Conventional versus stealth lipid nanoparticles: Formulation and in vivo fate prediction through FRET monitoring

Lainé, Anne-Laure; Gravier, Julien; Henry, Maxime; Sancey, Lucie; Bejaud, Jérôme; Pancani, Elisabetta; Wiber, Margaux; Texier, Isabelle; Coll, Jean‐Luc; Benoit, Jean‐Pierre; Passirani, Catherine

doi:10.1016/j.jconrel.2014.05.042

Cited by 85 publications

(67 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, TwN (polysorbate 20), a polyoxyethylene derivative, was used as a hydrophilic surfactant. The hydrophilic polyoxyethylene polymer, along with the hydrophobic LcN, confers a highly protective amphiphilic stealth outer cover to the SLN, which provides longcirculating properties to the carrier system by evading clearance by the reticuloendothelial system (25,26). The longcirculating carriers act as circulating drug reservoirs in blood and aid passive targeting.…”

Section: Preparation Of Imt-slnmentioning

confidence: 99%

Effects of Formulation Variables on the Particle Size and Drug Encapsulation of Imatinib-Loaded Solid Lipid Nanoparticles

et al. 2015

View full text Add to dashboard Cite

Abstract. Imatinib (IMT), an anticancer agent, inhibits receptor tyrosine kinases and is characterized by poor aqueous solubility, extensive first-pass metabolism, and rapid clearance. The aims of the current study are to prepare imatinib-loaded solid lipid nanoparticles (IMT-SLN) and study the effects of associated formulation variables on particle size and drug encapsulation on IMT-SLN using an experimental design. IMT-SLN was optimized by use of a Bcombo^approach involving Plackett-Burman design (PBD) and Box-Behnken design (BBD). PBD screening resulted in the determination of organic-toaqueous phase ratio (O/A), drug-to-lipid ratio (D/L), and amount of Tween® 20 (Tw20) as three significant variables for particle size (S z ), drug loading (DL), and encapsulation efficiency (EE) of IMT-SLN, which were used for optimization by BBD, yielding an optimized criteria of O/A=0.04, D/L=0.03, and Tw20=2.50%w/v. The optimized IMT-SLN exhibited monodispersed particles with a size range of 69.0±0.9 nm, ζ-potential of −24.2±1.2 mV, and DL and EE of 2.9±0.1 and 97.6±0.1%w/w, respectively. Results of in vitro release study showed a sustained release pattern, presumably by diffusion and erosion, with a higher release rate at pH 5.0, compared to pH 7.4. In conclusion, use of the combo experimental design approach enabled clear understanding of the effects of various formulation variables on IMT-SLN and aided in the preparation of a system which exhibited desirable physicochemical and release characteristics.

show abstract

Section: Preparation Of Imt-slnmentioning

confidence: 99%

Effects of Formulation Variables on the Particle Size and Drug Encapsulation of Imatinib-Loaded Solid Lipid Nanoparticles

et al. 2015

View full text Add to dashboard Cite

show abstract

“…8 Due to the spatial sensitivity of the process, FRET has been used to study molecular interactions such as protein−protein interactions 9,10 and lipid dynamics. 11,12 It has also been used as a mechanism for the activation of photosensitizing molecular beacons, 6,13 integrated into nanoplatforms to create long Stokes shift fluorescent probes, 14 and used in the study of nanoparticle stability in polymer micelles, 15,16 lipid nanoparticles, 17 lipidcoated quantum dot micelles, 18 and biomimetic lipoproteins. 19 Herein, we evaluate the feasibility of integrating a structural sensing functionality into porphysomes through the application of FRET (FRETysomes) (Figure 1).…”

Section: ■ Introductionmentioning

confidence: 99%

Self-Sensing Porphysomes for Fluorescence-Guided Photothermal Therapy

Takada²,

Jin³

et al. 2015

Bioconjugate Chem.

View full text Add to dashboard Cite

Porphysomes are highly quenched unilamellar porphyrin-lipid nanovesicles with structurally dependent photothermal properties. The high packing density of porphyrin molecules in the lipid bilayer enables their application in photothermal therapy, whereas the partial disruption of the porphysome structure over time restores the porphyrin fluorescence and enables the fluorescence-guided photothermal ablation. This conversion is a time-dependent process and cannot be easily followed using existing analytical techniques. Here we present the design of a novel self-sensing porphysome (FRETysomes) capable of fluorescently broadcasting its structural state through Förster resonance energy transfer. By doping in a near-infrared emitting fluorophore, it is possible to divert a small fraction of the absorbed energy toward fluorescence emission which provides information on whether the vesicle is intact or disrupted. Addition of bacteriopheophorbide-lipid into the vesicle bilayer as a fluorescence acceptor (0.5-7.5 mol %) yields a large separation of 100 nm between the absorption and fluorescence bands of the nanoparticle. Furthermore, a progressive increase in FRET efficiency (14.6-72.7%) is observed. Photothermal heating and serum stability in FRETysomes is comparable with the undoped porphysomes. The fluorescence arising from the energy transfer between the donor and acceptor dyes can be clearly visualized in vivo through hyperspectral imaging. By calculating the ratio between the acceptor and donor fluorescence, it is possible to determine the structural fate of the nanovesicles. We observe using this technique that tumor accumulation of structurally intact porphyrin-lipid nanovesicles persists at 24 and 48 h postinjection. The development of FRETysomes offers a unique and critical imaging tool for planning porphysome-enabled fluorescence-guided photothermal treatment, which maximizes light-induced thermal toxicity.

show abstract

“…Imparting the stealth properties to the nanocarriers has been well established to bypass hepatic Kupffer cells upon intravenous administration. Hydrophilic surfaces of the stealth nanoparticles avoid opsonization and then phagocytosis, which result in lower concentration of the stealth nanoparticles in the liver Kupffer cells and subsequently enhance splenic delivery [15,16]. Alterations of other physicochemical properties like particle size [17,18], shape [19], and charge [20] have also been reported to bypass hepatic Kupffer cells.…”

Section: Introductionmentioning

confidence: 99%

Nanocarriers for spleen targeting: anatomo-physiological considerations, formulation strategies and therapeutic potential

Jindal

2016

Drug Deliv. and Transl. Res.

View full text Add to dashboard Cite

There are several clinical advantages of spleen targeting of nanocarriers. For example, enhanced splenic concentration of active agents could provide therapeutic benefits in spleen resident infections and hematological disorders including malaria, hairy cell leukemia, idiopathic thrombocytopenic purpura, and autoimmune hemolytic anemia. Furthermore, spleen delivery of immunosuppressant agents using splenotropic carriers may reduce the chances of allograft rejection in organ transplantation. Enhanced concentration of radiopharmaceuticals in the spleen may improve visualization of the organ, which could provide benefit in the diagnosis of splenic disorders. Unique anatomical features of the spleen including specialized microvasculature environment and slow blood circulation rate enable it an ideal drug delivery site. Because there is a difference in blood flow between spleen and liver, splenic delivery is inversely proportional to the hepatic uptake. It is therefore desirable engineering of nanocarriers, which, upon intravenous administration, can avoid uptake by hepatic Kupffer cells to enhance splenic localization. Stealth and non-spherical nanocarriers have shown enhanced splenic delivery of active agents by avoiding hepatic uptake. The present review details the research in the field of splenotropy. Formulation strategies to design splenotropic drug delivery systems are discussed. The review also highlights the clinical relevance of spleen targeting of nanocarriers and application in diagnostics.

show abstract

Conventional versus stealth lipid nanoparticles: Formulation and in vivo fate prediction through FRET monitoring

Cited by 85 publications

References 42 publications

Effects of Formulation Variables on the Particle Size and Drug Encapsulation of Imatinib-Loaded Solid Lipid Nanoparticles

Effects of Formulation Variables on the Particle Size and Drug Encapsulation of Imatinib-Loaded Solid Lipid Nanoparticles

Self-Sensing Porphysomes for Fluorescence-Guided Photothermal Therapy

Nanocarriers for spleen targeting: anatomo-physiological considerations, formulation strategies and therapeutic potential

Contact Info

Product

Resources

About