Eduarda Fernandes, Telma B. Soares, Hugo Gonçalves, Marlene Lúcio
Abstract
The goal of this study is to provide tools to minimize trial-and-error in the development of novel lipid-based nanotherapeutics, in favor of a rational design process. For this purpose, we present case-study examples of biophysical assays that help addressing issues of lipid-based nanotherapeutics' profiling and assist in the design of lipid nanocarriers for therapeutic usage. The assays presented are rooted in spectroscopic methods (steady-state and time-resolved fluorescence; UV-Vis derivative spectroscopy; fluorescence anisotropy and fluorescence lifetime image microscopy) and allow accessing physical-chemical interactions between drugs and lipid nanocarriers, as well as studying interactions between lipid-based nanotherapeutics and membranes and/or proteins, as this is a key factor in predicting their therapeutic and off target effects. Derivative spectroscopy revealed Naproxen's high distribution (LogD ≈ 3) in different lipid-based nanocarriers (micelles and unilamellar or multilamellar vesicles) confirming the adequacy of such systems for encapsulating this anti-inflammatory drug. Fluorescence quenching studies revealed that the anti-inflammatory drugs Acemetacin and Indomethacin can reach an inner location at the lipid nanocarrier while being anchored with its carboxylic moiety at the polar headgroup. The least observed quenching effect suggested that Tolmetin is probably located at the polar headgroup region of the lipid nanocarriers and this superficial location may translate in a fast drug release from the nanocarriers. Fluorescent anisotropy measurements indicated that the drugs deeply buried within the lipid nanocarrier where the ones that had a greater fluidizing effect which can also translate in a faster drug release. The drug binding strength to serum albumin was also compared for a free drug (Clonixin) or for the same drug after encapsulation in a lipid nanocarrier DSPC:DODAP (2:1). Under both conditions there is a strong binding to serum albumin, at one binding site, suggesting the need to produce a stealth nanosystem. Finally the cellular uptake of lipid nanocarriers loaded with Daunorubicin was investigated in cancer cells using fluorescence lifetime imaging microscopy. From the images obtained it was possible to conclude that even at short incubation times (15 min) there was a distribution of the drug in the cytoplasm, whereas for longer incubation periods (4 h) the drug has reached the nucleus.
Pharmacology, Toxicology and Pharmaceutical Science
3
11%
Agricultural and Biological Sciences
3
11%
Unspecified
2
7%
Environmental Science
1
4%
Immunology and Microbiology
1
4%
Other
3
11%
Unknown
14
52%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 July 2020.
All research outputs
#15,207,446
of 24,143,470 outputs
Outputs from Frontiers in Chemistry
#1,122
of 6,356 outputs
Outputs of similar age
#189,233
of 333,512 outputs
Outputs of similar age from Frontiers in Chemistry
#56
of 190 outputs
Altmetric has tracked 24,143,470 research outputs across all sources so far. This one is in the 34th percentile – i.e., 34% of other outputs scored the same or lower than it.
So far Altmetric has tracked 6,356 research outputs from this source. They receive a mean Attention Score of 2.2. This one has done well, scoring higher than 80% of its peers.
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We're also able to compare this research output to 190 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 68% of its contemporaries.
