Pharmaceutical emulsions: a new approach for gene therapy

Veríssimo, Lourena Mafra; Agnez-Lima, Lucymara Fassarella; Egito, Lucila Carmem Monte; Oliveira, Anselmo Gomes de; Egito, Eryvaldo Sócrates Tabosa do

doi:10.3109/10611860903434019

Cited by 23 publications

(21 citation statements)

References 89 publications

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“…Estes sistemas não serão abordados neste artigo, mas têm sido recentemente revisados. 49,50 A adição de polímeros hidrofílicos às nanoemulsões, como Tween 80, ou derivados de polietilenoglicol (PEG) ligados covalentemente à fosfatidiletanolamina, pode resultar no prolongamento do tempo de circulação das emulsões na corrente sanguínea e menor biodistribuição, o que pode ser atribuído à barreira estérica formada pelos polímeros em relação às proteínas.…”

Section: 26unclassified

Nanoemulsões como sistemas de liberação parenteral de fármacos

Bruxel¹,

Laux²,

Wild³

et al. 2012

Quím. Nova

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Recebido em 20/10/11; aceito em 29/3/12; publicado na web em 3/7/12 NANOEMULSIONS AS PARENTERAL DRUG DELIVERY SYSTEMS. Lipid nanoemulsions have recently been proposed as parenteral delivery systems for poorly-soluble drugs. These systems consist of nanoscale oil/water dispersions stabilized by an appropriate surfactant system in which the drug is incorporated into the oil core and/or adsorbed at the interface. This article reviews technological aspects of such nanosystems, including their composition, preparation methods, and physicochemical properties. From this review, it was possible to identify five groups of nanoemulsions based on their composition. Biopharmaceutical aspects of formulations containing some commercially available drugs (diazepam, propofol, dexamethasone, etomidate, flurbiprofen and prostaglandin E1) were then discussed.Keywords: emulsion; parenteral; drug. INTRODUÇÃOA solubilização de fármacos de reduzida hidrossolubilidade visando sua administração parenteral representa um grande desafio na área de desenvolvimento de medicamentos. Diversas estratégias são descritas na literatura para esta finalidade, incluindo a modificação do pH do veículo, a adição de cossolventes ou, ainda, a formação de complexos de inclusão com ciclodextrinas.1 Entretanto, limitações relacionadas à biocompatibilidade dos adjuvantes empregados, aos relatos de dor e de possível precipitação dos fármacos durante a administração podem ser considerados como fatores limitantes do uso destas abordagens. Neste contexto, sistemas nanoestruturados têm se mostrado promissores. Nanoemulsões lipídicas óleo em água têm sido empregadas há mais de 40 anos como fonte de calorias e ácidos graxos essenciais 2 e, mais recentemente, como sistemas de liberação de fármacos. A biocompatibilidade das matérias-primas empregadas para a sua obtenção (óleos de origem natural ou semissintética e fosfolipídeos) torna estes sistemas uma alternativa promissora para a administração de diversos tipos de moléculas.3 Nanoemulsões podem ser definidas como sistemas heterogêneos nos quais um líquido (a fase interna) é disperso em outro (a fase externa) na forma de gotículas, na presença de um agente emulsionante. Suas propriedades físico--químicas, influenciadas pela composição quali-e quantitativa e pelas condições de preparação, devem ser estritamente controladas, visando a administração por via parenteral e a estabilidade do sistema. 4,5 Existem na literatura algumas inconsistências relacionadas aos conceitos de nanoemulsões em relação às microemulsões. Apesar destes sistemas poderem apresentar características estruturais e visuais semelhantes em determinadas condições, diferenciam-se quanto a estabilidade termodinâmica. Contrariamente às nanoemulsões, as microemulsões são sistemas termodinamicamente estáveis. Entretanto, podem apresentar limitações para administração por via parenteral, pois suas propriedades são fortemente afetadas por alterações de temperatura e/ou diluições. Apesar da nomenclatura empregada, microemulsões apresentam geralmente tamanho...

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Section: 26unclassified

Nanoemulsões como sistemas de liberação parenteral de fármacos

Bruxel¹,

Laux²,

Wild³

et al. 2012

Quím. Nova

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“…13 Cationic nanoemulsions have been more recently considered as a potential system for nucleic acid delivery. 14 The interest in these systems is justified by the fact that they are biocompatible and able to form complexes with DNA, protecting them from enzymatic degradation. 7 Other practical advantages include ease of production and the potential for repeated administration.…”

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Influence of phospholipid composition on cationic emulsions/DNA complexes: physicochemical properties, cytotoxicity, and transfection on Hep G2 cells

Fraga¹,

Bruxel²,

Lagranha³

et al. 2011

IJN

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Background Cationic nanoemulsions have been recently considered as potential delivery systems for nucleic acids. This study reports the influence of phospholipids on the properties of cationic nanoemulsions/DNA plasmid complexes. Methods Nanoemulsions composed of medium-chain triglycerides, stearylamine, egg lecithin or isolated phospholipids, ie, DSPC, DOPC, DSPE, or DOPE, glycerol, and water were prepared by spontaneous emulsification. Gene transfer to Hep G2 cells was analyzed using real-time polymerase chain reaction. Results The procedure resulted in monodispersed nanoemulsions with a droplet size and zeta potential of approximately 250 nm and +50 mV, respectively. The complexation of cationic nanoemulsions with DNA plasmid, analyzed by agarose gel retardation assay, was complete when the complex was obtained at a charge ratio of ≥1.0. In these conditions, the complexes were protected from enzymatic degradation by DNase I. The cytotoxicity of the complexes in Hep G2 cells, evaluated by MTT assay, showed that an increasing number of complexes led to progressive toxicity. Higher amounts of reporter DNA were detected for the formulation obtained with the DSPC phospholipid. Complexes containing DSPC and DSPE phospholipids, which have high phase transition temperatures, were less toxic in comparison with the formulations obtained with lecithin, DOPC, and DOPE. Conclusion The results show the effect of the DNA/nanoemulsion complexes composition on the toxicity and transfection results.

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“…65 The colipid DOPE is extensively used because of its fusogenic properties to improve the ability of emulsions and cationic liposomes to transfect cells. 66 This is partially explained by the fact that the amine group of DOPE interacts with DNA phosphate groups, thus weakening the binding affinity between cationic lipids and DNA. Cationic nanoemulsions have been described as a promising strategy to improve transfection of nucleic acids to mammalian cells, protecting them against nuclease attack.…”

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“…The physical characteristics and serum-resistant properties of the nanoemulsion complexes indicate that cationic nanoemulsions could be a more efficient carrier system for nucleic acids and/or immunogene delivery than liposomes. 66 The fact that transfection is efficient in the presence of serum is an important advantage. One of the reasons for the serum-resistant properties of the cationic lipid nanoemulsion may be the stability of the nanoemulsion/nucleic acid complex.…”

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Development of nucleic acid vaccines: use of self-amplifying RNA in lipid nanoparticles

Rodríguez-Gascón¹,

Pozo-Rodríguez²,

Solinís³

2014

IJN

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Self-amplifying RNA or RNA replicon is a form of nucleic acid-based vaccine derived from either positive-strand or negative-strand RNA viruses. The gene sequences encoding structural proteins in these RNA viruses are replaced by mRNA encoding antigens of interest as well as by RNA polymerase for replication and transcription. This kind of vaccine has been successfully assayed with many different antigens as vaccines candidates, and has been shown to be potent in several animal species, including mice, nonhuman primates, and humans. A key challenge to realizing the broad potential of self-amplifying vaccines is the need for safe and effective delivery methods. Ideally, an RNA nanocarrier should provide protection from blood nucleases and extended blood circulation, which ultimately would increase the possibility of reaching the target tissue. The delivery system must then be internalized by the target cell and, upon receptor-mediated endocytosis, must be able to escape from the endosomal compartment into the cell cytoplasm, where the RNA machinery is located, while avoiding degradation by lysosomal enzymes. Further, delivery systems for systemic administration ought to be well tolerated upon administration. They should be safe, enabling the multiadministration treatment modalities required for improved clinical outcomes and, from a developmental point of view, production of large batches with reproducible specifications is also desirable. In this review, the concept of self-amplifying RNA vaccines and the most promising lipid-based delivery systems are discussed.

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Pharmaceutical emulsions: a new approach for gene therapy

Cited by 23 publications

References 89 publications

Nanoemulsões como sistemas de liberação parenteral de fármacos

Nanoemulsões como sistemas de liberação parenteral de fármacos

Influence of phospholipid composition on cationic emulsions/DNA complexes: physicochemical properties, cytotoxicity, and transfection on Hep G2 cells

Development of nucleic acid vaccines: use of self-amplifying RNA in lipid nanoparticles

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