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Yoo, Hyuk Sang; Oh, Jong Eun; Lee, Keun Hyeung; Park, Tae Gwan

doi:10.1023/a:1018908421434

Cited by 195 publications

(66 citation statements)

References 10 publications

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“…The high surface-areato-volume ratio of small nanoparticles typically leads to fast diffusion of drugs out of particles (i.e., the burst effect) within hours upon in vitro or in vivo application (41,42). As the size of drug-loaded particles increases, drug-release kinetics are usually greatly improved, and sustained release of therapeutics over days and even months can be achieved with enhanced therapeutic efficacies (30,43,44).…”

Section: Discussionmentioning

confidence: 99%

Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus

Lai¹,

O’Hanlon

Harrold

et al. 2007

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

895

1,012

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Nanoparticles larger than the reported mesh-pore size range (10 -200 nm) in mucus have been thought to be much too large to undergo rapid diffusional transport through mucus barriers. However, large nanoparticles are preferred for higher drug encapsulation efficiency and the ability to provide sustained delivery of a wider array of drugs. We used high-speed multiple-particle tracking to quantify transport rates of individual polymeric particles of various sizes and surface chemistries in samples of fresh human cervicovaginal mucus. Both the mucin concentration and viscoelastic properties of these cervicovaginal samples are similar to those in many other human mucus secretions. Unexpectedly, we found that large nanoparticles, 500 and 200 nm in diameter, if coated with polyethylene glycol, diffused through mucus with an effective diffusion coefficient (D eff) only 4-and 6-fold lower than that for the same particles in water (at time scale ‫؍‬ 1 s). In contrast, for smaller but otherwise identical 100-nm coated particles, D eff was 200-fold lower in mucus than in water. For uncoated particles 100 -500 nm in diameter, D eff was 2,400-to 40,000-fold lower in mucus than in water. Much larger fractions of the 100-nm particles were immobilized or otherwise hindered by mucus than the large 200-to 500-nm particles. Thus, in contrast to the prevailing belief, these results demonstrate that large nanoparticles, if properly coated, can rapidly penetrate physiological human mucus, and they offer the prospect that large nanoparticles can be used for mucosal drug delivery. drug delivery ͉ mucosal tissues ͉ particle tracking ͉ PEG

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Section: Discussionmentioning

confidence: 99%

Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus

Lai¹,

O’Hanlon

Harrold

et al. 2007

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

895

1,012

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“…As microscopias eletrônicas de varredura [56][57][58][59][60] (MEV) ou de transmissão 59,61,62 (MET) têm sido muito empregadas na obtenção de informações relativas à forma e ao tamanho das nanopartículas. A MET pode permitir também a diferenciação entre nanocápsulas e nanoesferas, possibilitando, inclusive, a determinação da espessura da parede das nanocápsulas 63,64 .…”

Section: Avaliação Morfológicaunclassified

Caracterização e estabilidade físico-química de sistemas poliméricos nanoparticulados para administração de fármacos

et al. 2003

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Recebido em 28/10/02; aceito em 27/2/03 PHYSICOCHEMICAL CHARACTERIZATION AND STABILITY OF THE POLYMERIC NANOPARTICLE SYSTEMS FOR DRUG ADMINISTRATION. Polymeric nanoparticle systems such as nanocapsules and nanospheres present potential applications for the administration of therapeutic molecules. The physico-chemical characteristics of nanoparticle suspensions are important pre-requisites of the success of any dosage form development. The purpose of this review is to present the state of the art regarding the physico-chemical characterization of these drug carriers, in terms of the particle size distribution, the morphology, the polymer molecular weight, the surface charge, the drug content and the in vitro drug release profiles. Part of the review is devoted to the description of the techniques to improve the stability of colloidal systems.Keywords: nanoparticles; polymers; characterization. INTRODUÇÃOO controle da liberação de fármacos em sítios de ação específi-cos, através da utilização de vetores, capazes de permitir a otimização da velocidade de cedência e do regime de dosagem das substâncias, tem sido uma área de intensa pesquisa nos últimos dez anos. Dentre os vetores, incluem-se as micropartículas e os sistemas coloidais (lipossomas e nanopartículas). As nanopartículas, constituídas por polímeros biodegradáveis, têm atraído maior atenção dos pesquisadores em relação aos lipossomas, devido às suas potencialidades terapêuticas, à maior estabilidade nos fluídos biológicos e durante o armazenamento 1-3 . As nanopartículas poliméricas são sistemas carreadores de fármacos que apresentam diâmetro inferior a 1 µm. O termo nanopartícula inclui as nanocápsulas e as nanoesferas, as quais diferem entre si segundo a composição e organização estrutural (Figura 1). As nanocápsulas são constituídas por um invólucro polimérico disposto ao redor de um núcleo oleoso, podendo o fármaco estar dissolvido neste núcleo e/ou adsorvido à parede polimérica. Por outro lado, as nanoesferas, que não apresentam óleo em sua composição, são formadas por uma matriz polimérica, onde o fármaco pode ficar retido ou adsorvido 2,4,5 . Estes sistemas têm sido desenvolvidos visando inúmeras aplicações terapêuticas, sendo planejados, principalmente, para administração parenteral, oral ou oftálmica. Uma das áreas mais promissoras na utilização das nanopartículas é a vetorização de fármacos anticancerígenos 2,6-8 e de antibióticos 2,9,10 , principalmente através de administração parenteral, almejando uma distribuição mais seletiva dos mesmos e, assim, um aumento do índice terapêutico. Com relação à administração oral de nanopartículas, as pesquisas têm sido direcionadas especialmente à: a) diminuição dos efeitos colaterais de certos fármacos, destacando-se os antiinflamatórios não-esteróides (diclofenaco 11,12 , indometacina 13-15 ), os quais causam freqüentemente irritação à mucosa gastrintestinal e b) proteção de fármacos degradáveis no trato gastrintestinal, como peptídeos 16,17 , proteínas 8,18 e/ou hormônios 19 , aumentando a biodisponi...

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“…In comparison, 82 % of Ptxl was released within 24 h from Ptxl-PLA NE (Figure 2 b). The release of Ptxl from Ptxl-LA 50 NC was slower than that from Ptxl-LA 25 NC, presumably because of the higher molecular weight of Ptxl-LA 50 and more compact aggregation in the particle. The in vitro toxicities of NCs are correlated to the amount of Ptxl released; they show strong correlation with drug loadings (Figure 2 c).…”

mentioning

confidence: 92%

“…The in vitro toxicities of NCs are correlated to the amount of Ptxl released; they show strong correlation with drug loadings (Figure 2 c). The IC 50 values of Ptxl-LA 15 , Ptxl-LA 25 and Ptxl-LA 50 NCs with similar sizes ( % 100 nm), which were determined by MTT (MTT = 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays in PC-3 cells, are 111, 370, and 855 nm, respectively. The IC 50 value of Ptxl-LA 15 NC is nearly identical to that of free Ptxl (87 nm), while the IC 50 value of the Ptxl-LA 50 NC is an order of magnitude higher.…”

mentioning

confidence: 94%

Paclitaxel‐Initiated, Controlled Polymerization of Lactide for the Formulation of Polymeric Nanoparticulate Delivery Vehicles

2008

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Paclitaxel–polylactide nanoconjugates were prepared by the site‐specific polymerization of lactide mediated by a paclitaxel–metal complex followed by nanoprecipitation (see scheme). The resulting nanoconjugates have nearly 100 % paclitaxel incorporation efficiencies and predefined drug loadings, and are less than 100 nm in diameter. The drug burst release effect is completely eliminated with this drug delivery vehicle.

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Cited by 195 publications

References 10 publications

Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus

Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus

Caracterização e estabilidade físico-química de sistemas poliméricos nanoparticulados para administração de fármacos

Paclitaxel‐Initiated, Controlled Polymerization of Lactide for the Formulation of Polymeric Nanoparticulate Delivery Vehicles

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