Optimization of a Solid-Phase Extraction Procedure for the Analysis of Drug-Loaded Lipid Nanoparticles and its Application to the Determination of Leakage and Release Profiles.

To understand and predict the efficacy and toxicity of nanoparticle-based drugs in vivo, the free and entrapped forms of the drug have to be determined using suitable characterization methods. Herein, a solid-phase extraction (SPE) method combined with high-performance liquid chromatography (HPLC) measurements were used to separately quantify free and entrapped cyclosporine A (CsA) in 50 and 120 nm-sized lipid nanoparticles (NPs). Combined with colloidal stability measurements, HPLC quantification of the free and entrapped drug, separated using SPE, was used to monitor the stability of the nanotherapeutics under storage or physiological conditions.

Nanostructured lipid carriers accumulate in atherosclerotic plaques of ApoE mice.

Nanostructured lipid carriers (NLC) might represent an interesting approach for the identification and targeting of rupture-prone atherosclerotic plaques. In this study, we evaluated the biodistribution, targeting ability and safety of Cu-fonctionalized NLC in atherosclerotic mice. Cu-chelating-NLC (51.

Quantification of Surface GalNAc Ligands Decorating Nanostructured Lipid Carriers by UPLC-ELSD.

Nanoparticles have been extensively studied for drug delivery and targeting to specific organs. The functionalization of the nanoparticle surface by site-specific ligands (antibodies, peptides, saccharides) can ensure efficient recognition and binding with relevant biological targets. One of the main challenges in the development of these decorated nanocarriers is the accurate quantification of the amount of ligands on the nanoparticle surface.

Development and validation of a novel UPLC-ELSD method for the assessment of lipid composition of nanomedicine formulation.

Lipid nanocarriers incorporating glycerides, polyethylene glycol (PEG)-stearates and phospholipids have attracted great attention for in vivo diagnostic, in vivo imaging, activated or non-activated targeted drug delivery. For quality control purposes, the development of appropriate methods for the quantification of their lipid components is needed. In the present study, we developed an analytical method for lipid quantification in formulated nanoparticles.

Measuring Particle Size Distribution by Asymmetric Flow Field Flow Fractionation: A Powerful Method for the Preclinical Characterization of Lipid-Based Nanoparticles.

Particle size distribution and stability are key attributes for the evaluation of the safety and efficacy profile of medical nanoparticles (Med-NPs). Measuring particle average size and particle size distribution is a challenging task which requires the combination of orthogonal high-resolution sizing techniques, especially in complex biological media. Unfortunately, despite its limitations, due to its accessibility, low cost, and easy handling, batch mode dynamic light scattering (DLS) is still very often used as the only approach to measure particle size distribution in the nanomedicine field.

Electrospinning in water and in situ crosslinking of hyaluronic acid / cyclodextrin nanofibers: Towards wound dressing with controlled drug release.

Hyaluronic acid (HA) is widely investigated due to its high potential for wound dressing applications. The fabrication of biomimetic HA-based scaffolds by electrospinning is thus extensively studied. However, HA is often dissolved in toxic organic solvents to allow the efficient production of electrospun nanofibers.

Development and validation of an HPLC-fluorescence method for the quantification of IR780-oleyl dye in lipid nanoparticles.

A reversed-phase (RP) high-performance liquid chromatography (HPLC) method for the content determination of IR780-oleyl (IRO) dye in lipid nanoparticles was developed and validated. Chromatographic separation was performed on a RP C18 column with a gradient program of water and acetonitrile both with 0.1% (v/v) TFA, at a flow rate of 1.

Lipid nanoemulsions and liposomes improve photodynamic treatment efficacy and tolerance in CAL-33 tumor bearing nude mice.

Background: Photodynamic therapy (PDT) as promising alternative to conventional cancer treatments works by irradiation of a photosensitizer (PS) with light, which creates reactive oxygen species and singlet oxygen (O), that damage the tumor. However, a routine use is hindered by the PS's poor water solubility and extended cutaneous photosensitivity of patients after treatment. In our study we sought to overcome these limitations by encapsulation of the PS m-tetrahydroxyphenylchlorin (mTHPC) into a biocompatible nanoemulsion (Lipidots).

Photoinduced effects of m-tetrahydroxyphenylchlorin loaded lipid nanoemulsions on multicellular tumor spheroids.

Background: Photosensitizers are used in photodynamic therapy (PDT) to destruct tumor cells, however, their limited solubility and specificity hampers routine use, which may be overcome by encapsulation. Several promising novel nanoparticulate drug carriers including liposomes, polymeric nanoparticles, metallic nanoparticles and lipid nanocomposites have been developed. However, many of them contain components that would not meet safety standards of regulatory bodies and due to difficulties of the manufacturing processes, reproducibility and scale up procedures these drugs may eventually not reach the clinics.

Solid Phase Extraction as an Innovative Separation Method for Measuring Free and Entrapped Drug in Lipid Nanoparticles.

Purpose: Contrary to physical characterization techniques for nanopharmaceuticals (shape, size and zeta-potential), the techniques to quantify the free and the entrapped drug remain very few and difficult to transpose in routine analytical laboratories. The application of Solid Phase Extraction (SPE) technique was investigated to overcome this challenge.

Methods: The separation of free and entrapped drug by SPE was quantitatively validated by High Performance Liquid Chromatography.

Preparation and characterization of mTHPC-loaded solid lipid nanoparticles for photodynamic therapy.

Among various attempts to enhance the therapeutic efficacy of photodynamic therapy (PDT), the specific delivery of photosensitizer (PS) in the tumor tissue is expected to improve its clinical applications. The aim of this study was to engineer lipid nanoparticles (LNP) with different sizes and various PS contents, using simple solvent-free and easily scale up manufacturing processes. Meso-(tetrahydroxyphenyl) chlorin (mTHPC) is one of the most potent photoactive compounds for clinical use.

Lipidots: competitive organic alternative to quantum dots for in vivo fluorescence imaging.

The use of fluorescent nanostructures can bring several benefits on the signal to background ratio for in vitro microscopy, in vivo small animal imaging, and image-guided surgery. Fluorescent quantum dots (QDs) display outstanding optical properties, with high brightness and low photobleaching rate. However, because of their toxic element core composition and their potential long term retention in reticulo-endothelial organs such as liver, their in vivo human applications seem compromised.

Preparation and characterization of highly stable lipid nanoparticles with amorphous core of tuneable viscosity.

Lipid nanoparticles (LNP) have been designed based on low cost and human-use approved excipients, and manufactured by an easy, robust, and up-scalable process. Fluid colloidal dispersions or gel viscous formulations of highly stable nanoparticles (more than 12 month stability is achieved for some formulations) can be obtained. Their physicochemical properties are studied by Dynamic Light Scattering, Differential Scanning Calorimetry, and NMR.

How to prepare and stabilize very small nanoemulsions.

Practical and theoretical considerations that apply when aiming to formulate by ultrasonication very small nanoemulsions (particle diameter up to 150 nm) with very high stability are presented and discussed. The droplet size evolution during sonication can be described by a monoexponential function of the sonication time, the characteristic time scale depending essentially on the applied power. A unique master curve is obtained when plotting the mean diameter size evolution as a function of sonication energy.