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Jaeghere, Fanny De; Allémann, Éric; Leroux, Jean‐Christophe; Stevels, Willem M.; Feijén, Jan; Doelker, Éric; Gurny, Robert

doi:10.1023/a:1018826103261

Cited by 145 publications

(41 citation statements)

References 18 publications

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“…A liofilização consiste na remoção da água (gelo) através de sublimação [121][122][123] e tem sido amplamente empregada para a secagem de suspensões de nanoesferas 38,40,41,89,[124][125][126] . Entretanto, no caso das suspensões de nanocápsulas, poucos trabalhos, utilizando esta operação, têm sido desenvolvidos 87,99,127,128 .…”

Section: Liofilizados De Nanopartículasunclassified

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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Section: Liofilizados De Nanopartículasunclassified

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

et al. 2003

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“…Most other papers [13][14][15][16] deal with particles coated with copolymers of PEO or PEG, which we believe are not quite as controllable or versatile in their surface composition as the micelles discussed in this work. Some early work by de Jaeghere et al [18] does discuss PLA-PEG copolymers, alone and blended with PLA, but this is restricted to diblock copolymers of relatively narrow size distribution: the PEG surface concentration was varied mainly by blending. A similar, but more extensive study was reported by Gref et al [19] In this study, the authors synthesized diblock copolymers of PEG with PLA (and other polymers), and studied the effects of PEG chain length and PEG content on protein adsorption, and to a more limited extent, uptake by polymorphonuclear leukocyte (PMN) cells (no monocytes).…”

Section: Introductionmentioning

confidence: 99%

Block Copolymer ‘Stealth’ Nanoparticles for Chemotherapy: Interactions with Blood Cells In Vitro

Lwin

Venkatraman

2008

Adv Funct Materials

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Passive targeting is one of the approaches to reduce the side effects in intravenous chemotherapeutic administration. This is usually achieved by using so‐called ‘stealth’ particles as carriers, such that the particles can avoid uptake by cells of the reticulo endothelial system (RES) and thus enhance their blood lifetime. To date, there have been no studies of the contribution of various factors to the uptake of particles by the RES, although there is general agreement that a hydrophilic particle surface is helpful. In this study, data is presented on the effect of particle size and surface chemistry on the uptake by monocyte cell lines, as well as by cells in whole blood. Block copolymers of hydrophilic poly(ethylene glycol) (PEG) and the hydrophobic poly(L‐lactide) (PLA) have been used to study surface concentration and conformation effects. It is found that diblock copolymers, in general, show the best stealth characteristics, although triblocks with PEG segment lengths above a certain value are also comparable. It is also found that the uptake goes through a minimum with respect to particle size. For the first time, a method is presented to evaluate the relative uptake efficiency of various types of blood cells, using flow cytometry. The observations are related to structural features found on the polymers.

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“…Such polymeric micelles would be expected to sequester hydrophobic drugs like Doxorubicin (Dox) into their hydrophobic core, and their PEO outer corona would reduce clearance of the polymeric micelles by the mononuclear phagocytic system (MPS) in vivo [2]. The formation and stability of the PEO-b-poly(NIPAAm-co-HEMAlactate n ) micelles also would depend on their concentration and surrounding temperature, with the polymeric micelles forming at temperatures above the critical micelle temperature (CMT).…”

Section: Introductionmentioning

confidence: 99%

A polymeric micelle system with a hydrolysable segment for drug delivery

Zeng

Pitt²

2006

Journal of Biomaterials Science, Polymer Edition

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A potential anticancer drug delivery polymeric micelle system with an in vitro degradation half-life of about 48 hours that releases its drug upon application of ultrasound was synthesized. This vehicle was composed of an amphiphilic copolymer poly(ethylene oxide)-b-poly(N-isopropylacrylamideco-2-hydroxyethyl methacrylate-lactate n ). The degree of polymerization of lactate side group, n, was 0, 3 or 5. The molar ratio of NIPAAm to HEMA-lactate n to PEO in polymerization was optimized to produce an in vitro polymeric micelle half-life of about 48 hour at 40°C. 1,6-diphenyl-1,3,5-hexatriene (DPH) was used as a fluorescent probe to study the hydrophobicity of the cores of the polymeric micelles. The results showed that the cores of the polymeric micelles were hydrophobic enough to sequester DPH and the anti-cancer drug Doxorubicin (Dox). Dox was encapsulated into the polymeric micelles having molar feed ratio of NIPAAm to HEMA-lactate 3 to PEO equal to 20 : 5 : 1; this drug was released upon the application of low-frequency ultrasound. The Dox release was about 2 % at room temperature and 4 % at body temperature, and the drug returned to the polymeric micelles when insonation ceased.

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Cited by 145 publications

References 18 publications

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

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

Block Copolymer ‘Stealth’ Nanoparticles for Chemotherapy: Interactions with Blood Cells In Vitro

A polymeric micelle system with a hydrolysable segment for drug delivery

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