Stealth® PEGylated polycyanoacrylate nanoparticles for intravenous administration and splenic targeting

Peracchia, Maria Teresa; Fattal, Elias; Desmaële, Didier; Besnard, Madeleine; Noël, Jean‐Pierre; Gomis, J.M; Appel, M.; d’Angelo, Jean; Couvreur, Patrick

doi:10.1016/s0168-3659(99)00063-2

Cited by 359 publications

(204 citation statements)

References 18 publications

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“…[21][22][23] Only pegylated polyalkylcyanoacrylate nanoparticles have lower MPS uptake and prolonged blood circulation in vivo. 24 Brain delivery with PBCA nanoparticles Adsorbed onto polysorbate 80-coated PBCA nanoparticles administered intravenously compounds with poor brain diffusion as diverse as doxorubicin, 25,26 loperamide, 27 tubocurarine, 28 the hexapeptide dalargin 6,7 were successfully delivered to the brain, where they induced a pharmacological effect (for review, see Kreuter 29 ). The chemical nature of the overcoating surfactant is of importance, because only polysorbates, not poloxamers (184, 188, 388, or 407), poloxamine 908, Cremophors (EZ or RH40) or polyoxyethylene(23)-laurylether, led to a CNS pharmacological effect of dalargin.…”

Section: General Considerationsmentioning

confidence: 99%

Drug transport to brain with targeted nanoparticles

2005

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Summary: Nanoparticle drug carriers consist of solid biodegradable particles in size ranging from 10 to 1000 nm (50 -300 nm generally). They cannot freely diffuse through the bloodbrain barrier (BBB) and require receptor-mediated transport through brain capillary endothelium to deliver their content into the brain parenchyma. Polysorbate 80-coated polybutylcyanoacrylate nanoparticles can deliver drugs to the brain by a still debated mechanism. Despite interesting results these nanoparticles have limitations, discussed in this review, that may preclude, or at least limit, their potential clinical applications. Long-circulating nanoparticles made of methoxypoly(ethylene glycol)-polylactide or poly(lactide-co-glycolide) (mPEG-PLA/ PLGA) have a good safety profiles and provide drug-sustained release. The availability of functionalized PEG-PLA permits to prepare target-specific nanoparticles by conjugation of cell surface ligand. Using peptidomimetic antibodies to BBB transcytosis receptor, brain-targeted pegylated immunonanoparticles can now be synthesized that should make possible the delivery of entrapped actives into the brain parenchyma without inducing BBB permeability alteration. This review presents their general properties (structure, loading capacity, pharmacokinetics) and currently available methods for immunonanoparticle preparation.

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Section: General Considerationsmentioning

confidence: 99%

Drug transport to brain with targeted nanoparticles

2005

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“…12 Recently long circulating nanoparticles were obtained by surface modification with dysopsonic polymers such as poly(ethylene glycol). 13 Polycyanoacrylate nanoparticles were recently used for drug targeting to brain 14 , spleen 15 and intestinal epithelium. 16 Majority of the above targeting approaches utilized surface modification mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and Biodistribution Studies of Doxorubicin Loaded Poly(butyl Cyanoacrylate) Nanoparticles Synthesized by Two Different Techniques

Reddy¹,

Murthy²

2004

BIOMED PAP

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The aim of the study is to determine and compare the pharmacokinetics and tissue distribution of Doxorubicin (Dox) delivered as solution or through nanoparticles after intravenous (i.v.) and intraperitoneal (i.p.) injection. Doxorubicin loaded poly(butyl cyanoacrylate) nanoparticles were synthesized by dispersion polymerization (DP) and emulsion polymerization (EP) techniques. The drug loaded DP and EP nanoparticles were administered by i.v. or i.p. routes and the respective pharmacokinetics and tissue distribution were determined. Both types of nanoparticles significantly enhanced the elimination half-life (T 1/2 ), mean residence time (MRT) AUC [0][1][2][3][4][5][6][7][8] , AUC 0-∞ and AUMC 0-8 of Dox in blood after i.v. injection. Dox delivered through DP nanoparticles rapidly disappeared from blood and distributed to the organs of reticuloendothelial system (RES). But, the clearance of Dox delivered through EP nanoparticles from blood was slower than this of the DP nanoparticles and Dox solution. After i.p. injection, the Dox loaded into DP nanoparticles quickly appeared in blood and undergone rapid distribution to the organs of RES, while the Dox loaded into EP nanoparticles absorbed slowly into blood and remained in the circulation for longer time. The absorption into blood of Dox delivered through DP and EP nanoparticles after i.p. injection was relatively rapid and higher than Dox solution. The T 1/2 , MRT, AUC [0][1][2][3][4][5][6][7][8] , AUC 0-∞ and AUMC 0-8 of Dox in blood were significantly higher and the clearance (Cl) was lower than for the Dox solution after i.p. injection. The tissue concentrations of Dox delivered through nanoparticles after i.p. injection were significantly lower than after i.v. injection. The bioavailability (F) of Dox was greatly enhanced by DP (∼1.9 fold) and EP nanoparticles (∼2.12 fold) compared to Dox solution after i.p. injection. EP nanoparticles significantly enhanced the bioavailability, MRT, T 1/2 , AUC 0-8 , AUC 0-∞ and AUMC 0-8 of Dox than DP nanoparticles. This signifies the advantage of EP nanoparticles in increasing the elimination half-life of Dox both after i.v. and i.p. injection and enhanced bioavailability after i.p. injection, which is expected to improve the therapeutic efficacy of Dox and reduce the Dox-associated systemic toxicity. Importantly, both DP and EP nanoparticles greatly reduced the distribution of Dox to heart both after i.v. and i.p. injection, suggesting their potential in reducing Dox-associated cardiotoxicity.

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“…(22,23,41) To further increase the attractiveness of neutral, small particles for drug transmission via the lung, PEGylated particles have been shown to increase time in the bloodstream and decrease hepatic toxicity when compared to non-PEGylated particles. (42) Our study shows that neutral particles do not increase CBF at the axoneme level; therefore, not only do PEGylated particles escape entrapment by mucins, but they also effect no changes in clearance by stimulating cilia beating. Conversely, large particles (500 nm COOH-modified) speed up CBF by direct mechanical interaction with the axoneme.…”

Section: Discussionmentioning

confidence: 54%

Particulate Matter in Cigarette Smoke Increases Ciliary Axoneme Beating Through Mechanical Stimulation

Navarrette¹,

Sisson²,

Nance

et al. 2012

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Background: The lung's ability to trap and clear foreign particles via the mucociliary elevator is an important mechanism for protecting the lung against respirable irritants and microorganisms. Although cigarette smoke (CS) exposure and particulate inhalation are known to alter mucociliary clearance, little is known about how CS and nanoparticles (NPs) modify cilia beating at the cytoskeletal infrastructure, or axonemal, level. Methods: We used a cell-free model to introduce cigarette smoke extract (CSE) and NPs with variant size and surface chemistry to isolated axonemes and measured changes in ciliary motility. We hypothesized that CSE would alter cilia beating and that alterations in ciliary beat frequency (CBF) due to particulate matter would be size-and surface chemistry-dependent. Demembranated axonemes were isolated from ciliated bovine tracheas and exposed to adenosine triphosphate (ATP) to initiate motility. CBF was measured in response to 5% CSE, CSE filtrate, and carboxyl-modified (COOH), sulphate (SO 4 )-modified (sulfonated), or PEG-coated polystyrene (PS) latex NPs ranging in size from 40 nm to 500 nm. Results: CSE concentrations as low as 5% resulted in rapid, significant stimulation of CBF ( p < 0.05 vs. baseline control). Filtering CSE through a 0.2-lm filter attenuated this effect. Introduction of sulphate-modified PS beads *300 nm in diameter resulted in a similar increase in CBF above baseline ATP levels. Uncharged, PEG-coated beads had no effect on CBF regardless of size. Similarly, COOH-coated particles less than 200 nm in diameter did not alter ciliary motility. However, COOH-coated PS particles larger than 300 nm increased CBF significantly and increased the number of motile points. Conclusions: These data show that NPs, including those found in CSE, mechanically stimulate axonemes in a size-and surface chemistry-dependent manner. Alterations in ciliary motility due to physicochemical properties of NPs may be important for inhalational lung injury and efficient drug delivery of respirable particles.

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Stealth® PEGylated polycyanoacrylate nanoparticles for intravenous administration and splenic targeting

Cited by 359 publications

References 18 publications

Drug transport to brain with targeted nanoparticles

Drug transport to brain with targeted nanoparticles

Pharmacokinetics and Biodistribution Studies of Doxorubicin Loaded Poly(butyl Cyanoacrylate) Nanoparticles Synthesized by Two Different Techniques

Particulate Matter in Cigarette Smoke Increases Ciliary Axoneme Beating Through Mechanical Stimulation

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