The effects of membrane composition (phospholipid type and amount of cholesterol), liposome size, drug/lipid ratio (loading) and nature of the amphiphilic gadolinium (Gd) chelate on the incorporation efficacy and magnetic resonance (MR) contrast efficacy (longitudinal (T1) relaxivity) were investigated using a fractional factorial design. A highly lipophilic Gd-chelate was required to ensure complete liposome incorporation. High T1-relaxivity was obtained by using liposomes composed of cholesterol and phospholipids with short acyl chain lengths (dimyristoyl phosphatidyl choline (DMPC) and dimyristoyl phosphatidyl glycerol (DMPG). Two key factors, the loading of Gd-chelate and the amount of cholesterol in small-sized DMPC/DMPG liposomes, were studied further in a central composite optimising design. A robust high relaxivity region was identified, comprising high loading of cholesterol and Gd-chelate. However, the highest T1-relaxivity (52 mM(-1) s(-1)) was found in an area containing no cholesterol and low content of Gd-chelate. Nuclear magnetic resonance dispersion (NMRD) profiles were obtained for five of the liposome compositions from the optimising design, and high relaxivity peaks in the 20 MHz region confirmed the presence of Gd-chelates with a long tau(R). A liposome formulation was selected for surface modification with polyethylene glycol (PEG), without having any effect on the T1-relaxivity.

Download full-text PDF

Source
http://dx.doi.org/10.1016/s0378-5173(01)00935-8DOI Listing

Publication Analysis

Top Keywords

amphiphilic gadolinium
8
membrane composition
8
incorporation efficacy
8
amount cholesterol
8
magnetic resonance
8
dimyristoyl phosphatidyl
8
optimising design
8
high relaxivity
8
cholesterol
5
liposomes carriers
4

Similar Publications

Amphiphilic self-assembling peptides: formulation and elucidation of functional nanostructures for imaging and smart drug delivery.

Anal Bioanal Chem

December 2024

Institute of Chemistry for Life & Health Sciences (iCLeHS), Chimie ParisTech, PSL University, CNRS 8060, 75005, Paris, France.

The rational design of self-assembled peptide-based nanostructures for theranostics applications requires in-depth physicochemical characterization of the peptide nanostructures, to understand the mechanism and the interactions involved in the self-assembly, allowing a better control of the objects' physicochemical and functional properties for theranostic applications. In this work, several complementary characterization methods, such as dynamic light scattering, transmission electron microscopy, circular dichroism, Taylor dispersion analysis, and capillary electrophoresis, were used to study and optimize the self-assembly of pH-sensitive short synthetic amphiphilic peptides containing an RGD motif for active targeting of tumor cells and smart drug delivery. The combined methods evidenced the spontaneous formation of nanorods (L = 50 nm, d = 10 nm) at pH 11, stabilized by β-sheets.

View Article and Find Full Text PDF

Self-assembled lipid nanoparticles containing Gd-chelating lipids are a new type of positive magnetic resonance imaging contrast agents (MRI CAs). High molecular weight imposes reduced molecular reorientation () and corresponding longer reorientation correlation times (), finally resulting in overall high relaxivity () of such contrast agents. Therefore, we report nanoassemblies based on two types of amphiphile molecules: glyceryl monooleate (GMO) as a matrix embedded with DTPA-bis(stearylamide) and its gadolinium salt (DTPA-BSA-Gd) as a Gd-chelating lipid, stabilized by surfactant Pluronic F127 molecules.

View Article and Find Full Text PDF
Article Synopsis
  • - The text discusses the search for safer MRI contrast agents due to concerns over nephrogenic systemic fibrosis (NSF) linked to gadolinium ions in patients with kidney problems, leading to interest in manganese (Mn)-based alternatives.
  • - A new Mn(II) complex, created with a pentadentate ligand (Li[BenzPic]), shows strong stability and behaves similarly to gadolinium-based agents, specifically exhibiting good relaxivity in MRI scans.
  • - In studies with healthy mice, this new complex demonstrated excellent MRI signal enhancement, particularly in the liver and gallbladder, indicating its potential effectiveness as a contrast agent.
View Article and Find Full Text PDF

Protease-Mediated Contrast Enhancement of Multilayered Magneto-Gadolinium Nanostructures for Imaging and Magnetic Hyperthermia.

ACS Appl Mater Interfaces

February 2024

Nanomaterials for Biomedical Applications, Istituto Italiano di Tecnologia, 16163 Genova, Italy.

In this work, we constructed a multifunctional composite nanostructure for combined magnetic hyperthermia therapy and magnetic resonance imaging based on and signals. First, iron oxide nanocubes with a benchmark heating efficiency for magnetic hyperthermia were assembled within an amphiphilic polymer to form magnetic nanobeads. Next, poly(acrylic acid)-coated inorganic sodium gadolinium fluoride nanoparticles were electrostatically loaded onto the magnetic nanobead surface via a layer-by-layer approach by employing a positively charged enzymatic-cleavable biopolymer.

View Article and Find Full Text PDF

MRI contrast agents with high kinetic stability and relaxivity are the key objectives in the field. We previously reported that Gd-DOTA backboned-bound branched polymers possess high kinetic stability and significantly increased relaxivity than traditional branched polymer contrast agents. In this work, non-PEGylated and PEGylated amphiphilic Gd-DOTA backboned-bound branched polymers [P(GdDOTA-C), P(GdDOTA-C), mPEG-P(GdDOTA-C), and mPEG-P(GdDOTA-C)] were obtained by sequential introduction of rigid carbon chains (1,6-hexamethylenediamine or 1,10-diaminodecane) and mPEG into the structure of Gd-DOTA backboned-bound branched polymers.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!