Association with Amino Acids Does Not Enhance Efficacy of Polymerized Liposomes As a System for Lung Gene Delivery

Abstract

Development of improved drug and gene delivery systems directly into the lungs is highly desirable given the important burden of respiratory diseases. We aimed to evaluate the safety and efficacy of liposomes composed of photopolymerized lipids [1,2-bis-(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine] associated with amino acids as vectors for gene delivery into the lungs of healthy animals. Lipopolymer vesicles, in particular, are more stable than other types of liposomes. In this study, lipopolymers were associated with l-arginine, l-tryptophan, or l-cysteine. We hypothesized that the addition of these amino acids would enhance the efficacy of gene delivery to the lungs by the lipopolymers. l-Arginine showed the highest association efficiency due to its positive charge and better surface interactions. None of the formulations caused inflammation or altered lung mechanics, suggesting that these lipopolymers can be safely administered as aerosols. All formulations were able to induce eGFP mRNA expression in lung tissue, but the addition of amino acids reduced delivery efficacy when compared with the simple lipopolymer particle. These results indicate that this system could be further explored for gene or drug delivery targeting lung diseases.

Diacetylenic lipids in the design of stable lipopolymers able to complex and protect plasmid DNA

“…It has been previously reported that polymeric liposomes have little interaction with DNA [ 23 ]. Recently, it has been shown that the mixture of the polymerizable diacetylenic lipid 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC 8,9 PC) and the lipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) (1:1) itself has the ability to transfect cells in vivo in mice [ 45 ] after being administered intratracheally. These results give the first indication that lipopolymers formulated with the diacetylenic lipid DC 8,9 PC might be used for in vivo DNA delivery.…”

Efectos del entrenamiento de intervalos de alta intensidad en altitud simulada. Revisión sistemática

“…En lo que se refiere a las adaptaciones cardiovasculares, se manifiestan después de dos a cuatro semanas de comenzar un entrenamiento, generando incremento en el gasto cardiaco máximo, que se encuentra correlacionado positivamente con las adaptaciones hematológicas [51]. Se evidencia que tanto el volumen de plasma como la sangre aumentan considerablemente [52] y la frecuencia cardiaca disminuye [53].…”

Lipopolymers and lipids from lung surfactants in association with N-acetyl-l-cysteine: Characterization and cytotoxicity

“…Liposomes as multilamellar vesicles (MLVs) were obtained by the dehydration-rehydration method, as previously described (Bandeira et al, 2016;Bangham, 1972;Julieta et al, 2013;Marsanasco, Márquez, Wagner, del V. Alonso, & Chiaramoni, 2011) Briefly, 10 mg of total lipids were dissolved in 0.2 mL of methanol. Then, the solvent was evaporated, and the film was resuspended in 1 mL of Phosphate Saline Buffer, pH 7.4 (PBS).…”