Mucoadhesive nanoparticles may disrupt the protective human mucus barrier by altering its microstructure.

Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
PLoS ONE (Impact Factor: 3.53). 06/2011; 6(6):e21547. DOI: 10.1371/journal.pone.0021547
Source: PubMed

ABSTRACT Mucus secretions typically protect exposed surfaces of the eyes and respiratory, gastrointestinal and female reproductive tracts from foreign entities, including pathogens and environmental ultrafine particles. We hypothesized that excess exposure to some foreign particles, however, may cause disruption of the mucus barrier. Many synthetic nanoparticles are likely to be mucoadhesive due to hydrophobic, electrostatic or hydrogen bonding interactions. We therefore sought to determine whether mucoadhesive particles (MAP) could alter the mucus microstructure, thereby allowing other foreign particles to more easily penetrate mucus. We engineered muco-inert probe particles 1 µm in diameter, whose diffusion in mucus is limited only by steric obstruction from the mucus mesh, and used them to measure possible MAP-induced changes to the microstructure of fresh human cervicovaginal mucus. We found that a 0.24% w/v concentration of 200 nm MAP in mucus induced a ∼10-fold increase in the average effective diffusivity of the probe particles, and a 2- to 3-fold increase in the fraction capable of penetrating physiologically thick mucus layers. The same concentration of muco-inert particles, and a low concentration (0.0006% w/v) of MAP, had no detectable effect on probe particle penetration rates. Using an obstruction-scaling model, we determined that the higher MAP dose increased the average mesh spacing ("pore" size) of mucus from 380 nm to 470 nm. The bulk viscoelasticity of mucus was unaffected by MAP exposure, suggesting MAP may not directly impair mucus clearance or its function as a lubricant, both of which depend critically on the bulk rheological properties of mucus. Our findings suggest mucoadhesive nanoparticles can substantially alter the microstructure of mucus, highlighting the potential of mucoadhesive environmental or engineered nanoparticles to disrupt mucus barriers and cause greater exposure to foreign particles, including pathogens and other potentially toxic nanomaterials.

Download full-text


Available from: Richard A Cone, Jul 09, 2014
1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The increasing interest in nanoparticles for advanced technologies, consumer products, and biomedical applications has led to great excitement about potential benefits but also concern over the potential for adverse human health effects. The gastrointestinal tract represents a likely route of entry for many nanomaterials, both directly through intentional ingestion or indirectly via nanoparticle dissolution from food containers or by secondary ingestion of inhaled particles. Additionally, increased utilisation of nanoparticles may lead to increased environmental contamination and unintentional ingestion via water, food animals, or fish. The gastrointestinal tract is a site of complex, symbiotic interactions between host cells and the resident microbiome. Accordingly, evaluation of nanoparticles must take into consideration not only absorption and extraintestinal organ accumulation but also the potential for altered gut microbes and the effects of this perturbation on the host. The existing literature was evaluated for evidence of toxicity based on these considerations. Focus was placed on three categories of nanomaterials: nanometals and metal oxides, carbon-based nanoparticles, and polymer/dendrimers with emphasis on those particles of greatest relevance to gastrointestinal exposures.
    01/2013; 3(1-2). DOI:10.1504/IJBNN.2013.054515
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mucus in the gastrointestinal tract remains a tenacious barrier that restricts the passage of many orally administered compounds into the GIT's epithelial layer and consequently into the systemic circulation. This results in significant decreases in the oral bioavailability of many therapeutic molecules. Nanoparticles offer an avenue to surpass this mucus barrier. They can be used as drug carriers to improve the bioavailability of many compounds that are restricted by mucus. Nanoparticles achieve penetration of the mucus barrier through a multitude of properties that they possess as their size, charge density, and surface functional groups which can all be tailored to achieve optimal penetration of the thick and fibrous mucus barrier. This article offers a quick review about the use of nanoparticles as drug carriers to increase mucus penetration in the gastro intestinal tract.
    01/2012; 2(4):173-4. DOI:10.5681/bi.2012.029
  • [Show abstract] [Hide abstract]
    ABSTRACT: The objective of this investigation was to fabricate ondansetron hydrochloride [OND] loaded mucoadhesive nanostructured lipid carriers [NLCs] for efficient delivery to brain through nasal route. Mucoadhesive NLCs thereby sustaining drug release for longer time in nasal cavity. NLCs were prepared by high pressure homogenization [HPH] technique using glycerol monostearate [GMS]; as solid lipid, Capryol 90; as liquid lipid, soya lecithin; as surfactant and poloxamer 188; as cosurfactant. In the fabrication of NLCs, Delonix regia gum [DRG], isolated from seeds of D. regia belonging to family fabiaceae was used as a mucoadhesive polymer. The NLCs were evaluated for particle size, morphology, drug-entrapment efficiency [%EE], mucoadhesive strength, in vitro drug release, histological examination, ex vivo permeation study, in vivo biodistribution and pharmacokinetic studies in the brain/blood following intravenous [i.v.] and intranasal [i.n.] administration. Particle size, PDI, Zeta potential was observed in the range of 92.28-135nm, 0.32-0.46, and -11.5 to -36.2 respectively. Prepared NLCs achieved thermodynamic stability, control release pattern with minor histopathological changes in sheep nasal mucosa. The significantly [P<0.05] higher values for selected batch was observed, when administered by i.n. route showed higher drug targeting efficiency [506%] and direct transport percentage [97.14%] which confirms the development of promising OND-loaded NLC for efficient nose-to-brain delivery.
    Colloids and surfaces B: Biointerfaces 07/2014; 122C:143-150. DOI:10.1016/j.colsurfb.2014.06.037 · 4.29 Impact Factor