In vivo imaging of DNA lipid nanocapsules after systemic administration in a melanoma mouse model

David, Stéphanie; Carmoy, Nathalie; Resnier, Pauline; Denis, Caroline; Miséry, Laurent; Pitard, Bruno; Benoit, Jean‐Pierre; Passirani, Catherine; Montier, Tristan

doi:10.1016/j.ijpharm.2011.06.031

Cited by 25 publications

(21 citation statements)

References 37 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This result can be explained by the benefit of the nanocapsule shell that hides the positive charges of the lipids thanks to weak links with negative PEG dipoles (Vonarbourg et al, 2005), thereby conferring stealth property to our LNCs in opposition to lipoplexes. This great enhancement in the behavior of our LNCs is more likely due to the presence of PEG chains at the surface of LNCs, as demonstrated in our previous works on DNA LNCs (David et al, 2012a). To evaluate this, in vivo experiments should be realized to define the half-life time and biodistribution of siRNA LNCs in a murine glioma model.…”

Section: Discussionmentioning

confidence: 82%

EGFR siRNA lipid nanocapsules efficiently transfect glioma cells in vitro

Resnier

David

Lautram

et al. 2013

International Journal of Pharmaceutics

Self Cite

View full text Add to dashboard Cite

Glioma are the most common malignant tumors of the central nervous system and remain associated with poor prognosis, despite the combination of chemotherapy and radiotherapy. EGFR targeting represents an interesting strategy to treat glioma. Indeed, a high level of endothelial growth factor receptors expression (EGFR), involved in the malignancy of the tumor, has been observed in glioma. Our strategy consisted in using EGFR siRNA entrapped into lipid nanocapsules (LNCs) via cationic liposomes. In vitro analyses on U87MG human glioma cells were performed to evaluate firstly the capacity of LNCs to efficiently deliver the siRNA and secondly the effect of EGFR siRNA targeting on U87MG proliferation. Then, the complement protein consumption was evaluated by CH50 assays to verify the suitability of the siRNA LNCs for systemic administration. The EGFR siRNA LNCs exhibited an adequate size lower than 150 nm as well as a neutral surface charge. The IC50 profile together with the 63% of protein extinction demonstrated the significant action of EGFR siRNA LNCs compared to scrambled LNCs. Dose and time-dependent survival assays showed a decrease of U87MG growth evaluated at 38%. Finally, low complement consumption demonstrated the suitability of EGFR siRNA LNCs for intravenous injection. In conclusion, EGFR siRNA LNCs demonstrated their capacity to efficiently encapsulate and deliver siRNA into U87MG human glioma cells, and will therefore be usable in the future for in vivo evaluation.

show abstract

Section: Discussionmentioning

confidence: 82%

EGFR siRNA lipid nanocapsules efficiently transfect glioma cells in vitro

Resnier

David

Lautram

et al. 2013

International Journal of Pharmaceutics

Self Cite

View full text Add to dashboard Cite

show abstract

“…Therefore, PEG-NC prepared at pH 9 showed a controlled release profile, in contrast with the uncontrolled behavior of PEG-NC prepared at pH 7. Sustained release profiles have been also observed from some lipid nanocarriers upon deprotonation of doxorubicin [40] and etoposide [27].…”

Section: In Vitro Drug Releasementioning

confidence: 85%

“…We also incorporated a protective PEG coating around the nanostructure by including PEG-STE as an additional component. The use of PEG-linked lipids has been previously described as an effective strategy to PEGylate lipid systems that avoids chemical conjugation and the use of costly PEGylated phospholipids [26][27][28]. PEG-NC were prepared following a solvent displacement technique, a simple and mild method that is easily scalable.…”

Section: Preparation and Characterization Of Peg-ncmentioning

confidence: 99%

“…For instance, the group of Benoit et al observed a significant enhancement of the therapeutic effect of several drugs formulated in PEG-NC such as etoposide [27], tamoxifen [28], or paclitaxel [29].…”

Section: In Vitro Antitumor Efficacy Studiesmentioning

confidence: 99%

“…Having discarded a direct toxic effect of PEG-NC, the higher efficacy of the drugs upon encapsulation in PEG-NC can be attributed to two effects: (a) the easier internalization of the loaded PEG-NC into the cytosol as compared to the drug alone [27][28], or/and (b) the possible inhibition of the efflux mechanisms of the cancer cells due to the presence of PEG polymers or by the nanocapsules themselves [41][42]. In fact, it has been widely reported that poloxamer inhibits many cell's efflux pumps, such as P-gP or MDR proteins, through different pathways [43].…”

Section: In Vitro Antitumor Efficacy Studiesmentioning

confidence: 99%

See 2 more Smart Citations

PEGylated Lipid Nanocapsules with Improved Drug Encapsulation and Controlled Release Properties

Hervella¹,

Alonso-Sande²,

Lédo³

et al. 2014

CTMC

View full text Add to dashboard Cite

Drugs with poor lipid and water solubility are some of the most challenging to formulate in nanocarriers, typically resulting in low encapsulation efficiencies and uncontrolled release profiles. PEGylated nanocapsules (PEG-NC) are known for their amenability to diverse modifications that allow the formation of domains with different physicochemical properties, an interesting feature to address a drug encapsulation problem. We explored this problem by encapsulating in PEG-NC the promising anticancer drug candidate F10320GD1, used herein as a model for compounds with such characteristics. The nanocarriers were prepared from Miglyol®, lecithin and PEG-sterate through a solvent displacement technique. The resulting system was a homogeneous suspension of particles with size around 200 nm. F10320GD1 encapsulation was found to be very poor (<15%) if PEG-NC were prepared using water as continuous phase; but we were able to improve this value to 85% by fixing the pH of the continuous phase to 9. Interestingly, this modification also improved the controlled release properties and the chemical stability of the formulation during storage. These differences in pharmaceutical properties together with physicochemical data suggest that the pH of the continuous phase used for PEG-NC preparation can modify drug allocation, from the external shell towards the inner lipid core of the nanocapsules. Finally, we tested the bioactivity of the drug-loaded PEG-NC in several tumor cell lines, and also in endothelial cells. The results indicated that drug encapsulation led to an improvement on drug cytotoxicity in tumor cells, but not in non-tumor endothelial cells. Altogether, the data confirms that PEG-NC show adequate delivery properties for F10320GD1, and underlines its possible utility as an anticancer therapy. Graphical Abstract:!

show abstract

Efficient in vitro gene therapy with PEG siRNA lipid nanocapsules for passive targeting strategy in melanoma

Resnier

LeQuinio

Lautram

et al. 2014

Biotechnology Journal

Self Cite

View full text Add to dashboard Cite

Small interfering RNA (siRNA)-mediated gene therapy is a promising strategy to temporarily inhibit the expression of proteins implicated in carcinogenesis or chemotherapy resistance. Although intra-tumoral administration can be envisaged, studies currently focus on formulating nanomedicines for intravenous injection to target tumor sites as well as metastases. The development of synthetic nanoparticles and liposomes has advanced greatly during the last decade. The objective of this work consists in formulating and optimizing the encapsulation of siRNA into lipid nanocapsules (LNCs) for efficient gene therapy to target melanoma cells. SiRNA LNCs were prepared from DOTAP/DOPE lipoplexes, and the siRNA amount and lipid/siRNA charge ratio were assayed to improve the stability and the encapsulation yield. Cryo-TEM imaging of the siRNA lipoplexes and LNC morphology revealed specific organization of the siRNA DOTAP/DOPE lipoplexes as well as specific lipid microstructures that can be eliminated by purification. No cytotoxicity of the siRNA LNCs against the melanoma SK-Mel28 cell line was observed at concentrations of up to 500 ng/mL siRNA. In vitro siRNA transfection experiments, compared to Oligofectamine™, demonstrated interesting targeted gene silencing effects. Finally, complement activation assays confirmed the feasibility of the PEGylation of siRNA LNCs as part of a passive targeting strategy for future in vivo melanoma- and metastasis-targeting experiments.

show abstract

In vivo imaging of DNA lipid nanocapsules after systemic administration in a melanoma mouse model

Cited by 25 publications

References 37 publications

EGFR siRNA lipid nanocapsules efficiently transfect glioma cells in vitro

EGFR siRNA lipid nanocapsules efficiently transfect glioma cells in vitro

PEGylated Lipid Nanocapsules with Improved Drug Encapsulation and Controlled Release Properties

Efficient in vitro gene therapy with PEG siRNA lipid nanocapsules for passive targeting strategy in melanoma

Contact Info

Product

Resources

About