Dataset Information

Comparative study of mucoadhesive and mucus-penetrative nanoparticles based on phospholipid complex to overcome the mucus barrier for inhaled delivery of baicalein.

ABSTRACT: Efficient mucosal delivery remains a major challenge for the reason of the respiratory tract mucus act as a formidable barrier to nanocarriers by trapping and clearing foreign particulates. The surface property of nanoparticles determines their retention and penetration ability within the respiratory tract mucus. However, the interaction between nanoparticles and mucus, and how these interactions impact distribution has not been extensively investigated. In this study, polymeric nanoparticles loaded with a baicalein-phospholipid complex were modified with two kinds of polymers, mucoadhesive and mucus-penetrative polymer. Systematic investigations on the physicochemical property, mucus penetration, transepithelial transport, and tissue distribution were performed to evaluate the interaction of nanoparticles with the respiratory tract. Both nanoparticles had a similar particle size and good biocompatibility, exhibited a sustained-release profile, but showed a considerable difference in zeta potential. Interestingly, mucus-penetrative nanoparticles exhibited a higher diffusion rate in mucus, deeper penetration across the mucus layer, enhanced in vitro cellular uptake, increased drug distribution in airways, and superior local distribution and bioavailability as compared to mucoadhesive nanoparticles. These results indicate the potential of mucus-penetrative nanoparticles in design of a rational delivery system to improve the efficiency of inhaled therapy by promoting mucus penetration and increasing local distribution and bioavailability.

SUBMITTER: Dong W

PROVIDER: S-EPMC7488487 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Comparative study of mucoadhesive and mucus-penetrative nanoparticles based on phospholipid complex to overcome the mucus barrier for inhaled delivery of baicalein.

Dong Wujun W Ye Jun J Zhou Junzhuo J Wang Weijue W Wang Hongliang H Zheng Xu X Yang Yanfang Y Xia Xuejun X Liu Yuling Y

Acta pharmaceutica Sinica. B 20191018 8

Efficient mucosal delivery remains a major challenge for the reason of the respiratory tract mucus act as a formidable barrier to nanocarriers by trapping and clearing foreign particulates. The surface property of nanoparticles determines their retention and penetration ability within the respiratory tract mucus. However, the interaction between nanoparticles and mucus, and how these interactions impact distribution has not been extensively investigated. In this study, polymeric nanoparticles lo ...[more]

PMID: 32963951

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Project description: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.

Project description:Pharmaceutical approaches based on nanotechnologies and the development of eye drops composed of the mucoadhesive polymers chitosan and hyaluronic acid are emerging strategies for the efficient treatment of ocular diseases. These innovative nanoparticulate systems aim to increase drugs' bioavailability at the ocular surface. For the successful development of these systems, the evaluation of mucoahesiveness (the interaction between the ocular delivery system and mucins present on the eye) is of utmost importance. In this context, the aim of the present work was to investigate the mucoadhesivity of a novel nanoparticle eye drop formulation containing an antibiotic (ceftazidime) intended to treat eye infections. Eye drop formulations comprised a polymer (hydroxypropyl) methyl cellulose (HPMC) 0.75% (w/v) in an isotonic solution incorporating chitosan/sodium tripolyphosphate (TPP)-hyaluronic acid-based nanoparticles containing ceftazidime. The viscosity of the nanoparticles, and the gels incorporating the nanoparticles were characterized in contact with mucin at different mass ratios, allowing the calculation of the rheological synergism parameter (??). Results showed that at different nanoparticle eye formulation:mucin weight ratios, a minimum in viscosity occurred which resulted in a negative rheological synergism. Additionally, the results highlighted the mucoadhesivity of the novel ocular formulation and its ability to interact with the ocular surface, thus increasing the drug residence time in the eye. Moreover, the in vitro release and permeation studies showed a prolonged drug release profile from the chitosan/TPP-hyaluronic acid nanoparticles gel formulation. Furthermore, the gel formulations were not cytotoxic on ARPE-19 and HEK293T cell lines, evaluated by the metabolic and membrane integrity tests. The formulation was stable and the drug active, as shown by microbiological studies. In conclusion, chitosan/TPP-hyaluronic acid nanoparticle eye drop formulations are a promising platform for ocular drug delivery with enhanced mucoadhesive properties.

Dataset Information

Comparative study of mucoadhesive and mucus-penetrative nanoparticles based on phospholipid complex to overcome the mucus barrier for inhaled delivery of baicalein.

Publications

Comparative study of mucoadhesive and mucus-penetrative nanoparticles based on phospholipid complex to overcome the mucus barrier for inhaled delivery of baicalein.

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