underlying tissues. Whereas most polymeric nanoparticles are highly mucoadhesive, we previously discovered that a dense la...
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| Published in | Journal of controlled release Vol. 192; pp. 202 - 208 |
|---|---|
| Main Authors | , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier B.V
28.10.2014
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Therapeutic nanoparticles must rapidly penetrate the mucus secretions lining the surfaces of the respiratory, gastrointestinal and cervicovaginal tracts to efficiently reach the underlying tissues. Whereas most polymeric nanoparticles are highly mucoadhesive, we previously discovered that a dense layer of low MW polyethylene glycol (PEG) conferred a sufficiently hydrophilic and uncharged surface to effectively minimize mucin-nanoparticle adhesive interactions, allowing well-coated particles to rapidly diffuse through human mucus. Here, we sought to investigate the influence of surface coating by polyvinyl alcohol (PVA), a relatively hydrophilic and uncharged polymer routinely used as a surfactant to formulate drug carriers, on the transport of nanoparticles in fresh human cervicovaginal mucus. We found that PVA-coated polystyrene (PS) particles were immobilized, with speeds at least 4000-fold lower in mucus than in water, regardless of the PVA molecular weight or incubation concentration tested. Nanoparticles composed of poly(lactide-co-glycolide) (PLGA) or diblock copolymers of PEG-PLGA were similarly immobilized when coated with PVA (slowed 29,000- and 2500-fold, respectively). PVA coatings could not be adequately removed upon washing, and the residual PVA prevented sufficient coating with Pluronic F127 capable of reducing particle mucoadhesion. In contrast to PVA-coated particles, the similar sized PEG-coated formulations were slowed only ~6- to 10-fold in mucus compared to in water. Our results suggest that incorporating PVA in the particle formulation process may lead to the formation of mucoadhesive particles for many nanoparticulate systems. Thus, alternative methods for particle formulation, based on novel surfactants or changes in the formulation process, should be identified and developed in order to produce mucus-penetrating particles for mucosal applications.
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| AbstractList | Therapeutic nanoparticles must rapidly penetrate the mucus secretions lining the surfaces of the respiratory, gastrointestinal and cervicovaginal tracts to efficiently reach the underlying tissues. Whereas most polymeric nanoparticles are highly mucoadhesive, we previously discovered that a dense layer of low MW polyethylene glycol (PEG) conferred a sufficiently hydrophilic and uncharged surface to effectively minimize mucin-nanoparticle adhesive interactions, allowing well-coated particles to rapidly diffuse through human mucus. Here, we sought to investigate the influence of surface coating by polyvinyl alcohol (PVA), a relatively hydrophilic and uncharged polymer routinely used as a surfactant to formulate drug carriers, on the transport of nanoparticles in fresh human cervicovaginal mucus. We found that PVA-coated polystyrene (PS) particles were immobilized, with speeds at least 4,000-fold lower in mucus than in water, regardless of the PVA molecular weight or incubation concentration tested. Nanoparticles composed of poly(lactide-co-glycolide) (PLGA) or diblock copolymers of PEG-PLGA were similarly immobilized when coated with PVA (slowed 29,000- and 2,500-fold, respectively). PVA coatings could not be adequately removed upon washing, and the residual PVA prevented sufficient coating with Pluronic F127 capable of reducing particle mucoadhesion. In contrast to PVA-coated particles, the similar sized PEG-coated formulations were slowed only ~6- to 10-fold in mucus compared to in water. Our results suggest incorporating PVA in the particle formulation process may lead to the formation of mucoadhesive particles for many nanoparticulate systems. Thus, alternative methods for particle formulation, based on novel surfactants or changes in the formulation process, should be identified and developed in order to produce mucus-penetrating particles for mucosal applications. Therapeutic nanoparticles must rapidly penetrate the mucus secretions lining the surfaces of the respiratory, gastrointestinal and cervicovaginal tracts to efficiently reach the underlying tissues. Whereas most polymeric nanoparticles are highly mucoadhesive, we previously discovered that a dense layer of low MW polyethylene glycol (PEG) conferred a sufficiently hydrophilic and uncharged surface to effectively minimize mucin-nanoparticle adhesive interactions, allowing well-coated particles to rapidly diffuse through human mucus. Here, we sought to investigate the influence of surface coating by polyvinyl alcohol (PVA), a relatively hydrophilic and uncharged polymer routinely used as a surfactant to formulate drug carriers, on the transport of nanoparticles in fresh human cervicovaginal mucus. We found that PVA-coated polystyrene (PS) particles were immobilized, with speeds at least 4000-fold lower in mucus than in water, regardless of the PVA molecular weight or incubation concentration tested. Nanoparticles composed of poly(lactide-co-glycolide) (PLGA) or diblock copolymers of PEG-PLGA were similarly immobilized when coated with PVA (slowed 29,000- and 2500-fold, respectively). PVA coatings could not be adequately removed upon washing, and the residual PVA prevented sufficient coating with Pluronic F127 capable of reducing particle mucoadhesion. In contrast to PVA-coated particles, the similar sized PEG-coated formulations were slowed only ~6- to 10-fold in mucus compared to in water. Our results suggest that incorporating PVA in the particle formulation process may lead to the formation of mucoadhesive particles for many nanoparticulate systems. Thus, alternative methods for particle formulation, based on novel surfactants or changes in the formulation process, should be identified and developed in order to produce mucus-penetrating particles for mucosal applications. [Display omitted] Therapeutic nanoparticles must rapidly penetrate the mucus secretions lining the surfaces of the respiratory, gastrointestinal and cervicovaginal tracts to efficiently reach the underlying tissues. Whereas most polymeric nanoparticles are highly mucoadhesive, we previously discovered that a dense layer of low MW polyethylene glycol (PEG) conferred a sufficiently hydrophilic and uncharged surface to effectively minimize mucin-nanoparticle adhesive interactions, allowing well-coated particles to rapidly diffuse through human mucus. Here, we sought to investigate the influence of surface coating by polyvinyl alcohol (PVA), a relatively hydrophilic and uncharged polymer routinely used as a surfactant to formulate drug carriers, on the transport of nanoparticles in fresh human cervicovaginal mucus. We found that PVA-coated polystyrene (PS) particles were immobilized, with speeds at least 4000-fold lower in mucus than in water, regardless of the PVA molecular weight or incubation concentration tested. Nanoparticles composed of poly(lactide-co-glycolide) (PLGA) or diblock copolymers of PEG-PLGA were similarly immobilized when coated with PVA (slowed 29,000- and 2500-fold, respectively). PVA coatings could not be adequately removed upon washing, and the residual PVA prevented sufficient coating with Pluronic F127 capable of reducing particle mucoadhesion. In contrast to PVA-coated particles, the similar sized PEG-coated formulations were slowed only ~6- to 10-fold in mucus compared to in water. Our results suggest that incorporating PVA in the particle formulation process may lead to the formation of mucoadhesive particles for many nanoparticulate systems. Thus, alternative methods for particle formulation, based on novel surfactants or changes in the formulation process, should be identified and developed in order to produce mucus-penetrating particles for mucosal applications. |
| Author | Zhong, Weixi Fu, Jie Lai, Samuel K. Happe, Christina Hanes, Justin Hung, Amy Zhang, Michael Yang, Ming Fridley, Colleen Wang, Ying-Ying Anonuevo, Abraham Yu, Tao |
| AuthorAffiliation | 2 Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205 (USA) 6 Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21287 (USA) 5 Center for Cancer Nanotechnology Excellence, Institute for NanoBioTechnology, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218 (USA) 1 Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21287 4 Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore, MD 21287 (USA) 3 Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218 (USA) |
| AuthorAffiliation_xml | – name: 2 Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205 (USA) – name: 3 Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218 (USA) – name: 4 Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore, MD 21287 (USA) – name: 6 Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21287 (USA) – name: 1 Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21287 – name: 5 Center for Cancer Nanotechnology Excellence, Institute for NanoBioTechnology, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218 (USA) |
| Author_xml | – sequence: 1 givenname: Ming surname: Yang fullname: Yang, Ming organization: Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21287, USA – sequence: 2 givenname: Samuel K. surname: Lai fullname: Lai, Samuel K. organization: Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21287, USA – sequence: 3 givenname: Tao surname: Yu fullname: Yu, Tao organization: Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21287, USA – sequence: 4 givenname: Ying-Ying surname: Wang fullname: Wang, Ying-Ying organization: Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21287, USA – sequence: 5 givenname: Christina surname: Happe fullname: Happe, Christina organization: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218, USA – sequence: 6 givenname: Weixi surname: Zhong fullname: Zhong, Weixi organization: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA – sequence: 7 givenname: Michael surname: Zhang fullname: Zhang, Michael organization: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218, USA – sequence: 8 givenname: Abraham surname: Anonuevo fullname: Anonuevo, Abraham organization: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218, USA – sequence: 9 givenname: Colleen surname: Fridley fullname: Fridley, Colleen organization: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218, USA – sequence: 10 givenname: Amy surname: Hung fullname: Hung, Amy organization: Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21287, USA – sequence: 11 givenname: Jie surname: Fu fullname: Fu, Jie organization: Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21287, USA – sequence: 12 givenname: Justin surname: Hanes fullname: Hanes, Justin email: hanes@jhu.edu organization: Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21287, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25090196$$D View this record in MEDLINE/PubMed |
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| Copyright | 2014 Elsevier B.V. Copyright © 2014 Elsevier B.V. All rights reserved. 2014 Elsevier B.V. All rights reserved. 2014 |
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| Keywords | Drug delivery Mucoadhesion Mucus-penetrating particles Surfactant Biodegradable polymers |
| Language | English |
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| Notes | These authors contributed equally to this work. Current address: Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Campus box 7362, Chapel Hill, NC 27599 |
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| SubjectTerms | Adhesiveness Biodegradable polymers Cervix Mucus - metabolism Coated Materials, Biocompatible - chemistry Coated Materials, Biocompatible - metabolism Drug Carriers - chemistry Drug Carriers - metabolism Drug delivery Humans Mucoadhesion Mucus-penetrating particles Nanoparticles - chemistry Nanoparticles - metabolism Polyesters - chemistry Polyesters - metabolism Polyethylene Glycols - chemistry Polyethylene Glycols - metabolism Polyglactin 910 - chemistry Polyglactin 910 - metabolism Polyvinyl Alcohol - chemistry Polyvinyl Alcohol - metabolism Surfactant |
| Title | Nanoparticle penetration of human cervicovaginal mucus: The effect of polyvinyl alcohol |
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