7 research outputs found
MOESM1 of Brain-targeted delivery of resveratrol using solid lipid nanoparticles functionalized with apolipoprotein E
Additional file 1: Table S1. Characterization of Resveratrol-loaded SLNs: SLN placebo and SLN-Resveratrol (2, 5, 10 and 15 mg of resveratrol). Figure S1. Effect of time of storage on particle size of RSV loaded SLNs with different amounts of RSV. Figure S2. Effect of time of storage on zeta potential of RSV loaded SLNs with different amounts of RSV. Figure S3. Effect of time of storage on entrapment efficiency of RSV loaded SLNs with different amounts ofRSV. Figure S4. In vitro RSV release profiles from RSV loaded SLNs with different amounts of RSV performed in SBF, simulating the blood stream conditions, at body temperature (37 ĂĆC). Figure S5. Images of hCMEC/D3 cells on transwell devices during the 7 days of growing
New Insights on the Biophysical Interaction of Resveratrol with Biomembrane Models: Relevance for Its Biological Effects
Resveratrol
has been widely studied because of its pleiotropic
effects in cancer therapy, neuroprotection, and cardioprotection.
It is believed that the interaction of resveratrol with biological
membranes may play a key role in its therapeutic activity. The capacity
of resveratrol to partition into lipid bilayers, its possible location
within the membrane, and the influence of this compound on the membrane
fluidity were investigated using membrane mimetic systems composed
of egg l-α-phosphatidylcholine (EPC), cholesterol (CHOL),
and sphingomyelin (SM). The results showed that resveratrol has greater
affinity for the EPC bilayers than for EPC:CHOL [4:1] and EPC:CHOL:SM
[1:1:1] membrane models. The increased difficulty in penetrating tight
packed membranes is also demonstrated by fluorescence quenching of
probes and by fluorescence anisotropy measurements. Resveratrol may
be involved in the regulation of cell membrane fluidity, thereby contributing
for cell homeostasis
Development and Validation of a HPLC Method Using a Monolithic Column for Quantification of <i>trans</i>-Resveratrol in Lipid Nanoparticles for Intestinal Permeability Studies
The development of nanodelivery systems
that protect <i>trans</i>-resveratrol is extremely important
to preserve its bioactive properties
in the development of further applications as nutraceuticals to supplement
foods and beverages. In this work, a validated HPLC method was developed
for the quantification of <i>trans</i>-resveratrol in lipid
nanoparticles for application in studies of in vitro intestinal permeability.
The chromatographic separation was achieved in a C18 monolithic column
connected to a fluorometric detector (330/374 nm), by isocratic elution
consisting of 2% acetic acid/acetonitrile (80:20). Two calibration
ranges were established (0.020â0.200 and 0.200â2.00
ÎŒmol L<sup>â1</sup>), and low quantification limits (2â6
nmol L<sup>â1</sup>, 23â69 pg) were achieved. Stability
studies showed that <i>trans</i>-resveratrol is stable for
24 h at 4 °C, and storage at room temperature and freezeâthaw
cycles are not recommended. The proposed method was applied to in
vitro intestinal permeability studies, in which values between 0.05
± 0.01 and 1.8 ± 0.3 ÎŒmol L<sup>â1</sup> were
found
Resveratrol Interaction with Lipid Bilayers: A Synchrotron Xâray Scattering Study
Resveratrol
belongs to the large group of biologically active polyphenol
compounds, with several beneficial health effects including antioxidant
activity, anti-inflammatory action, cardiovascular protection, neuroprotection,
and cancer chemoprevention. In the present study,
the possibility that the effects of resveratrol described above are
caused by resveratrol membrane interactions and structural modifications
of lipid bilayers is evaluated. In this context, it is possible that
resveratrol interacts selectively with lipid domains present in biological
membranes, thereby modulating the localization of the anchored proteins
and controlling their intracellular cascades. This study was conducted
in a synchrotron particle accelerator, where the influence of resveratrol
in the structural organization of lipid domains in bilayers was investigated
using small- and wide-angle X-ray scattering (SAXS and WAXS) techniques.
Membrane mimetic systems composed of egg l-α-phosphatidylcholine
(EPC), cholesterol (CHOL), and sphingomyelin (SM), with different
molar ratios, were used to access the effects of resveratrol on the
order and structure of the membrane. The results revealed that resveratrol
induces phase separation, promoting the formation of lipid domains
in EPC, EPC:CHOL [4:1], and EPC:CHOL:SM [1:1:1] bilayers, which brings
some structural organization to membranes. Therefore, resveratrol
controls lipid packing of bilayers by inducing the organization of
lipid rafts. Moreover, the formation of lipid domains is important
for modulating the activity of many receptors, transmembrane proteins,
and enzymes whose activity depends on the structural organization
of the membrane and on the presence or absence of these organized
domains. This evidence can thereby explain the therapeutic effects
of resveratrol
Supplementary material from Overcoming clofazimine intrinsic toxicity: statistical modelling and characterization of solid lipid nanoparticles
The aim of this work was to develop solid lipid nanoparticles (SLNs) loaded with clofazimine (CLZ) (SLNs-CLZ) to overcome its intrinsic toxicity and low water solubility, for oral drug delivery. A BoxâBehnken design was constructed to unravel the relations between the independent variables in the selected responses. The optimized SLNs-CLZ exhibited the following properties: particle size <i>ca</i> 230â
nm, zeta potential of â34.28â
mV, association efficiency of 72% and drug loading of 2.4%, which are suitable for oral delivery. Further characterization included Fourier transformed infrared spectroscopy that confirmed the presence of the drug and the absence of chemical interactions. By differential scanning calorimetry was verified the amorphous state of CLZ. The storage stability studies ensured the stability of the systems over a period of 12 weeks at 4°C. <i>In vitro</i> cytotoxicity studies evidenced no effect of both drug-loaded and unloaded SLNs on MKN-28 gastric cells and on intestinal cells, namely Caco-2 and HT29-MTX cells up to 25â
”gâ
ml<sup>â1</sup> in CLZ. Free CLZ solutions exhibited IC<sub>50</sub> values of 16 and 20â
”gâ
ml<sup>â1</sup> for Caco-2 and HT29-MTX cells, respectively. It can be concluded that the optimized system, designed considering important variables for the formulation of poorly soluble drugs, represents a promising platform for oral CLZ delivery
Stability Study Perspective of the Effect of Freeze-Drying Using Cryoprotectants on the Structure of Insulin Loaded into PLGA Nanoparticles
This work aimed to evaluate the influence
of a freeze-drying process
using different cryoprotectants on the structure of insulin loaded
into polyÂ(lactic-<i>co</i>-glycolic acid) (PLGA) nanoparticles
and to assess the stability of these nanoparticles upon 6 months of
storage following ICH guidelines. Insulin-loaded PLGA nanoparticles
with a size around 450 nm were dehydrated using a standard freeze-drying
cycle, using trehalose, glucose, sucrose, fructose, and sorbitol at
10% (w/v) as cryoprotectants. All formulations, except those nonadded
of cryoprotectant and added with trehalose, collapsed after freeze-drying.
The addition of cryoprotectants increased the nanoparticles stability
upon storage. FTIR results showed that insulin maintained its structure
after encapsulation in about 88%, decreasing to 71% after freeze-drying.
The addition of cryoprotectants prior to freeze-drying increased insulin
structural stability an average of up to 79%. Formulations collapsed
after freeze-drying showed better protein stabilization upon storage,
in special sorbitol added formulation, preserving 76, 80, and 78%
of insulin structure at 4 °C, 25 °C/60% RH, and 40 °C/75%
RH, respectively. Principal component analysis also showed that the
sorbitol-added formulation showed the most similar insulin structural
modifications among the tested storage conditions. These findings
suggested that regarding nanoparticles stability, cryoprotectants
are versatile to be used in a standard freeze-drying, however they
present different performances on the stabilization of the loaded
protein. Thus, on the freeze-drying of the nanoparticles field, this
work gives rise to the importance of the process of optimization,
searching for a balance between a good obtainable cake with an optimal
structural stabilization of the loaded protein
Kp determination by derivative spectroscopy and Stern Volmer plots of Daunorubicin using a DMPC:SM model system. from A biophysical approach to daunorubicin interaction with model membranes: relevance for the drug's biological activity
Absorption (A) and third-derivative absorption (B) spectra of daunorubicin (40ÎŒM) (red line, 0) alone, incubated in DMPC:SM model membrane at 37 °C. SternâVolmer plots of the probe DPH in the DMPC:SM model at pH 7.4 and 37 °C with increasing daunorubicin concentration