Efficient Gene Delivery by EGF-Lipoplexes
            <i>In Vitro</i>
            and
            <i>In Vivo</i>

Buñuales, María; Düzgüneş, Nejat; Zalba, Sara; Garrido, María J.; Ilarduya, Conchita Tros de

doi:10.2217/nnm.10.100

Cited by 29 publications

(20 citation statements)

References 28 publications

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“…It has also been suggested that reduction in particle size results from an effect of osmotic stress produced by concentration and pH gradients. However, the size of liposomes prepared by (NH 4 ) 2 SO 4 gradient was in the range of 100 and 250 nm, which puts them under the category of SUVs as reported by others [31]. The SUV like size distribution of the liposomes suggest that hydration followed by sonication can be used for preparation of SUVs.…”

Section: Resultsmentioning

confidence: 89%

Liposomal fasudil, a rho-kinase inhibitor, for prolonged pulmonary preferential vasodilation in pulmonary arterial hypertension

Gupta

Shaik

et al. 2013

Journal of Controlled Release

109

133

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Current pharmacological interventions for pulmonary arterial hypertension (PAH) require continuous infusions, multiple inhalations, or oral administration of drugs that act on various pathways involved in the pathogenesis of PAH. However, invasive methods of administration, short duration of action, and lack of pulmonary selectivity result in noncompliance and poor patient outcomes. In this study, we tested the hypothesis that encapsulation of an investigational anti-PAH molecule fasudil (HA-1077), a Rho-kinase inhibitor, into liposomal vesicles results in prolonged vasodilation in distal pulmonary arterioles. Liposomes were prepared by hydration and extrusion method and fasudil was loaded by ammonium sulfate-induced transmembrane electrochemical gradient. Liposomes were then characterized for various physicochemical properties. Optimized formulations were tested for pulmonary absorption and their pharmacological efficacy in a monocrotaline (MCT) induced rat model of PAH. The entrapment efficiency of optimized liposomal fasudil formulations was between 68.1±0.8% and 73.6±2.3%, and the cumulative release at 37°C was 98–99% over a period of 5 days. Compared to intravenous (IV) fasudil, a ~10 fold increase in the terminal plasma half-life was observed when liposomal fasudil was administered as aerosols. The t1/2 of IV fasudil was 0.39±0.12 h. and when given as liposomes via pulmonary route, the t1/2 extended to 4.71±0.72 h. One h after intratracheal instillation of liposomal fasudil, mean pulmonary arterial pressure (MPAP) was reduced by 37.6±5.7% and continued to decrease for about 3 h, suggesting that liposomal formulations produced pulmonary preferential vasodilation in MCT induced PAH rats. Overall, this study established the proof-of-principle that aerosolized liposomal fasudil is a feasible option for a non-invasive, controlled release and pulmonary preferential treatment of PAH.

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Section: Resultsmentioning

confidence: 89%

Liposomal fasudil, a rho-kinase inhibitor, for prolonged pulmonary preferential vasodilation in pulmonary arterial hypertension

Gupta

Shaik

et al. 2013

Journal of Controlled Release

109

133

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“…Recent studies have revealed that recombinant full-length EGF could be coupled to gene and drug delivery systems providing their efficient and fast receptor-mediated endocytosis (de Bruin et al, 2007;Buñuales et al, 2011). However, EGF could also trigger EGFR signaling activation, thus promote tumor cell survival and growth, and peptide GE11 based EGFR-binding results in clathrin-mediated endocytosis without induction of EGFR signaling (Mickler et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

EGFR-targeted poly(ethylene glycol)-distearoylphosphatidylethanolamine micelle loaded with paclitaxel for laryngeal cancer: preparation, characterization andin vitroevaluation

et al. 2014

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The objective of this study was to evaluate the potential of using polymeric micelles modified with a peptide (termed GE11) ligand of epidermal growth factor receptor as the targeted carriers to achieve increased accumulation in laryngeal cancer and enhanced intracellular delivery for the encapsulated anticancer drugs. Poly (ethylene glycol)-distearoylphosphatidylethanolamine (PEG-DSPE) micelles containing paclitaxel were prepared via film-hydration method followed by investigation of in vitro release of paclitaxel in phosphate-buffered saline. The average size of GE11-PEG-DSPE/paclitaxel micelle and mPEG-DSPE/paclitaxel were 35 ± 2.8 nm [the polydispersity index (PDI) ¼ 0.207] and 28 ± 2.1 nm (PDI ¼ 0.154), respectively. Micelles with or without GE11-modified had similar physicochemical properties. Transmission electron microscopy showed that the micelles were homogeneous and spherical in shape. Encapsulation efficiency and drug loading of the micelle were 74.11 ± 3.89% and 3.58 ± 2.82%, respectively. The in vitro targeting characteristic of GE11-modified micelles was investigated by observing the level of cellular uptake of fluorescent coumarin-6-loaded micelles on EGFR overexpressed human laryngeal cancer cell line Hep-2 and EGFR low-expressed human leukemic cell line U-937. Hep-2 cell proliferation was significantly inhibited by GE11-PEG-DSPE/paclitaxel micelle compared to mPEG-DSPE/paclitaxel micelle and Taxol in vitro. Our results suggested that GE11-PEG-DSPE micelle could be a promising strategy for enhancing paclitaxel's chemotherapeutic effects on EGFR over-expressed cancer cells.

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“…The surfactant with the longer, 2,8‐dioxanonane spacer displayed better complexing properties, because partial complexation appeared at p / n= 2 and the entire DNA portion was in a stable complex with a higher surfactant content. Lack of unbound DNA is an important factor that translates directly into the transfection efficiency, because the “naked” nucleic acid is instantly degraded by nucleases; for example, plasmid DNA is digested within the first few minutes by DNase I …”

Section: Resultsmentioning

confidence: 99%

“…Lack of unbound DNA is an important factor that translates directly into the transfection efficiency,b ecause the "naked" nucleic acid is instantly degraded by nucleases; [18] for example, plasmid DNA is digestedw ithin the first few minutes by DNase I. [19] The outcomeo ft he electrophoretic analysisf or systems with RNA and IMI_Gly_n2_C12 andI MI_Gly_n5_C12 is presented in Figure 1(c) and 1(d), respectively.The results are identical to that obtainedf or systems with the DNA duplex;t hat is, the partial complexation of RNA is visible at p/n = 3i nt he case of the 2,5-dioxahexane spacer surfactant anda tp/n = 2f or the 2,8-dioxanonane spacersurfactant. Higher p/n ratios led to successfulc omplex formation and the mobility of the nucleic acid was completely suppressed.…”

Section: Resultsmentioning

confidence: 99%

Dicationic Surfactants with Glycine Counter Ions for Oligonucleotide Transportation

2016

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Gemini surfactants are good candidates to bind, protect, and deliver nucleic acids. Herein, the concept of amino acids (namely glycine) as counter ions of gemini surfactants for gene therapy application was explored. This study was conducted on DNA and RNA oligomers and two quaternary bis-imidazolium salts, having 2,5-dioxahexane and 2,8-dioxanonane spacer groups. The toxicity level of surfactants was assessed by an MTT assay, and their ability to bind nucleic acids was tested through electrophoresis. The nucleic acid conformation was established based on circular dichroism and infrared spectroscopic analyses. The structures of the formed complexes were characterized by small-angle scattering of synchrotron radiation. Both studied surfactants appear to be suitable for gene therapy; however, although they vary by only three methylene groups in the spacer, they differ in binding ability and toxicity. The tested oligonucleotides maintained their native conformations upon surfactant addition and the studied lipoplexes formed a variety of structures. In systems based on a 2,5-dioxahexane spacer, a hexagonal phase was observed for DNA-surfactant complexes and a micellar phase was dominant with RNA. For the surfactant with a 2,8-dioxanonane spacer group, the primitive cubic phase prevailed.

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Efficient Gene Delivery by EGF-Lipoplexes In Vitro and In Vivo

Abstract: These findings indicate that these nanovectors may be an adequate alternative to viral vectors for gene therapy.

Cited by 29 publications

References 28 publications

Liposomal fasudil, a rho-kinase inhibitor, for prolonged pulmonary preferential vasodilation in pulmonary arterial hypertension

Liposomal fasudil, a rho-kinase inhibitor, for prolonged pulmonary preferential vasodilation in pulmonary arterial hypertension

EGFR-targeted poly(ethylene glycol)-distearoylphosphatidylethanolamine micelle loaded with paclitaxel for laryngeal cancer: preparation, characterization andin vitroevaluation

Dicationic Surfactants with Glycine Counter Ions for Oligonucleotide Transportation

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