Pegylated nanoparticles based on poly(methyl vinyl ether-co-maleic anhydride): preparation and evaluation of their bioadhesive properties

Yoncheva, Krassimira; Lizarraga, Elena; Irache, Juan M.

doi:10.1016/j.ejps.2004.12.002

Cited by 136 publications

(91 citation statements)

References 32 publications

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“…PEG coatings have been widely used in the development of polymeric drug carriers, including particles composed of biodegradable polyesters (27,28) and polyanhydrides (29)(30)(31)(32). PEG coatings reduce aggregation and enhance the blood circulation times of biodegradable nanoparticles designed for drug delivery by reducing particle detection by the reticuloendothelial system (i.e., ''stealth nanoparticles'') (33-35).…”

Section: Discussionmentioning

confidence: 99%

Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier

Tang¹,

Dawson²,

Lai

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

399

286

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Protective mucus coatings typically trap and rapidly remove foreign particles from the eyes, gastrointestinal tract, airways, nasopharynx, and female reproductive tract, thereby strongly limiting opportunities for controlled drug delivery at mucosal surfaces. No synthetic drug delivery system composed of biodegradable polymers has been shown to penetrate highly viscoelastic human mucus, such as non-ovulatory cervicovaginal mucus, at a significant rate. We prepared nanoparticles composed of a biodegradable diblock copolymer of poly(sebacic acid) and poly(ethylene glycol) (PSA-PEG), both of which are routinely used in humans. In fresh undiluted human cervicovaginal mucus (CVM), which has a bulk viscosity approximately 1,800-fold higher than water at low shear, PSA-PEG nanoparticles diffused at an average speed only 12-fold lower than the same particles in pure water. In contrast, similarly sized biodegradable nanoparticles composed of PSA or poly(lacticco-glycolic acid) (PLGA) diffused at least 3,300-fold slower in CVM than in water. PSA-PEG particles also rapidly penetrated sputum expectorated from the lungs of patients with cystic fibrosis, a disease characterized by hyperviscoelastic mucus secretions. Rapid nanoparticle transport in mucus is made possible by the efficient partitioning of PEG to the particle surface during formulation. Biodegradable polymeric nanoparticles capable of overcoming human mucus barriers and providing sustained drug release open significant opportunities for improved drug and gene delivery at mucosal surfaces.cystic fibrosis ͉ drug delivery ͉ gene therapy ͉ mucosa ͉ mucus-penetrating particle

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Section: Discussionmentioning

confidence: 99%

Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier

Tang¹,

Dawson²,

Lai

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

399

286

View full text Add to dashboard Cite

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“…The shaded region represents the confirmed range of PEG MW and particle ζ-potential (i.e., PEG surface coverage), and the hatched region an additional predicted range that provides a mucoinert coating. A) Present study; B) PEG-coated PS nanoparticles; [5] C) PEGylated poly(methyl vinyl ether-co-maleic anhydride) nanoparticles; [16,17] D) poly(lactic acid)-PEG nanoparticles [15] (*: mucoadhesion was not observed based on adhesion to an in vitro mucin-secreting cell line); E) PEG-coated poly(ethyl-2-cyanoacrylate) nanospheres (mucoadhesion was inferred from improved bioavailability compared to free drug). [18] Characterization of COOH-and PEG-modified PS nanoparticles and ratios of their ensemble average diffusion coefficients in mucus PEG coverage percentage was based on the number of COOH groups available for conjugation on the surface of PS-COOH nanoparticles (see Experimental Section).…”

Section: Methodsmentioning

confidence: 99%

Addressing the PEG Mucoadhesivity Paradox to Engineer Nanoparticles that “Slip” through the Human Mucus Barrier

et al. 2008

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Outsmarting the barrier: Conventional poly(ethylene glycol) (PEG) coated particles (green with light purple border) are immobilized in human mucus networks by adhesive interactions (red) with the mucus mesh (black lines). A dense, low molecular weight PEG coating (blue) uniquely endows nanoparticles with a mucoinert surface that enables their rapid mucus penetration (trajectory indicated by grey line).

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“…Regarding ocular drug delivery systems, smaller particles are characterized by greater surface area available for conjugation between the cornea and proniosomal gel formula (Yoncheva et al, 2005).…”

Section: Vesicle Size Analysismentioning

confidence: 99%

Ocular ketoconazole-loaded proniosomal gels: formulation, ex vivo corneal permeation and in vivo studies

2017

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Context: Vesicular drug carriers for ocular delivery have gained a real potential. Proniosomal gels as ocular drug carriers have been proven to be an effective way to improve bioavailability and patient compliance. Objective: Formulation and in vitro/ex vivo/in vivo characterization of ketoconazole (KET)-loaded proniosomal gels for the treatment of ocular keratitis. Materials and methods: The effect of formulation variables; HLB value, type and concentration of non-ionic surfactants (Tweens, Spans, Brijs and Pluronics) with or without lecithin on the entrapment efficiency (EE%), vesicle size and in vitro KET release was evaluated. An ex vivo corneal permeation study to determine the level of KET in the external eye tissue of albino rabbits and an in vivo assessment of the level of KET in the aqueous humors were performed. Results and discussion: In vivo evaluation showed an increase in bioavailability up to 20-folds from the optimum KET proniosomal gel formula in the aqueous humor compared to drug suspension (KET-SP). The selected formulae were composed of spans being hydrophobic suggesting the potential use of a more hydrophobic surfactant as Span during the formulation of formulae. Factors that stabilize the vesicle membrane and increase the entrapment efficiency of KET (namely low HLB, long alkyl chain, high phase transition temperature) slowed down the release profile. Conclusions: Proniosomal gels as drug delivery carriers were proven to be a promising approach to increase corneal contact and permeation as well as retention time in the eye resulting in a sustained action and enhanced bioavailability.

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Pegylated nanoparticles based on poly(methyl vinyl ether-co-maleic anhydride): preparation and evaluation of their bioadhesive properties

Cited by 136 publications

References 32 publications

Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier

Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier

Addressing the PEG Mucoadhesivity Paradox to Engineer Nanoparticles that “Slip” through the Human Mucus Barrier

Ocular ketoconazole-loaded proniosomal gels: formulation, ex vivo corneal permeation and in vivo studies

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