A small TAT-TrkB peptide prevents BDNF receptor cleavage and restores synaptic physiology in Alzheimer's disease.

In Alzheimer's disease (AD), amyloid ß (Aß)-triggered cleavage of TrkB-FL impairs brain-derived neurotrophic factor (BDNF) signaling, thereby compromising neuronal survival, differentiation, and synaptic transmission and plasticity. Using cerebrospinal fluid and postmortem human brain samples, we show that TrkB-FL cleavage occurs from the early stages of the disease and increases as a function of pathology severity. To explore the therapeutic potential of this disease mechanism, we designed small TAT-fused peptides and screened their ability to prevent TrkB-FL receptor cleavage. Among these, a TAT-TrkB peptide with a lysine-lysine linker prevented TrkB-FL cleavage both in vitro and in vivo and rescued synaptic deficits induced by oligomeric Aß in hippocampal slices. Furthermore, this TAT-TrkB peptide improved the cognitive performance, ameliorated synaptic plasticity deficits and prevented Tau pathology progression in vivo in the 5XFAD mouse model of AD. No evidence of liver or kidney toxicity was found. We provide proof-of-concept evidence for the efficacy and safety of this therapeutic strategy and anticipate that this TAT-TrkB peptide has the potential to be a disease-modifying drug that can prevent and/or reverse cognitive deficits in patients with AD.

The Role of Amyloid ß-Biomembrane Interactions in the Pathogenesis of Alzheimer's Disease: Insights from Liposomes as Membrane Models.

The aggregation and deposition of amyloid ß (Aß) peptide onto neuronal cells, with consequent cellular membrane perturbation, are central to the pathogenesis of Alzheimer's disease (AD). Substantial evidence reveals that biological membranes play a key role in this process. Thus, elucidating the mechanisms by which Aß interacts with biomembranes and becomes neurotoxic is fundamental to developing effective therapies for this devastating progressive disease. However, the structural basis behind such interactions is not fully understood, largely due to the complexity of natural membranes. In this context, lipid biomembrane models provide a simplified way to mimic the characteristics and composition of membranes. Aß-biomembrane interactions have been extensively investigated applying artificial membrane models to elucidate the molecular mechanisms underlying the AD pathogenesis. This review summarizes the latest findings on this field using liposomes as biomembrane model, as they are considered the most promising 3D model. The current challenges and future directions are discussed.

(De)stabilization of Alpha-Synuclein Fibrillary Aggregation by Charged and Uncharged Surfactants.

Parkinson's disease (PD) is the second most common neurodegenerative disorder. An important hallmark of PD involves the pathological aggregation of proteins in structures known as Lewy bodies. The major component of these proteinaceous inclusions is alpha (α)-synuclein. In different conditions, α-synuclein can assume conformations rich in either α-helix or ß-sheets. The mechanisms of α-synuclein misfolding, aggregation, and fibrillation remain unknown, but it is thought that ß-sheet conformation of α-synuclein is responsible for its associated toxic mechanisms. To gain fundamental insights into the process of α-synuclein misfolding and aggregation, the secondary structure of this protein in the presence of charged and non-charged surfactant solutions was characterized. The selected surfactants were (anionic) sodium dodecyl sulphate (SDS), (cationic) cetyltrimethylammonium chloride (CTAC), and (uncharged) octyl ß-D-glucopyranoside (OG). The effect of surfactants in α-synuclein misfolding was assessed by ultra-structural analyses, in vitro aggregation assays, and secondary structure analyses. The α-synuclein aggregation in the presence of negatively charged SDS suggests that SDS-monomer complexes stimulate the aggregation process. A reduction in the electrostatic repulsion between N- and C-terminal and in the hydrophobic interactions between the NAC (non-amyloid beta component) region and the C-terminal seems to be important to undergo aggregation. Fourier transform infrared spectroscopy (FTIR) measurements show that ß-sheet structures comprise the assembly of the fibrils.

Fluorinated Molecules and Nanotechnology: Future 'Avengers' against the Alzheimer's Disease?

Alzheimer's disease (AD) is a serious health concern, affecting millions of people globally, which leads to cognitive impairment, dementia, and inevitable death. There is still no medically accepted treatment for AD. Developing therapeutic treatments for AD is an overwhelming challenge in the medicinal field, as the exact mechanics underlying its devastating symptoms is still not completely understood. Rather than the unknown mechanism of the disease, one of the limiting factors in developing new drugs for AD is the blood-brain barrier (BBB). A combination of nanotechnology with fluorinated molecules is proposed as a promising therapeutic treatment to meet the desired pharmacokinetic/physiochemical properties for crossing the BBB passage. This paper reviews the research conducted on fluorine-containing compounds and fluorinated nanoparticles (NPs) that have been designed and tested for the inhibition of amyloid-beta (Aß) peptide aggregation. Additionally, this study summarizes fluorinated molecules and NPs as promising agents and further future work is encouraged to be effective for the treatment of AD.

Resveratrol and Grape Extract-loaded Solid Lipid Nanoparticles for the Treatment of Alzheimer's Disease.

The aggregation of amyloid-ß peptide (Aß) has been linked to the formation of neuritic plaques, which are pathological hallmarks of Alzheimer's disease (AD). Various natural compounds have been suggested as therapeutics for AD. Among these compounds, resveratrol has aroused great interest due to its neuroprotective characteristics. Here, we provide evidence that grape skin and grape seed extracts increase the inhibition effect on Aß aggregation. However, after intravenous injection, resveratrol is rapidly metabolized into both glucuronic acid and sulfate conjugations of the phenolic groups in the liver and intestinal epithelial cells (within less than 2 h), which are then eliminated. In the present study, we show that solid lipid nanoparticles (SLNs) functionalized with an antibody, the anti-transferrin receptor monoclonal antibody (OX26 mAb), can work as a possible carrier to transport the extract to target the brain. Experiments on human brain-like endothelial cells show that the cellular uptake of the OX26 SLNs is substantially more efficient than that of normal SLNs and SLNs functionalized with an unspecific antibody. As a consequence, the transcytosis ability of these different SLNs is higher when functionalized with OX-26.

Folic-Acid-Conjugated Poly (Lactic-Co-Glycolic Acid) Nanoparticles Loaded with Gallic Acid Induce Glioblastoma Cell Death by Reactive-Oxygen-Species-Induced Stress.

Glioblastoma (GBM) conventional treatment is not curative, and it is associated with severe toxicity. Thus, natural compounds with anti-cancer properties and lower systemic toxicity, such as gallic acid (GA), have been explored as alternatives. However, GA's therapeutic effects are limited due to its rapid metabolism, low bioavailability, and low permeability across the blood-brain barrier (BBB). This work aimed to develop poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) modified with folic acid (FA), as its receptor is overexpressed in BBB and GBM cells, for GA delivery to enhance its therapeutic efficacy. The preparation of NPs was optimized by a central composite design (CCD). The obtained NPs showed physicochemical features suitable for drug internalization in BBB and tumor cells (sizes below 200 nm, monodispersity, and negative surface charge) and the ability to maintain a slow and sustained release for 40 days. In vitro studies using a human GBM cell line (U215) revealed the NPs' ability to accumulate in the target cells, further promoting GA antiproliferative activity by inducing the production of intracellular reactive oxygen species (ROS). Furthermore, GA encapsulation in the developed nanosystems conferred higher protection to healthy cells.

Chitosan-PLGA mucoadhesive nanoparticles for gemcitabine repurposing for glioblastoma therapy.

Glioblastoma (GBM) is a highly deadly brain tumor that does not respond satisfactorily to conventional treatment. The non-alkylating agent gemcitabine (GEM) has been proposed for treating GBM. It can overcome MGMT protein-mediated resistance, a major limitation of conventional therapy with the alkylating agent temozolomide (TMZ). However, GEM's high systemic toxicity and poor permeability across the blood-brain barrier (BBB) pose significant challenges for its delivery to the brain. Thus, mucoadhesive poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) coated with chitosan (CH), suitable for intranasal GEM delivery, were proposed in this work. A central composite design (CCD) was implemented for NPs optimization, and NPs with appropriate characteristics for intranasal administration were obtained. in vitro studies revealed that the NPs possess excellent mucoadhesive properties and the ability to selectively release GEM in the simulated tumor tissue environment. in vitro studies using two human GBM cell lines (U215 and T98G) revealed the NPs' ability to promote GEM's antiproliferative activity to sensitize cells to the effect of TMZ. The findings of this work demonstrate that the developed CH-GEM-NPs are suitable delivery systems for GEM, both as a single therapy and as a chemosensitizer to the GBM gold standard therapy.

Transferrin-Conjugated PLGA Nanoparticles for Co-Delivery of Temozolomide and Bortezomib to Glioblastoma Cells.

Glioblastoma (GBM) represents almost half of primary brain tumors, and its standard treatment with the alkylating agent temozolomide (TMZ) is not curative. Treatment failure is partially related to intrinsic resistance mechanisms mediated by the O6-methylguanine-DNA methyltransferase (MGMT) protein, frequently overexpressed in GBM patients. Clinical trials have shown that the anticancer agent bortezomib (BTZ) can increase TMZ's therapeutic efficacy in GBM patients by downregulating MGMT expression. However, the clinical application of this therapeutic strategy has been stalled due to the high toxicity of the combined therapy. The co-delivery of TMZ and BTZ through nanoparticles (NPs) of poly(lactic-co-glycolic acid) (PLGA) is proposed in this work, aiming to explore their synergistic effect while decreasing the drug's toxicity. The developed NPs were optimized by central composite design (CCD), then further conjugated with transferrin (Tf) to enhance their GBM targeting ability by targeting the blood-brain barrier (BBB) and the cancer cells. The obtained NPs exhibited suitable GBM cell delivery features (sizes lower than 200 nm, low polydispersity, and negative surface charge) and a controlled and sustained release for 20 days. The uptake and antiproliferative effect of the developed NPs were evaluated in in vitro human GBM models. The obtained results disclosed that the NPs are rapidly taken up by the GBM cells, promoting synergistic drug effects in inhibiting tumor cell survival and proliferation. This cytotoxicity was associated with significant cellular morphological changes. Additionally, the biocompatibility of unloaded NPs was evaluated in healthy brain cells, demonstrating the safety of the nanocarrier. These findings prove that co-delivery of BTZ and TMZ in Tf-conjugated PLGA NPs is a promising approach to treat GBM, overcoming the limitations of current therapeutic strategies, such as drug resistance and increased side effects.

Drug Delivery Systems as a Strategy to Improve the Efficacy of FDA-Approved Alzheimer's Drugs.

Alzheimer's disease (AD) is the most common form of dementia, with a high impact worldwide, accounting for more than 46 million cases. The continuous increase of AD demands the fast development of preventive and curative therapeutic strategies that are truly effective. The drugs approved for AD treatment are classified into acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists. The therapeutic effectiveness of those drugs is hindered by their restricted access to the brain due to the blood-brain barrier, low bioavailability, and poor pharmacokinetic properties. In addition, the drugs are reported to have undesirable side effects. Several drug delivery systems (DDSs) have been widely exploited to address these issues. DDSs serve as drug carriers, combining the ability to deliver drugs locally and in a targeted manner with the ability to release them in a controlled and sustained manner. As a result, the pharmacological therapeutic effectiveness is raised, while the unwanted side effects induced by the unspecific distribution decrease. This article reviews the recently developed DDSs to increase the efficacy of Food and Drug Administration-approved AD drugs.

The current state of amyloidosis therapeutics and the potential role of fluorine in their treatment.

Amyloidosis, commonly known as amyloid-associated diseases, is characterized by improperly folded proteins accumulating in tissues and eventually causing organ damage, which is linked to several disorders ranging from neurodegenerative to peripheral diseases. It has an enormous societal and financial impact on the global health sector. Due to the complexity of protein misfolding and intertwined aggregation, there are no effective disease-modifying medications at present, and the condition is likely mis/non-diagnosed half of the time. Nonetheless, over the last two decades, substantial research into aggregation processes has revealed the possibilities of new intervention approaches. On the other hand, fluorine has been a rising star in therapeutic development for numerous neurodegenerative illnesses and other peripheral diseases. In this study, we revised and emphasized the possible significance of fluorine-modified therapeutic molecules and fluorine-modified nanoparticles (NPs) in the modulation of amyloidogenic proteins, including insulin, amyloid beta peptide (Aß), prion protein (PrP), transthyretin (TTR) and Huntingtin (htt).

Interaction of Bortezomib with Cell Membranes Regulates Its Toxicity and Resistance to Therapy.

Bortezomib (BTZ) is a potent proteasome inhibitor currently being used to treat multiple myeloma. However, its high toxicity and resistance to therapy severely limit the treatment outcomes. Drug-membrane interactions have a crucial role in drugs' behavior in vivo, affecting their bioavailability and pharmacological activity. Additionally, drugs' toxicity often occurs due to their effects on the cell membranes. Therefore, studying BTZ's interactions with cell membranes may explain the limitations of its therapy. Due to the cell membranes' complexity, lipid vesicles were proposed here as biomembrane models, focusing on the membrane's main constituents. Two models with distinct composition and complexity were used, one composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and the other containing DMPC, cholesterol (Chol), and sphingomyelin (SM). BTZ's interactions with the models were evaluated regarding the drugs' lipophilicity, preferential location, and effects on the membrane's physical state. The studies were conducted at different pH values (7.4 and 6.5) to mimic the normal blood circulation and the intestinal environment, respectively. BTZ revealed a high affinity for the membranes, which proved to be dependent on the drug-ionization state and the membrane complexity. Furthermore, BTZ's interactions with the cell membranes was proven to induce changes in the membrane fluidity. This may be associated with its resistance to therapy, since the activity of efflux transmembrane proteins is dependent on the membrane's fluidity.

Transferrin Receptor-Targeted Nanocarriers: Overcoming Barriers to Treat Glioblastoma.

Glioblastoma multiforme (GBM) is the most common and lethal type of brain tumor, and the clinically available approaches for its treatment are not curative. Despite the intensive research, biological barriers such as the blood-brain barrier (BBB) and tumor cell membranes are major obstacles to developing novel effective therapies. Nanoparticles (NPs) have been explored as drug delivery systems (DDS) to improve GBM therapeutic strategies. NPs can circumvent many of the biological barriers posed by this devastating disease, enhancing drug accumulation in the target site. This can be achieved by employing strategies to target the transferrin receptor (TfR), which is heavily distributed in BBB and GBM cells. These targeting strategies comprise the modification of NPs' surface with various molecules, such as transferrin (Tf), antibodies, and targeting peptides. This review provides an overview and discussion on the recent advances concerning the strategies to target the TfR in the treatment of GBM, as their benefits and limitations.

Polymeric Nanoparticles-Loaded Hydrogels for Biomedical Applications: A Systematic Review on In Vivo Findings.

Clinically available medications face several hurdles that limit their therapeutic activity, including restricted access to the target tissues due to biological barriers, low bioavailability, and poor pharmacokinetic properties. Drug delivery systems (DDS), such as nanoparticles (NPs) and hydrogels, have been widely employed to address these issues. Furthermore, the DDS improves drugs' therapeutic efficacy while reducing undesired side effects caused by the unspecific distribution over the different tissues. The integration of NPs into hydrogels has emerged to improve their performance when compared with each DDS individually. The combination of both DDS enhances the ability to deliver drugs in a localized and targeted manner, paired with a controlled and sustained drug release, resulting in increased drug therapeutic effectiveness. With the incorporation of the NPs into hydrogels, it is possible to apply the DDS locally and then provide a sustained release of the NPs in the site of action, allowing the drug uptake in the required location. Additionally, most of the materials used to produce the hydrogels and NPs present low toxicity. This article provides a systematic review of the polymeric NPs-loaded hydrogels developed for various biomedical applications, focusing on studies that present in vivo data.

Transferrin-modified nanoparticles for targeted delivery of Asiatic acid to glioblastoma cells.

AIMS: Glioblastoma (GBM) is the most common and deadliest type of brain cancer, and the current therapeutic options are not curative, imposing the need for novel strategies. Asiatic acid (AA) is a natural compound and has been explored due to its anti-glioma activity and lower toxicity to healthy tissues compared with conventional chemotherapeutic agents. However, its poor water-solubility is an obstacle for clinical application. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were proposed in this work for Asiatic acid (AA) delivery. MAIN METHODS: A central composite design was implemented to optimize the NPs, and their surface was further modified with transferrin (Tf), for targeted delivery to GBM cells. The anti-glioma activity of the NPs was studied in vitro using human GBM cells and immortalized human astrocytes. KEY FINDINGS: The NPs exhibited a mean size smaller than 200 nm, with low polydispersity and negative zeta potential, indicating their suitability for brain tumor delivery. The NPs also exhibited high encapsulation efficiency and maintained a slow and controlled release of AA for 20 days. In vitro cell studies showed that NPs were able to maintain the anti-glioma activity of the natural compound and that the surface modification with Tf molecules was able to increase the cellular uptake in GBM cells, enhancing their selectivity and decreasing toxicity in healthy cells. SIGNIFICANCE: Overall, this work provided guidance for designing brain-targeting delivery systems of natural compounds.

Vine Cane Compounds to Prevent Skin Cells Aging through Solid Lipid Nanoparticles.

The long lifespan of the world's population has been raising interest in the research for new solutions to delay the aging process. With the aim of skin aging prevention, solid lipid nanoparticles (SLNs) were developed in this work for the encapsulation of three lipophilic natural compounds extracted from vine cane-epigallocatechin gallate (EGCG), resveratrol and myricetin. The developed loaded-SLNs proved to be stable, maintaining their adequate physicochemical characteristics for 30 days. In addition, the loaded-SLNs formulations exhibited high encapsulation efficiencies and loading capacities and high intracellular antioxidant activity. The mixture of EGCG-loaded SLNs with resveratrol-loaded SLNs proved to have the highest protection against induced oxidative stress. The in vitro cytotoxicity of the loaded SLNs was also evaluated, showing that the developed formulations are biocompatible for concentrations up to 50 µg/mL and could be safe for use in cosmetics. The encapsulation of EGCG, resveratrol and myricetin in SLNs seems to be a suitable strategy for the delivery of these antioxidants to the skin, improving their bioavailability.

Multi-Dose Intravenous Administration of Neutral and Cationic Liposomes in Mice: An Extensive Toxicity Study.

Liposomes are widely used as delivery systems for therapeutic purposes. However, the toxicity associated with the multi-dose administration of these nanoparticles is not fully elucidated. Here, we evaluated the toxicity of the prolonged administration of liposomes composed of neutral or cationic phospholipids often used in drug and gene delivery. For that purpose, adult wild-type mice (C57Bl6) were randomly distributed into three groups receiving either vehicle (PBS), neutral, or cationic liposomes and subjected to repeated intravenous injections for a total of 10 doses administered over 3 weeks. Several parameters, including mortality, body weight, and glucose levels, were monitored throughout the trial. While these variables did not change in the group treated with neutral liposomes, the group treated with the positively charged liposomes displayed a mortality rate of 45% after 10 doses of administration. Additional urinalysis, blood tests, and behavioral assays to evaluate impairments of motor functions or lesions in major organs were also performed. The cationic group showed less forelimb peak force than the control group, alterations at the hematological level, and inflammatory components, unlike the neutral group. Overall, the results demonstrate that cationic liposomes are toxic for multi-dose administration, while the neutral liposomes did not induce changes associated with toxicity. Therefore, our results support the use of the well-known neutral liposomes as safe drug shuttles, even when repetitive administrations are needed.

2020 COVID-19 lockdown and the impacts on air quality with emphasis on urban, suburban and rural zones.

Air quality improvements pollution changes due to COVID-19 restrictions have been reported for many urban developments and large metropolitan areas, but the respective impacts at rural and remote zones are less frequently analysed. This study evaluated air pollution changes across all Portugal (68 stations) considering all urban, suburban and rural zones. PM10, PM2.5, NO2, SO2, ozone was analysed in pre-, during, and post-lockdown period (January-May 2020) and for a comparison also in 2019. NO2 was the most reduced pollutant in 2020, which coincided with decreased traffic. Significant drop (15-71%) of traffic related NO2 was observed specifically during lockdown period, being 55% for the largest and most populated region in country. PM was affected to a lesser degree (with substantial differences found for largely populated areas (Lisbon region ~ 30%; North region, up to 49%); during lockdown traffic-related PM dropped 10-70%. PM10 daily limit was exceeded 50% less in 2020, with 80% of exceedances before lockdown period. SO2 decreased by 35%, due to suspended industrial productions, whereas ozone concentrations slightly (though not significantly) increased (83 vs. 80 µg m-3).

Green tea extract-biomembrane interaction study: The role of its two major components, (-)-epigallocatechin gallate and (-)-epigallocatechin.

The interaction of antioxidants with biological membranes is closely related with their efficacy to inhibit the lipid peroxidation, the cause of several pathologies including cancer, neurodegenerative and cardiovascular disorders. Despite being pointed as a promising antioxidant agent by some authors, the anti-lipid peroxidation of green tea extract (GTE) has not aroused consensus among the scientific community. Since the interaction of drugs with biological membranes plays a key role on their therapeutic activity, this study aims to evaluate the interaction of GTE with liposomes as in vitro biomembrane models composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine phospholipids in the absence and presence of cholesterol (CHOL) (15 mol%). The affinity of GTE and its main components (-)-epigallocatechin gallate (EGCG) and (-)-epigallocatechin (EGC) to the lipid bilayer, their membrane location as well as their effect on the membrane fluidity was investigated by diverse biophysical techniques. Derivative spectrophotometry results proved that GTE has high affinity to the membrane by establishing hydrophobic interactions with the non-polar region of phospholipids and electrostatic interactions with the polar phospholipid heads. Fluorescence and dynamic light scattering data confirm that GTE is located in both hydrophobic and hydrophilic regions of the lipid membrane, therefore affecting the structure of the biomembrane by increasing its fluidity. However, the increased stiffness and organization of the lipid bilayer caused by CHOL significantly affected the interaction of GTE with the membrane. Moreover, the obtained findings suggest a direct contribution of EGCG and EGC on the GTE-membrane interaction.

Caffeic acid for the prevention and treatment of Alzheimer's disease: The effect of lipid membranes on the inhibition of aggregation and disruption of Aß fibrils.

The onset of Alzheimer's disease (AD) is triggered by the aggregation of amyloid ß (Aß) peptides which leads to the formation of fibrils. Molecules that are able to inhibit fibrillation and/or disrupt fibrils have aroused interest for AD therapy. Fibrillation is a complex process highly dependent on the surrounding environment. One of the most relevant factors affecting Aß aggregation is the presence of cellular membranes. Here, the ability of caffeic acid (CA) in preventing the Aß1-42 aggregation and disaggregating mature fibrils was evaluated in a membrane-like environment and in a bulk solution for comparison. To this end, liposomes were used as in vitro models of neuronal membranes. CA exhibited strong activity in inhibiting the fibrillation of Aß1-42 in the aqueous medium, which remained in the presence of liposomes. Furthermore, CA disrupted instantly preformed fibrils in the aqueous medium. However, the CA's disaggregating activity was disturbed by the presence of lipid membranes. Instead of being immediate, the CA's disaggregating activity increased over time. The moderate affinity of CA for the lipid bilayer may explain the distinct fibrils disaggregation profiles. These findings emphasize the therapeutic potential of CA in preventing and treating AD, thus justifying further investigations in animal models.

The interaction of a ß2 adrenoceptor agonist drug with biomimetic cell membrane models: The case of terbutaline sulphate.

Terbutaline sulphate (TS) is a selective short-acting ß2 adrenoceptor agonist used for asthma treatment. The pharmacological activity of TS depends on its binding to the transmembrane protein, ß2 adrenoceptor. Thus, the interactions of this drug with biological membranes are expected, affecting its pharmacological activity. Using in vitro models to study the interaction of TS with biological membranes can provide important information about the activity of the drug. Here, liposomes with different lipid compositions were used as biomimetic models of cell membranes to evaluate the effect of composition, complexity, and physical state of membranes on TS-membrane interactions. For that, liposomes containing dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and liposomes containing DMPC and cholesterol (CHOL) were prepared. For the study of TS-membrane interactions, the TS lipophilicity was evaluated in terms of i) partition coefficient; ii) the preferential location of the drug within the membrane; iii) and the effect of TS on the membrane fluidity. The obtained data suggest that TS has an affinity for the lipid membrane, partitioning from the aqueous to the lipid phase. The affinity was dependent on the liposomes' compositions, showing a greater affinity for DMPC membranes than for DMPC:CHOL model. Dynamic light scattering (DLS) results revealed that this is due to the rigidizing effect caused by CHOL molecules. These findings provide valuable insights in the understanding of the complex interaction of TS with biomembrane models as well as the relevance of lipid compositions and membrane structure in such interactions, which may be related to its pharmacological activity and side effects.