Structural characterization of organized systems of polysaccharides and phospholipids by light scattering spectroscopy and electron microscopy

Santos, Nuno C.; Sousa, Adelaide M.A.; Betbeder, Didier; Prieto, Manuel; Castanho, Miguel A. R. B.

doi:10.1016/s0008-6215(97)00025-6

Cited by 7 publications

(3 citation statements)

References 30 publications

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“…Alguns destes métodos de modificação já se mostraram úteis na preparação de transportadores para aplicações biomédicas, nomeadamente terapia génica, quimioterapia e direccionamento de lipossomas para células, orgãos ou tecidos específicos 65 . As várias aproximações possíveis à elaboração de sistemas de vesículas lipídicas estabilizadas têm sido descritas em diversos artigos de revisão, alguns dos quais centrados em aproximações especí-ficas 43,50,64,65,[73][74][75][76][77][78][79][80] .…”

Section: Vesículas Lipídicas Estabilizadasunclassified

Lipossomas: a bala mágica acertou?

Santos¹,

Castanho²

2002

Quím. Nova

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Recebido em 15/2/02; aceito em 10/4/02 LIPOSOMES: HAS THE MAGIC BULLET HIT THE TARGET? Efficient drug delivery systems are as important as drug themselves. A powerful drug unable to reach the target cell is useless in practice. Ehrlich's Magic Bullet was the first carrier system to be proposed. The evolution in this domain has been quite slow as the natural mechanisms of mammals against foreign products are hard to overcome. However, lipid-based systems (liposomes and related vesicles) have attained reasonable success. The basic preparations and structural features of liposomes and related vesicles as well as their applications are addressed from the chemist's and biochemist's point of view.Keywords: liposome; vesicle; drug delivery. INTRODUÇÃOAo longo dos tempos, a utilização da maioria dos compostos terapêuticos tem sido sempre limitada pela impossibilidade de aumento da sua dosagem. A retenção ou degradação do agente terapêutico, baixa solubilidade e, em especial, os efeitos colaterais perniciosos inerentes à sua utilização em concentrações elevadas, tornam muitas vezes difícil a utilização da dosagem necessária para que este cumpra a sua função. Este problema levou a que, durante o século XX, e em especial no decorrer das últimas décadas, tenha sido levado a cabo um grande esforço no sentido de desenvolver um sistema capaz de transportar um composto terapêutico (drogas, em especial as dirigidas a tumores, antibióticos, enzimas, hormonas, agentes quelantes ou compostos modificadores da célula) até um alvo específico (órgão, tecido ou célula).A primeira proposta de um sistema direccionado de transporte de fármacos data do início do século XX 1 , quando Paul Ehrlich propôs o seu modelo, que ficou conhecido por "Bala Mágica de Ehrlich" (Ehrlich's Magic Bullet). Neste modelo, o fármaco é ligado ao transportador direccionado, e idealmente exibirá a sua actividade farmacológica apenas no tecido alvo (mecanismos de especificidade, como a ligação entre antigénio e anticorpo, eram já conhecidos). Assim, os efeitos indesejáveis resultantes da sua acção em outros tecidos são largamente diminuídos, enquanto o aumento da eficiên-cia permite o decréscimo da dose administrada. Porém, por mais atractivos e simples que possam parecer os conceitos de Ehrlich, são muito poucos os sucessos até agora obtidos 2,3 . As primeiras tentativas para a obtenção de um sistema transportador eficaz tiveram como base o encapsulamento das biomoléculas a transportar em vesículas de nylon e outros polímeros sintéticos [4][5][6] . Contudo, esta abordagem mostrou-se totalmente inadequada, visto estas vesículas de material artificial se acumularem no organismo.O primeiro grande passo em frente nesta área deu-se em 1965, com a publicação por Alec Bangham e colaboradores de um trabalho de investigação fundamental acerca da difusão de iões através de membranas lipídicas artificiais, embora sem qualquer ligação imediata aos estudos de sistemas transportadores de fármacos 7 . Neste trabalho foi feita a caracterização de um sistema de vesículas fosfolip...

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Section: Vesículas Lipídicas Estabilizadasunclassified

Lipossomas: a bala mágica acertou?

Santos¹,

Castanho²

2002

Quím. Nova

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“…Although frequently overlooked, light scattering spectroscopy is one of the possible noninvasive approaches to study membrane-peptide interactions. Techniques based on light scattering theory have been used to determine the weight-averaged molecular weight (M w ), size [given by the value of the intensity-weighted mean hydrodynamic size (R H )], and aggregation behavior of peptide in solution, either alone or interacting with other particles, such as lipid vesicles [15,16]. The most frequently used techniques based on light scattering are the so-called intensity or static light scattering (SLS) and dynamic light scattering (DLS).…”

Section: Introductionmentioning

confidence: 99%

What can light scattering spectroscopy do for membrane‐active peptide studies?

Domingues

Santiago

Castanho

et al. 2008

Journal of Peptide Science

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Highly charged peptides are important components of the immune system and belong to an important family of antibiotics. Although their therapeutic activity is known, most of the molecular level mechanisms are controversial. A wide variety of different approaches are usually applied to understand their mechanisms, but light scattering techniques are frequently overlooked. Yet, light scattering is a noninvasive technique that allows insights both on the peptide mechanism of action as well as on the development of new antibiotics. Dynamic light scattering (DLS) and static light scattering (SLS) are used to measure the aggregation process of lipid vesicles upon addition of peptides and molecular properties (shape, molecular weight). The high charge of these peptides allows electrostatic attraction toward charged lipid vesicles, which is studied by zeta potential (ζ -potential) measurements.

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“… − on various supported spherical bilayers (with silica, , poly(styrene), − poly(methyl methacrylate) 52 cores). The lipid coating around the particles was investigated in terms of adsorption isotherm, size, surface charge potential, colloidal stability, and biomolecular recognition. , Finally, the Biovector Therapeutics company − produced a system based on cross-linked polysaccharidic cationic nanoparticles (∼60 nm) surrounded by a mixture of phospholipids and cholesterol, designed for vaccines and drug delivery. These structures have been shown to be well tolerated by animals after intranasal administration …”

Section: Introductionmentioning

confidence: 99%

Physicochemical and Interfacial Investigation of Lipid/Polymer Particle Assemblies

et al. 2005

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A model study was investigated to develop colloidal supramolecular assemblies consisting of particles coated with lipid layers. The interactions between monodisperse sulfate-charged poly(styrene) submicrometer particles and zwitterionic/cationic lipid vesicles composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-3-trimethylammonium propane were considered. The influence of relevant experimental parameters on the final associations was examined by quasi-elastic light scattering to point out some new phenomena occurring in these colloidal systems. The major role of electrostatic interactions as driving forces to control the organization between cationic lipids and oppositely charged poly(styrene) particles was clearly evident, whereas this influence was less pronounced when considering the zwitterionic lipids. The characterization of these original complex assemblies was completed by a thorough study of the surface modification. The combination of zeta potential measurements, X-ray photoelectron spectroscopy analyses, and microscopy observations proved that the envisioned model can really correspond to polymer particles surrounded by lipids.

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Structural characterization of organized systems of polysaccharides and phospholipids by light scattering spectroscopy and electron microscopy

Cited by 7 publications

References 30 publications

Lipossomas: a bala mágica acertou?

Lipossomas: a bala mágica acertou?

What can light scattering spectroscopy do for membrane‐active peptide studies?

Physicochemical and Interfacial Investigation of Lipid/Polymer Particle Assemblies

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