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Nanoparticles incorporating pH-responsive surfactants as a viable approach to improve the intracellular drug delivery
Nogueira, Daniele R.; Scheeren, Laís E.; Vinardell Martínez-Hidalgo, Ma. Pilar; Mitjans Arnal, Montserrat; Infante Martínez-Pardo, Ma. Rosa; Rolim, Clarice M.B.
Universitat de Barcelona
The pH-responsive delivery systems have brought newadvances in the field of functional nanodevices and might allow more accurate and controllable delivery of specific cargoes, which is expected to result in promising applications in different clinical therapies. Here we describe a family of chitosan TPP (tripolyphosphate) nanoparticles (NPs) for intracellular drug delivery, which were designed using two pH-sensitive amino acid-based surfactants fromthe family Nα,Nε-dioctanoyl lysine as bioactive compounds. Lowand mediummolecularweight chitosan (LMW-CS and MMW-CS, respectively) were used for NP preparation, and it was observed that the size distribution for NPs with LMW-CS were smaller (~168 nm) than that for NPs prepared with MMW-CS (~310 nm). Hemolysis assay demonstrated the pH-dependent biomembrane disruptional capability of the constructed NPs. The nanostructures incorporating the surfactants cause negligible membrane permeabilization at pH 7.4. However, at acidic pH, prevailing in endosomes, membrane-destabilizing activity in an erythrocyte lysis assay became evident. When pH decreased to 6.6 and 5.4, hemolytic capability of chitosan NPs increased along with the raise of concentration. Furthermore, studies with cell culture showed that these pH-responsive NPs displayed low cytotoxic effects against 3T3 fibroblasts. The influence of chitosan molecular weight, chitosan to TPP weight ratio, nanoparticle size and nature of the surfactant counterion on the membrane-disruptive properties of nanoparticleswas discussed in detail. Altogether, the results achieved here showed that by inserting the lysine-based amphiphiles into chitosan NPs, pH-sensitive membranolytic and potentially endosomolytic nanocarriers were developed, which, therefore, demonstrated ideal feasibility for intracellular drug delivery.
Quitosan
Nanopartícules
Agents tensioactius
Sistemes d'alliberament de medicaments
Hemòlisi
Toxicologia
Chitosan
Nanoparticles
Surface active agents
Drug delivery systems
Hemolysis
Toxicology
cc-by-nc-nd (c) Elsevier B.V., 2015
info:eu-repo/semantics/embargoedAccess
http://creativecommons.org/licenses/by-nc-nd/3.0/es
Artículo
info:eu-repo/semantics/acceptedVersion
Elsevier B.V.
         

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Scheeren, Laís E.; Nogueira, Daniele R.; Macedo, Letícia B.; Vinardell Martínez-Hidalgo, Ma. Pilar; Mitjans Arnal, Montserrat; Infante Martínez-Pardo, Ma. Rosa; Rolim, Clarice M.B.
Nogueira, Daniele R.; Scheeren, Laís E.; Macedo, Letícia B.; Marcolino, Ana Isa P.; Mitjans Arnal, Montserrat; Vinardell Martínez-Hidalgo, Ma. Pilar; Infante Martínez-Pardo, Ma. Rosa; Farooqi, Ammad A.; Rolim, Clarice M.B.
Nogueira D.R.; Macedo, Letícia B.; Scheeren, Laís E.; Mitjans Arnal, Montserrat; Infante Martínez-Pardo, Ma. Rosa; Rolim, Clarice M.B.; Vinardell Martínez-Hidalgo, Ma. Pilar
Nogueira, Daniele R.; Mitjans Arnal, Montserrat; Rolim, Clarice M.B.; Vinardell Martínez-Hidalgo, Ma. Pilar
Nogueira, Daniele R.; Mitjans Arnal, Montserrat; Infante Martínez-Pardo, Ma. Rosa; Vinardell Martínez-Hidalgo, Ma. Pilar