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https://hdl.handle.net/10316/5766
Título: | On the formulation of pH-sensitive liposomes with long circulation times | Autor: | Simões, Sérgio Moreira, João Nuno Fonseca, Cristina Düzgünes, Nejat Pedroso de Lima, Maria C. |
Palavras-chave: | Liposomes; Phosphatidylethanolamine, cholesteryl hemisuccinate; Sterically stabilized liposomes; Poly(ethylene glycol); Prolonged circulation; Endocytosis; Low pH compartment; Intracellular delivery; Neoplastic drugs; Gene delivery; Antisense oligonucleotides; Ribozymes | Data: | 2004 | Citação: | Advanced Drug Delivery Reviews. 56:7 (2004) 947-965 | Resumo: | Strategies used to enhance liposome-mediated drug delivery in vivo include the enhancement of stability and circulation time in the bloodstream, targeting to specific tissues or cells, and facilitation of intracytoplasmic delivery. pH-sensitive liposomes have been developed to mediate the introduction of highly hydrophilic molecules or macromolecules into the cytoplasm. These liposomes destabilize under acidic conditions found in the endocytotic pathway, and usually contain phosphatidylethanolamine (PE) and titratable stabilizing amphiphiles. Formulations without PE have also been developed. Encapsulated compounds are thought to be transported into the cytoplasm through destabilization of or fusion with the endosome membrane. Incorporation of a low mole percentage of poly(ethylene glycol) (PEG)-conjugated lipids into pH-sensitive liposomes confers prolonged circulation times to these liposomes, which are otherwise cleared rapidly. While the incorporation of PEG-lipids reduces the pH-dependent release of encapsulated fluorescent markers in vitro, it does not hinder the cytoplasmic delivery of the markers per cell-associated liposome. This suggests that intracellular delivery is not dictated simply by the destabilization of the liposomes. Antibodies or ligands to cell surface receptors can be coupled to pH-sensitive or sterically stabilized pH-sensitive liposomes for targeting. pH-sensitive liposomes have been used to deliver anticancer drugs, antibiotics, antisense oligonucleotides, ribozymes, plasmids, proteins and peptides to cells in culture or in vivo. | URI: | https://hdl.handle.net/10316/5766 | DOI: | 10.1016/j.addr.2003.10.038 | Direitos: | openAccess |
Aparece nas coleções: | FFUC- Artigos em Revistas Internacionais |
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fileb48b9f70f57842c9b4d9aafbc4d4650f.pdf | 515.62 kB | Adobe PDF | Ver/Abrir |
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