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At the dawn of a new nanotechnological era in the pharmaceutical field, it is very important to examine and understand all the aspects that influence in vivo behaviour of nanoparticles. In this point of view, the interactions between serum proteins and liposomes with incorporated anionic, cationic, and/or PEGylated lipids were investigated to elucidate the role of surface charge and bilayer fluidity in protein corona's formation. 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (DPPC), hydrogenated soybean phosphatidylcholine (HSPC), and 1,2-dioctadecanoyl-sn-glycero-3-phosphocholine (DSPC) liposomes with the presence or absence of 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (sodium salt) (DPPG), 1,2-di-(9Z-octadecenoyl)-3-trimethylammonium-propane (chloride salt) (DOTAP), and/or 1,2-dipalmitoylsn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000] (DPPE-PEG 5000) lipids were prepared by the thin-film hydration method. The evaluation of their biophysical characteristics was enabled by differential scanning calorimetry and dynamic and electrophoretic light scattering. The physicochemical characteristics of mixed liposomes were compared before and after exposure to foetal bovine serum (FBS) and were correlated to calorimetric data. Our results indicate protein binding to all liposomal formulations. However, it is highlighted the importance of surface charge and fluidisation effect to the extent of protein adsorption. Additionally, considering the extensive use of cationic lipids for innovative delivery platforms, we deem PEGylation a key parameter, because even in a small proportion can reduce protein binding, and thus fast clearance and extreme toxicity without affecting positive charge. This study is a continuation of our previous work about protein-liposome interactions and fraction of stealthiness (Fs) parameter, and hopefully a design road map for drug and gene delivery.

Background: Natural and living systems are dynamical systems that demonstrate complex behavior, which appears to be deterministic chaotic, characterized and governed by entropy increase and loss of information throughout their entire lifespan. Lipidic nanoparticles, such as liposomes, as artificial biomembranes, have long been considered appropriate models for studying various membrane phenomena that cell systems exhibit. By utilizing these models, we can better comprehend cellular functions, stability, as well as factors that might alter the cell physiology, leading to severe disease states. In addition, liposomes are well-established drug and vaccine delivery nanosystems, which are present in the market, playing a significant role; therefore, due to their importance, issues concerning their effectiveness and stability are research topics that are constantly investigated and updated. Methods: In this study, the emergent deterministic chaotic behavior of liposomes is described, while evaluation in accordance to their colloidal physical stability, by utilizing established nonlinear dynamics tools, is presented. Two liposomes of different composition and physical stability were developed and a chaotic evaluation on the time series of their size and polydispersity was conducted. Results: The utilized models revealed instability, loss of information and order loss for both liposomes in due time, with important differentiations. An initial interpretation of the results is apposed, whereas the foundations for further investigating possible exploitation of the demonstrated nonlinearity and adaptability of artificial biomembranes is laid, with projection on biosystems. Conclusion: The present approach is expected to impact the application of lipidic nanoparticles and liposomes in various crucial fields, such as drug and vaccine delivery, providing useful information for both the academia and industry.

SQ109 is a tuberculosis drug candidate that has high potency against Mycobacterium tuberculosis and is thought to function at least in part by blocking cell wall biosynthesis by inhibiting the MmpL3 transporter. It also has activity against bacteria and protozoan parasites that lack MmpL3, where it can act as an uncoupler, targeting lipid membranes and Ca2+ homeostasis. Here, we synthesized 19 analogs of SQ109 and tested them against bacteria: M. smegmatis, M. tuberculosis, M. abscessus, Bacillus subtilis and Escherichia coli, as well as against the protozoan parasites, Trypanosoma brucei, T. cruzi, Leishmania donovani, L. mexicana and Plasmodium falciparum. Activity against the mycobacteria was generally less than with SQ109 and was reduced by increasing the size of the alkyl adduct, but two analogs were ~4-8 fold more active than was SQ109 against M. abscessus, including a highly drug resistant strain harboring a A309P mutation in MmpL3. There was also better activity than found with SQ109 with other bacteria and protozoa. Of particular interest, we found that the adamantyl C-2 ethyl, butyl, phenyl and benzyl analogs had 4-10x increased activity against P. falciparum asexual blood stages, together with low toxicity to a human HepG2 cell line, making them of interest as new anti-malarial drug leads. We also used surface plasmon resonance to investigate the binding of inhibitors to MmpL3, and differential scanning calorimetry to investigate binding to lipid membranes. There was no correlation between MmpL3 binding and M. tuberculosis or M. smegmatis cell activity, suggesting that MmpL3 is not a major target, in mycobacteria. However, some of the more active species decreased lipid phase transition temperatures, indicating increased accumulation in membranes, expected to lead to enhanced uncoupler activity.

Aim: Coronaviruses well studied in the past provide scientific tools and knowledge that is used for identifying the molecular basis of the new SARS-CoV-2. It belongs to complex systems and its evolution and mutations must be observed under the lens of the nonlinearity as it is far from the equilibrium conditions. The new properties that SARS-CoV-2 carries were incubated for a long time in microcosm refining its information content. Various animal species acted as transmitters of SARS-CoV-2 to human beings. In this perspective article, we argue that the infection ability of the new virus can correlate with its thermodynamic payload. Design: We suggest that by identifying the thermodynamic content and biophysical profile of the viruses’ proteins using a mathematical framework of nonlinear complex systems, we can simulate its molecular origin and design weapons for fighting it. We suggest discovering for artificial ‘decision-making’ nano-platforms that can decrypt the ‘crypted information code’ of viruses that permit their mutation process taking place not randomly but based on the self-assembly process of its nucleotides following the micro and macro environmental conditions. Main outcomes: This concept needs generous funding by governments for supporting intelligence and innovative research projects. Mainly, we need solidarity between nations to shield the health of societies.

The abilities of sub-cellular targeting and stimuli-responsiveness are critical challenges in pharmaceutical nanotechnology. In the present study, glyceryl monooleate (GMO)-based non-lamellar lyotropic liquid crystalline nanoparticles were stabilized by the poly(2-(dimethylamino)ethyl methacrylate)-b-poly(lauryl methacrylate) block copolymer carrying tri-phenyl-phosphine cations (TPP-QPDMAEMA-b-PLMA), either used alone or in combination with other polymers as co-stabilizers. The systems were designed to perform simultaneously sub-cellular targeting, stimuli-responsiveness and to exhibit stealthiness. The physicochemical characteristics and fractal dimensions of the resultant nanosystems were obtained from light scattering techniques, while their micropolarity and microfluidity from fluorescence spectroscopy. Their morphology was assessed by cryo-TEM, while their thermal behavior by microcalorimetry and high-resolution ultrasound spectroscopy. The analyzed properties, including the responsiveness to pH and temperature, were found to be dependent on the combination of the polymeric stabilizers. The subcellular localization was monitored by confocal microscopy, revealing targeting to lysosomes. Subsequently, resveratrol was loaded into the nanosystems, the entrapment efficiency was investigated and in vitro release studies were carried out at different conditions, in which a stimuli-triggered drug release profile was achieved. In conclusion, the proposed multi-functional nanosystems can be considered as potentially stealth, stimuli-responsive drug delivery nanocarriers, with targeting ability to lysosomes and presenting a stimuli-triggered drug release profile.

Quercetin (Que) is a flavonoid associated with high oxygen radical scavenging activity and potential neuroprotective activity against Alzheimer's disease. Que's oral bioavailability is limited by its low water solubility and extended peripheral metabolism; thus, nasal administration may be a promising alternative to achieve effective Que concentrations in the brain. The formation of Que-2-hydroxypropylated-β-cyclodextrin (Que/HP-β-CD) complexes was previously found to increase the molecule's solubility and stability in aqueous media. Que-methyl-β-cyclodextrin (Que/Me-β-CD) inclusion complexes were prepared, characterized, and compared with the Que/HP-β-CD complex using biophysical and computational methods (phase solubility, fluorescence and NMR spectroscopy, differential scanning calorimetry (DSC), and molecular dynamics simulations (MDS)) as candidates for the preparation of nose-to-brain Que's delivery systems. DSC thermograms, NMR, fluorescence spectroscopy, and MDS confirmed the inclusion complex formation of Que with both CDs. Differences between the two preparations were observed regarding their thermodynamic stability and inclusion mode governing the details of molecular interactions. Que's solubility in aqueous media at pH 1.2 and 4.5 was similar and linearly increased with both CD concentrations. At pH 6.8, Que's solubility was higher and positively deviated from linearity in the presence of HP-β-CD more than with Me-β-CD, possibly revealing the presence of more than one HP-β-CD molecule involved in the complex. Overall, water solubility of lyophilized Que/Me-β-CD and Que/HP-β-CD products was approximately 7-40 times and 14-50 times as high as for pure Que at pH 1.2-6.8. In addition, the proof of concept experiment on ex vivo permeation across rabbit nasal mucosa revealed measurable and similar Que permeability profiles with both CDs and negligible permeation of pure Que. These results are quite encouraging for further ex vivo and in vivo evaluation toward nasal administration and nose-to-brain delivery of Que.

Irbesartan (IRB) exerts beneficial effects either alone or in combination with other drugs on numerous diseases, such as cancer, diabetes, and hypertension. However, due to its high lipophilicity, IRB does not possess the optimum pharmacological efficiency. To circumvent this problem, a drug delivery system with 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD) was explored. The 1:1 complex between IRB and 2-HP-β-CD was identified through ESI QTF HRMS. Dissolution studies showed a higher dissolution rate of the lyophilized IRB-2-HP-β-CD complex than the tablet containing IRB at pH = 1.2. DSC results revealed the differences of the thermal properties between the complex and various mixtures consisting of the two components, namely IRB and 2-HP-β-CD. Interestingly, depending on the way the mixture preparation was conducted, different association between the two components was observed. Molecular dynamics (MD) simulations predicted the favorable formation of the above complex and identified the dominant interactions between IRB and 2-HP-β-CD. In vitro pharmacological results verified that the inclusion complex not only preserves the binding affinity of IRB for AT1R receptor, but also it slightly increases it. As the complex formulation lacks the problems of the tablet, our approach is a promising new way to improve the efficiency of IRB.

Liposomes and lipidic vehicles are nanotechnological platforms that are present in the clinic and industry, with extensive application and much potential in the field of therapeutics. Currently, the obstacles associated with the pathology and physiology of Alzheimer's disease (AD) and neurodegenerative disorders (NDDs) in general have rendered it impossible to find an effective therapy for these conditions. The only achievement of the available drugs and treatments is that they have succeeded in temporarily alleviating the symptoms and assisting patients in carrying on with their activities of daily living, but they do not delay, let alone halt, the progression of the diseases. So far, numerous small drug molecules and biological molecules have failed in clinical trials. Liposomes represent a promising option for drug delivery that have yet to be tested in clinical trials. They are manufactured by many different and versatile techniques. Their contribution in AD regards mainly the delivery of bioactive agents in a targeted and controlled manner through the blood-brain barrier and into the brain, with the ultimate goal to block the β-amyloid (Aβ) and/or tau aggregation. Their flexibility and biocompatibility as platforms, combined with their ability to protect the encapsulated/incorporated molecules, are advantages that are expected to assist this endeavor.

The fields of medicine and therapeutics have lately turned towards more modern approaches for the therapy of diseases. These approaches have been classified as new health technologies and various issues that regard their development, application in therapy, regulatory framework, approval and post-approval monitoring have emerged. In the European environment, the law and legislation distinguish new health technologies in certain subcategories, namely, medicinal products, medical devices, biotechnological products, advanced therapy medicinal products and nanomedicinal products. Among these strategies, nanomedicine utilizes entities at the nanoscale that exhibit therapeutic effect in various diseases, such as neurodegenerative disorders, through chemical, physical or biological action. Several nanotechnology-based therapies have been authorized until today; however, there is still no marketed nanomedicine for neurodegenerative diseases. Advanced nanotechnological platforms, including the prominent example of stimuli-responsive chimeric/mixed nanocarriers, promise high therapeutic efficacy and safety, through their functional properties and biocompatibility, which come from their composing molecules, self-assembled properties and supramolecular structures. The integration of certain important analytical tools for the study of nanocarriers is also of great importance and may provide knowledge for further development of advanced nanomedicines as well as for their follow-on products, known as "nanosimilars".

The aim of the present study is the development and evaluation of the physicochemical properties of chimeric hydrogenated soya phosphatidylcholine (HSPC) and egg phosphatidylcholine (EggPC) liposomes with incorporated triblock copolymer Poloxamer P407 (P407). The physicochemical assay was held in water HPLC-grade and Foetal Bovine Serum (FBS), in order to determine whether these systems can be used as drug or antigen delivery nanosystems. Dynamic and electrophoretic light scattering (DLS/ELS) techniques were used for the measurement of the hydrodynamic diameter, the polydispersity index, and the ζ-potential of the prepared nanosystems. The incorporation of the P407 resulted in a size reduction of all systems. A decrease in the hydrodynamic diameter and polydispersity index were also found as a result of increasing the storage temperature from 4 °C to 25 °C, attributed to P407. The experiments that were carried out in FBS, showed that the addition of P407 improved systems stealth properties. Concluding, we propose P407 as a promising alternative to PEG in the development of lipid nanoparticles with optimized bio- and shelf-stability.

The investigation of properties of amphiphilic block copolymers as stabilizers for non-lamellar lyotropic liquid crystalline nanoparticles represents a fundamental issue for the formation, stability and upgraded functionality of these nanosystems. The aim of this work is to use amphiphilic block copolymers, not studied before, as stabilizers of glyceryl monooleate 1-(cis-9-octadecenoyl)-rac-glycerol (GMO) colloidal dispersions. Nanosystems were prepared with the use of poly(ethylene oxide)-b-poly(lactic acid) (PEO-b-PLA) and poly(ethylene oxide)-b-poly(5-methyl-5-ethyloxycarbonyl-1,3-dioxan-2-one) (PEO-b-PMEC) block copolymers. Different GMO:polymer molar ratios lead to formulation of nanoparticles with different size and internal organization, depending on the type of hydrophobic block. Resveratrol was loaded into the nanosystems as a model hydrophobic drug. The physicochemical and morphological characteristics of the prepared nanosystems were investigated by dynamic light scattering (DLS), cryogenic transmission electron microscopy (cryo-TEM), fast Fourier transform (FFT) analysis and X-ray diffraction (XRD). The studies allowed the description of the lyotropic liquid crystalline nanoparticles and evaluation of impact of copolymer composition on these nanosystems. The structures formed in GMO:block copolymer colloidal dispersions were compared with those discussed previously. The investigations broaden the toolbox of polymeric stabilizers for the development of this type of hybrid polymer/lipid nanostructures.

Chimeric or mixed nanosystems belong to the class of advanced therapeutics. Their distinctive characteristic compared with other types of nanoparticles is that they combine two or more different classes of biomaterials. These platforms have created a promising and versatile field of nanomedicine, incorporating materials that are biocompatible, such as lipids, but also functional, such as stimuli-responsive polymers. In the present work, thermoresponsive chimeric nanocarriers composed of l -α-phosphatidylcholine (Egg, Chicken) (EPC) phospholipids and poly(N-isopropylacrylamide)-b-poly(lauryl acrylate) (PNIPAM-b-PLA) block copolymers were designed and developed. Initially, model lipid bilayers with incorporated polymers and drug molecule TRAM-34 were built and studied for their thermodynamics, in order to assess the stability and functionality of the systems. Chimeric nanoparticles of EPC and PNIPAM-b-PLA were then developed and evaluated for their physicochemical properties in different medium conditions, as well as for their morphology. Polymer incorporation led to alterations in the properties and morphology of the nanoparticles, while interactions with serum proteins were absent. TRAM-34 was also incorporated inside the developed nanocarriers, followed by incorporation and release studies, which revealed the functionality of the system in elevated temperature conditions. Finally, in vitro studies on normal cells suggest the biocompatibility of these nanosystems. The proposed platforms are promising for further studies and applications in vitro and in vivo.

Nanocarriers are delivery platforms of drugs, peptides, nucleic acids and other therapeutic molecules that are indicated for severe human diseases. Gliomas are the most frequent type of brain tumor, with glioblastoma being the most common and malignant type. The current state of glioma treatment requires innovative approaches that will lead to efficient and safe therapies. Advanced nanosystems and stimuli-responsive materials are available and well-studied technologies that may contribute to this effort. The present study deals with the development of functional chimeric nanocarriers composed of a phospholipid and a diblock copolymer, for the incorporation, delivery and pH-responsive release of the antiglioma agent TRAM-34 inside glioblastoma cells. Nanocarrier analysis included light scattering, protein incubation and electron microscopy, and fluorescence anisotropy and thermal analysis techniques were also applied. Biological assays were carried out in order to evaluate the nanocarrier nanotoxicity in vitro and in vivo, as well as to evaluate antiglioma activity. The nanosystems were able to successfully manifest functional properties under pH conditions, and their biocompatibility and cellular internalization were also evident. The chimeric nanoplatforms presented herein have shown promise for biomedical applications so far and should be further studied in terms of their ability to deliver TRAM-34 and other therapeutic molecules to glioblastoma cells.

Thermoresponsive nanomaterials have led to a plethora of new applications in the fields of Nanobiotechnology, Biomedicine and Therapeutics. Since liposomal membranes are lyotropic liquid crystals, the development of thermoresponsive liposomes for drug delivery has been recognized as an attractive scientific field. Additionally, plenty of studies utilizing the temperature-dependent response of certain synthetic polymers are conducted, alone or in combination with liposomes. In the present study, we combined the liposomal and thermoresponsive polymer technologies, in order to create functional chimeric/mixed liposomal nanosystems with innovative properties. Initially, differential scanning calorimetry was applied on chimeric/mixed bilayers to evaluate the effect of polymeric guests on the thermotropic behavior of lipidic membranes. Thereafter, chimeric/mixed liposomes were built and their physicochemical properties, as well as their colloidal stability were measured and evaluated. The nature of the self-assembled structures and the lipidic membrane morphology were investigated through cryo-transmission electron microscopy, while their thermoresponsiveness and its consequences on the lipidic membrane properties were assessed, through a simple heating protocol. The presence of a new thermodynamic phase on the lipidic membrane acts as an agglomeration and aggregation inducer, affecting the whole colloidal chimeric/mixed nanosystem. This mechanism might be characterized as “phase functionality” and may be utilized for drug delivery purposes and also in other applications. Biophysics and thermodynamics are very important tools to study the self-assembly process, as well as the stability and bio-functionality of drug delivery systems.

Background: The incorporation of polymeric components into liposomes promotes structural rearrangement of the lipid bilayers that could affect their properties and their behavior. Therefore, by mixing phospholipids with polymeric compounds the, socalled chimeric liposomal nanosystems are produced and could be advantageous, compared with conventional (e.g. composed of pure phospholipids) liposomal nanostructures. Objective: In this work, we used lipids with different main transition temperature (Tm) i.e 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC, Tm=55°C), L-α-phosphatidylcholine, hydrogenated (Soy) (HSPC, Tm=52 °C) and egg phosphatidylcholine (EggPC, Tm=23 °C) and we studied and compared the physicochemical characteristics and the stability of conventional with that of chimeric liposomes. Methods: Thin-film hydration method (TFH) was used as the preparation protocol for all systems. Dynamic and electrophoretic light scattering (DLS and ELS) were utilized in order to elucidate the physicochemical characteristics of all systems. All liposomal systems exhibited sizes below 100nm while the ζ-potential was around zero, indicating the absence of surface charge. Results: The results revealed that the Tm of each phospholipid influences the biophysical behavior of the lipidic membrane, which contributes to the physicochemical characteristics and affects the physical stability of the liposomal nanosystems. The nature and physicochemical properties of each phospholipid seem to play a key role, regarding the structural characteristics and the formation process of the liposomal nanosystems. Conclusion: : Comparing the physicochemical properties of the conventional liposomes with those of the chimeric liposomal systems, we conclude that the complexity of the latter, due to the incorporation of the polymeric guest into the lipidic bilayer, revealed new properties, which correspond to increased physical stability.

The aim of the present study is to investigate the interactions between liposomes and proteins and to evaluate the role of liposomal lipid composition and concentration in the formation of protein corona. Liposomes composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or hydrogenated soybean phosphatidylcholine (HSPC) with 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (sodium salt) (DPPG), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000] (DPPE-PEG 3000), cholesterol (CH) or mixtures of these lipids, were prepared at different concentrations by the thin-film hydration method. After liposomes were dispersed in HPLC-grade water and foetal bovine serum (FBS), their physicochemical characteristics, such as size, size distribution, and ζ-potential, were determined using dynamic and electrophoretic light scattering. Aggregation of DPPC, HSPC, DPPC:CH (9:1 molar ratio), and HSPC:CH (9:1 molar ratio) in FBS was observed. On the contrary, liposomes incorporating DPPG lipids and CH both in a molar ratio of 11% were found to be stable over time, while their size did not alter dramatically in biological medium. Liposomes containing CH and PEGylated lipids retain their size in the presence of serum as well as their physical stability. In addition, our results indicate that the protein binding depends on the presence of polyethylene glycol (PEG), CH, concentration and surface charge. In this paper, we introduce a new parameter, fraction of stealthiness (Fs), for investigating the extent of protein binding to liposomes. This parameter depends on the changes in size of liposomes after serum incubation, while liposomes have stealth properties when Fs is close to 1. Thus, we conclude that lipid composition and concentration affect the adsorption of proteins and the liposomal stabilization.

Niosomes belong to drug delivery systems and consist mainly of non-ionic surfactants and cholesterol. In this study, we designed and developed systems composed of non-ionic surfactants i.e. Tween 80, Span 80 and cholesterol with and without poly(ethylene oxide)-b-poly(ε-caprolactone) (PEO-b-PCL) block copolymer, using different molar ratios of the above components. The nanosystems were formed by the thin-film hydration method with purified water as dispersion medium. Several physicochemical techniques were utilized in order to study the physicochemical and morphological characteristics of the prepared assemblies. The results showed that the presence of the block copolymer alters significantly the size and morphology of neat surfactant/cholesterol niosomes. The ageing studies also revealed that the stability is strongly dependent on the nature and the molar ratios of the components. Moreover, neither of the studied nanosystems exhibited elevated signs of cellular toxicity in vitro nor acute systemic toxicity in vivo short-term experiments. This investigation covers a new field of drug delivery platforms those of niosomes composed by different biomaterials i.e. surfactants and block copolymers.

Oleocanthal, oleacein, oleuropein and hydroxytyrosol comprise characteristic polyphenols of olive with high biological value. However, stability problems hinder their further investigation. Thus, in the present study they were incorporated in nanoliposomes by thin film hydration method. The particles sizes, PDI, zeta-potential and physicochemical stabilities of nanoliposomes were evaluated by light scattering methods while FTIR, XRD, TGA and DSC methods were carried out for further physicochemical characterization. Their micromorphology was illustrated by negative-staining TEM and Cryo-TEM, revealing well-dispersed round-shaped vesicles. According to in vitro release studies, oleocanthal and oleacein were rapidly released in a higher percentage than oleuropein and hydroxytyrosol and compatible with the Ritger-Peppas model release mechanism while only oleuropein liposomes were governed by anomalous diffusion of non-Fickian diffusion. Antioxidant assays showed that nanoliposomes presented comparable activity with pure compounds enabling them as suitable carriers for the delivery of olive active biophenols in the human organism.

Amphiphilic polymers represent one of the main class of stabilizers for non-lamellar lyotropic liquid crystalline nanoparticles, being essential for their formation and stability. In the present study, poly(ethylene oxide)-block-poly(e-caprolactone) (PEO-b-PCL) block copolymers and poly(2-methyl-2-oxazoline)-grad-poly(2-phenyl-2-oxazoline) (MPOx) gradient copolymers were incorporated as stabilizers in liquid crystalline nanoparticles prepared from glyceryl monooleate. The polymers were chosen according to their high biocompatibility and promising stealth properties, in order to develop safe and efficient drug delivery nanosystems. The physicochemical characteristics and fractal dimension of the resultant nanosystems were obtained from light scattering techniques, while their micropolarity and microfluidity from fluorescence spectroscopy. The effect of temperature, serum proteins and ionic strength on the physicochemical behavior was monitored. Their morphology was assessed by cryo-TEM, while their thermal behavior by microcalorimetry and high-resolution ultrasound spectroscopy. Their properties were dependent on the stabilizer chemistry and topology (block/gradient copolymer) and its concentration. Subsequently, resveratrol, as model hydrophobic drug, was loaded into the nanosystems, the entrapment efficiency was calculated and in vitro release studies were carried out, highlighting how the different stabilizer can differentiate the drug release profile. In conclusion, the proposed copolymers broaden the toolbox of polymeric stabilizers for the development of liquid crystalline nanoparticles intended for drug delivery applications.