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 ÂşC). 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 (0.020–0.200 and 0.200–2.00 μmol L^–1), and low quantification limits (2–6 nmol L^–1, 23–69 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 freeze–thaw 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 μmol L^–1 were found

Resveratrol Interaction with Lipid Bilayers: A Synchrotron X‑ray 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 Box–Behnken 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> 230 nm, zeta potential of −34.28 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 25 µg ml⁻¹ in CLZ. Free CLZ solutions exhibited IC₅₀ values of 16 and 20 µg ml⁻¹ 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 poly­(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 (40μM) (red line, 0) alone, incubated in DMPC:SM model membrane at 37 °C. Stern–Volmer plots of the probe DPH in the DMPC:SM model at pH 7.4 and 37 °C with increasing daunorubicin concentration