Formulation Strategies, Characterization, and <i>In Vitro</i> Evaluation of Lecithin-Based Nanoparticles for siRNA Delivery

Pérez, Sebastián E.; Gándola, Yamila B.; Carlucci, Adriana; González, Lorena; Turyn, Daniel; Bregni, Carlos

doi:10.1155/2012/986265

Cited by 9 publications

(14 citation statements)

References 31 publications

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“…To determine oligonucleotide internalization, transfection experiments were performed either in absence or presence of serum and after a 24-hour incubation period [7]. That study suggested that lecithin-based delivery systems might represent feasible novel formulations for anticancer gene therapies.…”

Section: Resultsmentioning

confidence: 99%

“…The main differences between both PC preparations is the charge associated with the particles (zeta potential) (Table 1) and the final adopted form [7], while the size of the particles did not show important differences (Table 1). The nanoparticles were in the range of 180–250 nm for all the studied conditions (Table 1).…”

Section: Discussionmentioning

confidence: 99%

“…Actually, nanoparticles designed from lecithin-in-water emulsions were successfully used to deliver docetaxel to tumor cells in vitro and even in a tumor model in mice [ 6 ]. Moreover, lecithin-based nanoparticles have demonstrated to deliver siRNA to breast cancer cells [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

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Mitogenic Effects of Phosphatidylcholine Nanoparticles on MCF-7 Breast Cancer Cells

Gándola

Pérez

Irene

et al. 2014

BioMed Research International

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Lecithins, mainly composed of the phospholipids phosphatidylcholines (PC), have many different uses in the pharmaceutical and clinical field. PC are involved in structural and biological functions as membrane trafficking processes and cellular signaling. Considering the increasing applications of lecithin-based nanosystems for the delivery of therapeutic agents, the aim of the present work was to determine the effects of phosphatidylcholine nanoparticles over breast cancer cellular proliferation and signaling. PC dispersions at 0.01 and 0.1% (w/v) prepared in buffer pH 7.0 and 5.0 were studied in the MCF-7 breast cancer cell line. Neutral 0.1% PC-derived nanoparticles induced the activation of the MEK-ERK1/2 pathway, increased cell viability and induced a 1.2 fold raise in proliferation. These biological effects correlated with the increase of epidermal growth factor receptor (EGFR) content and its altered cellular localization. Results suggest that nanoparticles derived from PC dispersion prepared in buffer pH 7.0 may induce physicochemical changes in the plasma membrane of cancer cells which may affect EGFR cellular localization and/or activity, increasing activation of the MEK-ERK1/2 pathway and inducing proliferation. Results from the present study suggest that possible biological effects of delivery systems based on lecithin nanoparticles should be taken into account in pharmaceutical formulation design.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Mitogenic Effects of Phosphatidylcholine Nanoparticles on MCF-7 Breast Cancer Cells

Gándola

Pérez

Irene

et al. 2014

BioMed Research International

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“…Lecithin is a phospholipid which is well reported for its long circulation time, colloidal stability, and non-cytotoxicity. 28 The GNPs were compared with standard CT contrast, that is, iodine, for in vivo application ( Figure 1). …”

Section: Introductionmentioning

confidence: 99%

Novel route synthesis of porous and solid gold nanoparticles for investigating their comparative performance as contrast agent in computed tomography scan and effect on liver and kidney function

Aziz¹,

Ihsan²,

Nazir³

et al. 2017

IJN

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Gold nanoparticles (GNPs) with dimension in the range of 1–100 nm have a prominent role in a number of biomedical applications like imaging, drug delivery, and cancer therapy owing to their unique optical features and biocompatibility. In this work, we report a novel technique for the synthesis of two types of GNPs namely porous gold nanoparticles (PGNPs) and solid gold nanoparticles (SGNPs). PGNPs of size 35 nm were fabricated by reduction of gold (III) solution with lecithin followed by addition of L-ascorbic acid and tri-sodium citrate, whereas SGNPs with a dimension of 28 nm were prepared by reflux method using lecithin as a single reducing agent. Comparative studies using PGNPs (λ max 560 nm) and SGNPs (λ max 548 nm) were conducted for evaluating their use as a contrast agent. These studies reveled that in direct computed tomography scan, PGNPs exhibited brighter contrast (45 HU) than SGNPs (26 HU). To investigate the effect of PGNPs and SGNPs on the liver and kidney profile, male rabbits were intravenously injected with an equal dose of 1 mg/kg weight of PGNPs and SGNPs. The effect on biochemical parameters was evaluated 72 hours after intravenous (IV) injection including liver function profile, renal (kidney) function biomarker, random blood glucose value, and cholesterol level. During one comparison of contrast in CT scan, PGNPs showed significantly enhanced contrast in whole-rabbit and organ CT scan as compared to SGNPs 6 hours after injection. Our findings suggested that the novel PGNPs enhance CT scan image with higher efficacy as compared to SGNPs. The results showed that IV administration of synthesized PGNPs increases the levels of aspartate aminotransferase (AST), alkaline phosphate (ALP), serum creatinine, and blood glucose, whereas that of SGNPs increases the levels of AST, ALP, and blood glucose.

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“…The rate of viability was assessed using a WST reduction assay. 34 No cytotoxicity was evident over the concentration range of siRNA used (1-1,000 nM), corresponding to a DODMA concentration range of 0.24-240 nM ( Figure S3). …”

Section: Cytotoxicity Of Lipoplexes and Lnpsmentioning

confidence: 99%

Effect of the nanoformulation of siRNA-lipid assemblies on their cellular uptake and immune stimulation

Kubota¹,

Onishi²,

Sawaki³

et al. 2017

IJN

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Two lipid-based nanoformulations have been used to date in clinical studies: lipoplexes and lipid nanoparticles (LNPs). In this study, we prepared small interfering RNA (siRNA)-loaded carriers using lipid components of the same composition to form molecular assemblies of differing structures, and evaluated the impact of structure on cellular uptake and immune stimulation. Lipoplexes are electrostatic complexes formed by mixing preformed cationic lipid liposomes with anionic siRNA in an aqueous environment, whereas LNPs are nanoparticles embedding siRNA prepared by mixing an alcoholic lipid solution with an aqueous siRNA solution in one step. Although the physicochemical properties of lipoplexes and LNPs were similar except for small increases in apparent size of lipoplexes and zeta potential of LNPs, siRNA uptake efficiency of LNPs was significantly higher than that of lipoplexes. Furthermore, in the case of LNPs, both siRNA and lipid were effectively incorporated into cells in a co-assembled state; however, in the case of lipoplexes, the amount of siRNA internalized into cells was small in comparison with lipid. siRNAs in lipoplexes were thought to be more likely to localize on the particle surface and thereby undergo dissociation into the medium. Inflammatory cytokine responses also appeared to differ between lipoplexes and LNPs. For tumor necrosis factor-α, release was mainly caused by siRNA. On the other hand, the release of interleukin-1β was mainly due to the cationic nature of particles. LNPs released lower amounts of tumor necrosis factor-α and interleukin-1β than lipoplexes and were thus considered to be better tolerated with respect to cytokine release. In conclusion, siRNA-loaded nanoformulations effect their cellular uptake and immune stimulation in a manner that depends on the structure of the molecular assembly; therefore, nanoformulations should be optimized before extending studies into the in vivo environment.

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Formulation Strategies, Characterization, and In Vitro Evaluation of Lecithin-Based Nanoparticles for siRNA Delivery

Cited by 9 publications

References 31 publications

Mitogenic Effects of Phosphatidylcholine Nanoparticles on MCF-7 Breast Cancer Cells

Mitogenic Effects of Phosphatidylcholine Nanoparticles on MCF-7 Breast Cancer Cells

Novel route synthesis of porous and solid gold nanoparticles for investigating their comparative performance as contrast agent in computed tomography scan and effect on liver and kidney function

Effect of the nanoformulation of siRNA-lipid assemblies on their cellular uptake and immune stimulation

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