Late relapse after CAR-T cell therapy for adult patients with hematologic malignancies: A definite evidence from systematic review and meta-analysis on individual data.

Chimeric Antigen Receptor (CAR)-modified T lymphocytes represent one of the most innovative and promising approaches to treating hematologic malignancies. CAR-T cell therapy is currently being used for the treatment of relapsed/refractory (r/r) B-cell malignancies including Acute Lymphoblastic Leukemia, Large B-Cell Lymphoma, Follicular Lymphoma, Multiple Myeloma and Mantle Cell Lymphoma. Despite the unprecedented clinical success, one of the major issues of the approved CAR-T cell therapy - tisagenlecleucel, axicabtagene, lisocabtagene, idecabtagene, ciltacabtagene and brexucabtagene - is the uncertainty about its persistence which in turn could lead to weak or no response to therapy with malignancy recurrence. Here we show that the prognosis of patients who do not respond to CAR-T cell therapy is still an unmet medical need. We performed a systematic review and meta-analysis collecting individual data on Duration of Response from at least 12-month follow-up studies. We found that the pooled prevalence of relapse within the first 12 months after CAR-T infusion was 61% (95% CI, 43%-78%); moreover, one year after the infusion, the analysis highlighted a pooled prevalence of relapse of 24% (95% CI, 11%-42%). Our results suggest that identifying potential predictive biomarkers of response to CAR-T therapy, especially for patients affected by the advanced stage of blood malignancies, could lead to stratification of the eligible population to that therapy, recognizing which patients will benefit and which will not, helping regulators to make decision in that way.

In Situ Swelling Formulation of Glycerol-Monooleate-Derived Lyotropic Liquid Crystals Proposed for Local Vaginal Application.

Hydrogels have been extensively investigated to identify innovative formulations that can fulfill all the necessary purposes to improve local vaginal therapy through the mucosa. Herein, we propose in situ-forming lyotropic liquid crystals (LLCs) derived from a cheap and GRAS (generally recognized as safe) ingredient as an intravaginal delivery system. The system consists of a precursor solution loaded with sertaconazole nitrate as a model drug, which is able to easily swell in a stable three-dimensional structure by absorbing simulated vaginal fluid. Under polarized light microscopy the precursor solution and the formed phase of LLCs showed the typical textures belonging to anisotropic and an isotropic mesophases, respectively. A deep rheological investigation by Kinexus® Pro proved the stability and strength of the cubic phase, as well as its potential in mucoadhesion. In vitro degradation studies showed a slow matrix erosion, consistent with data obtained from lipophilic drug release studies in simulated vaginal fluid. Therefore, the suggested cubic phase based on lyotropic liquid crystals could represent a valid proposal as a vaginal drug delivery system due to its characteristics of resistance, adhesion and the possibility of providing a slow and controlled release of drugs directly at the administration site.

A comparison between silicone-free and silicone-based emulsions: Technological features and in vivo evaluation.

OBJECTIVE: Nowadays, the use of silicones in cosmetic formulation is still controversial, given that "natural" or "biodegradable" components are preferred. Often, the exclusion and/or the discrimination of these excipients from cosmetic field are unmotivated because all things cannot be painted with the same brush. Hence, we want to bring to light and underline the advantages of including silicones in cosmetic emulsions, refuting and debunking some myths related to their use. METHODS: Silicone-free and silicone-based emulsions were obtained within an easy homogenization process. Droplet size distribution was assessed by laser diffraction particle size analyser Mastersizer 2000™, and by optical microscopy. The long-time stability profiles were investigated thanks to the optical analyser Turbiscan® Lab Expert. Diffusing wave spectroscopy (DWS) by Rheolaser Master™ and frequency sweep measurements by Kinexus® Pro Rotational Rheometer were carried out to assess a full rheological characterization. In vivo studies were carried out by the evaluation of Trans Epidermal Water Loss (TEWL) over time on healthy human volunteers. A skin feeling rating was collected from the same volunteers by questionnaire. RESULTS: From size distribution analysis, a better coherence of data appeared for silicone-based emulsion, as the size of the droplets was kept unchanged after 1 month, as well as the uniformity parameter. Morphological investigation confirmed a homogenous droplet distribution for both samples. Silicones enhanced the viscosity, compactness and strength of the cream, providing a suitable stability profile both at room temperature and when heated at 40°C. The solid-like viscoelastic behaviour was assessed in the presence of dynamic oscillatory stresses. The monitoring of TEWL over time demonstrated non-occlusive properties of emulsions containing silicones, the values of which were comparable to the negative control. Silicone-based emulsions gained higher scores from the volunteers in silkiness, freshness and softness features, while lower scores were obtained in greasiness compared to silicone-free emulsions. No cases of irritation were recorded by the candidates. CONCLUSION: The presence of specific silicones inside a cosmetic product improved its technological characteristics. The rheological identity and the stability feature showed the real suitability of prepared emulsion as a cosmetic product. Moreover, this study demonstrated that silicone-based emulsions are safe for the skin and did not cause skin occlusion. Improved skin sensations are registered by potential consumers when silicones are included in the formulation.

OBJECTIF: De nos jours, l'utilisation de silicones dans la formulation cosmétique reste controversée, étant donné que les ingrédients «naturels¼ ou «biodégradables¼ sont privilégiés. Souvent, l'exclusion et/ou la discrimination de ces excipients du domaine cosmétique ne sont pas motivées, parce que tous les éléments ne peuvent pas être logés à la même enseigne. Par conséquent, nous souhaitons mettre en évidence et souligner les avantages de l'inclusion des silicones dans les émulsions cosmétiques, tout en réfutant et en démystifiant certains mythes liés à leur utilisation. MÉTHODES: Des émulsions sans silicone et des émulsions à base de silicone ont été obtenues dans le cadre d'un processus d'homogénéisation facile. La distribution des tailles de gouttelettes a été évaluée par diffraction laser avec le granulomètre Mastersizer 2000™ et par microscopie optique. Les profils de stabilité à long terme ont été étudiés grâce à l'analyseur optique Turbiscan® Lab Expert. La spectroscopie par diffusion d'ondes (Diffusing Wave Spectroscopy, DWS) par le Rheolaser Master™ et les mesures de balayage de fréquence par le rhéomètre rotatif Kinexus® Pro ont été réalisées pour évaluer une caractérisation rhéologique complète. Des études in vivo ont été menées par le biais de l'évaluation de la perte d'eau transépidermique (PETE) au fil du temps sur des volontaires humains en bonne santé. Une évaluation de la sensation cutanée a été recueillie auprès des mêmes volontaires par le biais d'un questionnaire. RÉSULTATS: L'analyse de la distribution des tailles a révélé une meilleure cohérence des données pour l'émulsion à base de silicone, car la taille des gouttelettes a été maintenue inchangée après 1 mois, ainsi que le paramètre d'uniformité. L'investigation morphologique a confirmé une distribution homogène des gouttelettes pour les deux échantillons. Les silicones ont amélioré la viscosité, la densité et la résistance de la crème, offrant ainsi un profil de stabilité approprié aussi bien à température ambiante qu'après chauffage à 40°C. Le comportement viscoélastique analogue à celui d'un solide a été évalué en présence de contraintes oscillatoires dynamiques. Le suivi de la perte d'eau transépidermique (PETE) au fil du temps a établi des propriétés non occlusives des émulsions contenant des silicones, dont les valeurs étaient comparables à celles du contrôle négatif. Les émulsions à base de silicone ont obtenu des scores plus élevés chez les volontaires en termes de caractéristiques de douceur, de fraîcheur et de souplesse, tandis que des scores plus faibles ont été obtenus en termes d'onctuosité par rapport aux émulsions sans silicone. Aucun cas d'irritation n'a été enregistré chez les candidats. CONCLUSION: La présence de silicones spécifiques dans un produit cosmétique a amélioré ses caractéristiques technologiques. L'identité rhéologique et la caractéristique de stabilité ont montré la pertinence réelle d'une émulsion préparée en tant que produit cosmétique. De plus, cette étude a démontré que les émulsions à base de silicone sont sans danger pour la peau et n'ont provoqué aucune occlusion cutanée. Les consommateurs potentiels enregistrent une amélioration des sensations cutanées lorsque des silicones sont inclus dans la formulation.

Atrial myxomas arise from multipotent cardiac stem cells.

AIMS: Cardiac myxomas usually develop in the atria and consist of an acid-mucopolysaccharide-rich myxoid matrix with polygonal stromal cells scattered throughout. These human benign tumours are a valuable research model because of the rarity of cardiac tumours, their clinical presentation and uncertain origin. Here, we assessed whether multipotent cardiac stem/progenitor cells (CSCs) give rise to atrial myxoma tissue. METHODS AND RESULTS: Twenty-three myxomas were collected and analysed for the presence of multipotent CSCs. We detected myxoma cells positive for c-kit (c-kitpos) but very rare Isl-1 positive cells. Most of the c-kitpos cells were blood lineage-committed CD45pos/CD31pos cells. However, c-kitpos/CD45neg/CD31neg cardiac myxoma cells expressed stemness and cardiac progenitor cell transcription factors. Approximately ≤10% of the c-kitpos/CD45neg/CD31neg myxoma cells also expressed calretinin, a characteristic of myxoma stromal cells. In vitro, the c-kitpos/CD45neg/CD31neg myxoma cells secrete chondroitin-6-sulfate and hyaluronic acid, which are the main components of gelatinous myxoma matrix in vivo. In vitro, c-kitpos/CD45neg/CD31neg myxoma cells have stem cell properties being clonogenic, self-renewing, and sphere forming while exhibiting an abortive cardiac differentiation potential. Myxoma-derived CSCs possess a mRNA and microRNA transcriptome overall similar to normal myocardium-derived c-kitpos/CD45neg/CD31negCSCs , yet showing a relatively small and relevant fraction of dysregulated mRNA/miRNAs (miR-126-3p and miR-335-5p, in particular). Importantly, myxoma-derived CSCs but not normal myocardium-derived CSCs, seed human myxoma tumours in xenograft's in immunodeficient NOD/SCID mice. CONCLUSION: Myxoma-derived c-kitpos/CD45neg/CD31neg CSCs fulfill the criteria expected of atrial myxoma-initiating stem cells. The transcriptome of these cells indicates that they belong to or are derived from the same lineage as the atrial multipotent c-kitpos/CD45neg/CD31neg CSCs. Taken together the data presented here suggest that human myxomas could be the first-described CSC-related human heart disease.

Influence of Materials Properties on Bio-Physical Features and Effectiveness of 3D-Scaffolds for Periodontal Regeneration.

Periodontal diseases are multifactorial disorders, mainly due to severe infections and inflammation which affect the tissues (i.e., gum and dental bone) that support and surround the teeth. These pathologies are characterized by bleeding gums, pain, bad breath and, in more severe forms, can lead to the detachment of gum from teeth, causing their loss. To date it is estimated that severe periodontal diseases affect around 10% of the population worldwide thus making necessary the development of effective treatments able to both reduce the infections and inflammation in injured sites and improve the regeneration of damaged tissues. In this scenario, the use of 3D scaffolds can play a pivotal role by providing an effective platform for drugs, nanosystems, growth factors, stem cells, etc., improving the effectiveness of therapies and reducing their systemic side effects. The aim of this review is to describe the recent progress in periodontal regeneration, highlighting the influence of materials' properties used to realize three-dimensional (3D)-scaffolds, their bio-physical characteristics and their ability to provide a biocompatible platform able to embed nanosystems.

Rutin-Loaded Solid Lipid Nanoparticles: Characterization and In Vitro Evaluation.

This study was aimed at preparing and characterizing solid lipid nanoparticles loading rutin (RT-SLNs) for the treatment of oxidative stress-induced diseases. Phospholipon 80H® as a solid lipid and Polysorbate 80 as surfactant were used for the SLNs preparation, using the solvent emulsification/diffusion method. We obtained spherical RT-SLNs with low sizes, ranging from 40 to 60 nm (hydrodynamic radius) for the SLNs prepared starting from 2% and 5% (w/w) theoretical amount. All prepared formulations showed negative zeta-potential values. RT was efficiently encapsulated within SLNs, obtaining high encapsulation efficiency and drug content percentages, particularly for SLNs prepared with a 5% theoretical amount of RT. In vitro release profiles and analysis of the obtained data applying different kinetic models revealed Fickian diffusion as the main mechanism of RT release from the SLNs. The morphology of RT-SLNs was characterized by scanning electron microscopy (SEM), whereas the interactions between RT and the lipid matrix were investigated by Raman spectroscopy, evidencing spectral modifications of characteristic bands of RT due to the establishment of new interactions. Finally, antioxidant activity assay on human glioblastoma astrocytoma (U373) culture cells showed a dose-dependent activity for RT-SLNs, particularly at the highest assayed dose (50 µM), whereas the free drug showed the lesser activity.

Poly(ethyl acrylate-co-methyl Methacrylate-co-trimethylammoniethyl methacrylate chloride) (Eudragit RS100) Nanocapsules as Nanovector Carriers for Phoenix dactylifera L. Seeds Oil: a Versatile Antidiabetic Agent.

Food waste valorization practices have gained considerable attention focusing on the conversion of the waste into valuable products. In this context, the present study provides an insight into a new Eudragit RS100 based nanosystem as a carrier of date palm (Phoenix dactylifera L.) seeds oil known for its an antidiabetic activity. A priori systematic study was carried out in order to understand the individual impact of all contributing factors considered by the nanoprecipitation method. Then, date seeds oil nanoparticles were prepared, characterized and analyzed for their in vitro inhibition activity against: α-amylase and α-glucosidase. The results showed that the developed nanoparticles had an average diameter around 207 nm, a ζ-potential of +59 mV, and an encapsulation efficiency equal to 97 ± 1% with a loading capacity of 0.48 mg·mg-1. The α-amylase and α-glucosidase IC50 were found to be 87.6 and 155.3 µg·mL-1, respectively. Therefore, this study may surely open new perspectives for the development of novel health-promoting plant oils loaded-nanocarriers for several purposes.

Cardiac Stem Cell-Loaded Delivery Systems: A New Challenge for Myocardial Tissue Regeneration.

Cardiovascular disease (CVD) remains the leading cause of death in Western countries. Post-myocardial infarction heart failure can be considered a degenerative disease where myocyte loss outweighs any regenerative potential. In this scenario, regenerative biology and tissue engineering can provide effective solutions to repair the infarcted failing heart. The main strategies involve the use of stem and progenitor cells to regenerate/repair lost and dysfunctional tissue, administrated as a suspension or encapsulated in specific delivery systems. Several studies demonstrated that effectiveness of direct injection of cardiac stem cells (CSCs) is limited in humans by the hostile cardiac microenvironment and poor cell engraftment; therefore, the use of injectable hydrogel or pre-formed patches have been strongly advocated to obtain a better integration between delivered stem cells and host myocardial tissue. Several approaches were used to refine these types of constructs, trying to obtain an optimized functional scaffold. Despite the promising features of these stem cells' delivery systems, few have reached the clinical practice. In this review, we summarize the advantages, and the novelty but also the current limitations of engineered patches and injectable hydrogels for tissue regenerative purposes, offering a perspective of how we believe tissue engineering should evolve to obtain the optimal delivery system applicable to the everyday clinical scenario.

Influence of Various Model Compounds on the Rheological Properties of Zein-Based Gels.

The controlled release of a compound entrapped in a biocompatible formulation is a sought-after goal in modern pharmaceutical technology. Zein is a hydrophobic protein which has several advantageous properties that make it suitable for use as a biocompatible and degradable material under physiological conditions. It is, therefore, proposed for different biomedical and pharmaceutical applications. In particular, due to its gelling properties, it can be used to form a polymeric network able to preserve biomolecules from harsh environments. The current study was designed to investigate the influence of different probes on the rheological properties of gels made up of zein, in order to characterize the systems as a function of the polymer concentration. Four model compounds characterized by different physico-chemical properties were entrapped in zein gels, and different behaviors (viscoelastic or pronounced solid-like characteristics) of the systems were observed. Zein-based gels showed various release profiles of the encapsulated compounds, suggesting that there are different interaction rates between the probes and the polymeric matrix.

The Rheolaser Master™ and Kinexus Rotational Rheometer® to Evaluate the Influence of Topical Drug Delivery Systems on Rheological Features of Topical Poloxamer Gel.

Poloxamer 407 copolymer is a versatile and widely used thermo-reversible material. Its use has many advantages, such as bio-adhesion, enhanced solubilization of poorly water-soluble drugs and many applications fields like oral, rectal, topical, nasal drug administration. Hydrogels made up of Poloxamer 407 are characterized by specific rheological features, which are affected by temperature, concentration and presence of other compounds. A strategic approach in topical therapeutic treatments may be the inclusion of drug delivery systems, such as ethosomes, transfersomes and niosomes, into hydrogel poloxamer formulation. The evaluation of the interaction between colloidal carriers and the Poloxamer 407 hydrogel network is essential for a suitable design of an innovative topical dosage form. For this reason, the Rheolaser Master™, based on diffusing wave spectroscopy, and a Kinexus Rotational Rheometer were used to evaluate the influence of nanocarriers on the microrheological features of hydrogels. The advantages of the Rheolaser Master™ analyzer are: (i) its ability to determine viscoelastic parameter, without altering or destroying the sample and at rest (zero shear); (ii) possibility of aging analysis on the same sample. This study provide evidence that vesicular systems do not influence the rheological features of the gel, supporting the possibility to encapsulate an innovative system into a three-dimensional network.

Liquid crystal delivery of ciprofloxacin to treat infections of the female reproductive tract.

Infections of the female reproductive tract are a major cause of morbidity and mortality in humans, requiring significant investment to sustain treatment and representing a major challenge to health. The increasing prevalence of bacterial resistance, and an almost complete absence of new antibiotic therapies for the past five decades, mean there is a desperate need for novel approaches to the treatment of bacterial infections. Within the present study, we demonstrate the effective ex vivo treatment of bacterial infection of the female reproductive tract using a controlled-release, liquid crystal-based platform. Liquid crystal encapsulation of ciprofloxacin significantly enhanced its bactericidal efficacy and reduced cell toxicity. Liquid crystal structures are low-cost, simple to manufacture and provide a sustained-release profile of encapsulated ciprofloxacin. Treatment of Escherichia coli infected reproductive tract epithelial cells and whole organ cultures with liquid crystal encapsulated ciprofloxacin proved to be an effective strategy for reducing bacterial load and reproductive tract inflammatory responses to infection. These data suggest that such an approach could provide an efficacious treatment modality for enhancing the effectiveness of current antibiotic therapies.

pH-sensitive niosomes: Effects on cytotoxicity and on inflammation and pain in murine models.

pH-sensitive nonionic surfactant vesicles (niosomes) by polysorbate-20 (Tween-20) or polysorbate-20 derivatized by glycine (added as pH sensitive agent), were developed to deliver Ibuprofen (IBU) and Lidocaine (LID). For the physical-chemical characterization of vesicles (mean size, size distribution, zeta potential, vesicle morphology, bilayer properties and stability) dynamic light scattering (DLS), small angle X-ray scattering and fluorescence studies were performed. Potential cytotoxicity was evaluated on immortalized human keratinocyte cells (HaCaT) and on immortalized mouse fibroblasts Balb/3T3. In vivo antinociceptive activity (formalin test) and anti-inflammatory activity tests (paw edema induced by zymosan) in murine models were performed on drug-loaded niosomes. pH-sensitive niosomes were stable in the presence of 0 and 10% fetal bovine serum, non-cytotoxic and able to modify IBU or LID pharmacological activity in vivo. The synthesis of stimuli responsive surfactant, as an alternative to add pH-sensitive molecules to niosomes, could represent a promising delivery strategy for anesthetic and anti-inflammatory drugs.

Niosomes as Drug Nanovectors: Multiscale pH-Dependent Structural Response.

The use of nanocarriers, which respond to different stimuli controlling their physicochemical properties and biological responsivness, shows a growing interest in pharmaceutical science. The stimuli are activated by targeting tissues and biological compartments, e.g., pH modification, temperature, redox condition, enzymatic activity, or can be physically applied, e.g., a magnetic field and ultrasound. pH modification represents the easiest method of passive targeting, which is actually used to accumulate nanocarriers in cells and tissues. The aim of this paper was to physicochemically characterize pH-sensitive niosomes using different experimental conditions and demonstrate the effect of surfactant composition on the supramolecular structure of niosomes. In this attempt, niosomes, made from commercial (Tween21) and synthetic surfactants (Tween20 derivatives), were physicochemically characterized by using different techniques, e.g., transmission electron microscopy, Raman spectroscopy, and small-angle X-ray scattering. The changes of niosome structure at different pHs depend on surfactants, which can affect the supramolecular structure of colloidal nanocarriers and their potential use both in vitro and in vivo. At pH 7.4, the shape and structure of niosomes have been maintained; however, niosomes show some differences in terms of bilayer thicknesses, water penetration, membrane coupling, and cholesterol dispersion. The acid pH (5.5) can increase the bilayer fluidity, and affect the cholesterol depletion. In fact, Tween21 niosomes form large vesicles with lower curvature radius at acid pH; while Tween20-derivative niosomes increase the intrachain mobility within a more interchain correlated membrane. These results demonstrate that the use of multiple physicochemical procedures provides more information about supramolecular structures of niosomes and improves the opportunity to deeply investigate the effect of stimuli responsiveness on the niosome structure.

Pharmacological effect of a new idebenone formulation in a model of carrageenan-induced inflammatory pain.

Considerable evidence demonstrated that the central role of reactive oxygen species and reactive nitrogen species (ROS and RNS) in the development of thermal hyperalgesia is associated to acute and chronic inflammation. Idebenone (IDE), a synthetic analogue of the endogenous cellular antioxidant coenzyme Q10 (CoQ10), is an active drug in the central nervous system which shows a protection in a variety of neurological disorders. Since it is lipophilic, poorly water soluble and highly bound to plasma proteins, different technological approaches have been explored to increase its solubility and new pharmaceutical properties. Therefore, it has been complexed with HP-ß-cyclodextrins (HP) and its efficacy has been assessed in an animal model of carrageenan-induced thermal hyperalgesia. All male rats used for this study received a subplantar injection of carrageenan into the right hindpaw in the presence or absence of IDE alone and IDE/HP complex. We observed that IDE poorly reduced painful carrageenan effects whereas IDE/HP complex was able to prevent carrageenan-induced hyperalgesia and edema in a dose-dependent manner, reducing spinal MDA levels and protein nitration. Hence, our results demonstrated that when complexed with HP, idebenone exerts a potent analgesic and anti-inflammatory efficacy.

Microextraction by packed sorbent and HPLC-PDA quantification of multiple anti-inflammatory drugs and fluoroquinolones in human plasma and urine.

We developed and validated an analytical method based on microextraction packed sorbent (MEPS) and high-performance liquid chromatography (HPLC) coupled to photodiode array (PDA) detector to simultaneously quantify multiple nonsteroidal anti-inflammatory drugs (NSAIDs) and fluoroquinolones (FLQs), which may provide as combination several adverse reactions in nephrology and neurology. The linearity range from LOQs (0.1 µg/mL) to 10 µg/mL, and LODs values were 0.03 µg/mL for both NSAIDs and FLQs. The validation was performed according to international guidelines and the accuracy was tested measuring the precision, intermediate precision and trueness. The drugs stability was tested under different storage conditions (+4 °C and -20 °C) and after three different cycles of freezing and thawing. The method can be a suitable tool to simultaneously detect a possible association of drugs in human biological samples and provide several potentialities for clinical applications, bioequivalence studies, pharmacodynamics and toxicodynamics of different pharmaceutical dosage forms showing NSAIDs and FLQs.

Polyaspartamide-doxorubicin conjugate as potential prodrug for anticancer therapy.

PURPOSE: To synthesize a new polymeric prodrug based on α,ß-poly(N-2-hydroxyethyl)(2-aminoethylcarbamate)-d,l-aspartamide copolymer bearing amine groups in the side chain (PHEA-EDA), covalently linked to the anticancer drug doxorubicin and to test its potential application in anticancer therapy. METHODS: The drug was previously derivatized with a biocompatible and hydrophilic linker, leading to a doxorubicin derivative highly reactive with amino groups of PHEA-EDA. The PHEA-EDA-DOXO prodrug was characterized in terms of chemical stability. The pharmacokinetics, biodistribution and cytotoxicity of the product was investigated in vitro and in vivo on human breast cancer MCF-7 and T47D cell lines and NOD-SCID mice bearing a MCF-7 human breast carcinoma xenograft. Data collected were compared to those obtained using free doxorubicin. RESULTS: The final polymeric product is water soluble and easily hydrolysable in vivo, due to the presence of ester and amide bonds along the spacer between the drug and the polymeric backbone. In vitro tests showed a retarded cytotoxic effect on tumor cells, whereas a significant improvement of the in vivo antitumor activity of PHEA-EDA-DOXO and a survival advantage of the treated NOD-SCID mice was evidenced, compared to that of free doxorubicin. CONCLUSIONS: The features of the PHEA-EDA-DOXO provide a potential protection of the drug from the plasmatic enzymatic degradation and clearance, an improvement of the blood pharmacokinetic parameters and a suitable body biodistribution. The data collected support the promising rationale of the proposed macromolecular prodrug PHEA-EDA-DOXO for further potential development and application in the treatment of solid cancer diseases.

Evaluation of anticancer activity of celastrol liposomes in prostate cancer cells.

CONTEXT: Celastrol, a natural compound derived from the herb Tripterygium wilfordii, is known to have anticancer activity, but is not soluble in water. OBJECTIVE: Formation of celastrol liposomes, to avoid the use of toxic solubilising agents. MATERIALS AND METHODS: Two different formulations of PEGylated celastrol liposomes were fabricated. Liposomal characteristics and serum stability were determined using dynamic light scattering. Drug entrapment efficacy and drug release were measured spectrophotometrically. Cellular internalisation and anticancer activity was measured in prostate cancer cells. RESULTS: Liposomal celastrol displayed efficient serum stability, cellular internalisation and anticancer activity, comparable to that of the free drug reconstituted in dimethyl sulfoxide. DISCUSSION AND CONCLUSION: Liposomal celastrol can decrease the viability of prostate cancer cells, while eliminating the need for toxic solubilising agents.

Reflectance spectroscopy: a non-invasive strategy to explore skin reactions to topical products.

Reflectance spectroscopy has emerged as a powerful analytical technique in the field of dermatology, offering a non-invasive strategy to assess several cutaneous properties and skin response to topical products. By analyzing reflected light across different wavelengths, reflectance spectroscopy allows the quantification of cutaneous parameters, such as erythema index and melanin content. Moreover, this analytical technique enables the monitoring of any changes in skin physiology facilitating the assessment of long-term effects of topical products as well as predicting cutaneous diseases. This review provides an overview of the application of reflectance spectroscopy in investigating skin properties and reaction to topical applied products, including both pharmaceutical and cosmetic formulations, thereby aiding in the development of personalized solutions tailored to individual needs.

OX26-cojugated gangliosilated liposomes to improve the post-ischemic therapeutic effect of CDP-choline.

Cerebrovascular impairment represents one of the main causes of death worldwide with a mortality rate of 5.5 million per year. The disability of 50% of surviving patients has high social impacts and costs in long period treatment for national healthcare systems. For these reasons, the efficacious clinical treatment of patients, with brain ischemic stroke, remains a medical need. To this aim, a liposome nanomedicine, with monosialic ganglioside type 1 (GM1), OX26 (an anti-transferrin receptor antibody), and CDP-choline (a neurotrophic drug) (CDP-choline/OX26Lip) was prepared. CDP-choline/OX26Lip were prepared by a freeze and thaw method and then extruded through polycarbonate filters, to have narrow size distributed liposomes of ~80 nm. CDP-choline/OX26Lip were stable in human serum, they had suitable pharmacokinetic properties, and 30.0 ± 4.2% of the injected drug was still present in the blood stream 12 h after its systemic injection. The post-ischemic therapeutic effect of CDP-choline/OX26Lip is higher than CDP-choline/Lip, thus showing a significantly high survival rate of the re-perfused post-ischemic rats, i.e. 96% and 78% after 8 days. The treatment with CDP-choline/OX26Lip significantly decreased the peroxidation rate of ~5-times compared to CDP-choline/Lip; and the resulting conjugated dienes, that was 13.9 ± 1.1 mmol/mg proteins for CDP-choline/Lip and 3.1 ± 0.8 for CDP-choline/OX26Lip. OX26 increased the accumulation of GM1-liposomes in the brain tissues and thus the efficacious of CDP-choline. Therefore, this nanomedicine may represent a strategy for the reassessment of CDP-choline to treat post-ischemic events caused by brain stroke, and respond to a significant clinical need.

Improved anti-breast cancer activity by doxorubicin-loaded super stealth liposomes.

PEGylation is currently used for the synthesis of stealth liposomes and to enhance the pharmacokinetic and biopharmaceutical properties of payloads. PEGylated dendron phospholipids can decrease the detachment of polyethylene glycol (PEG) from the liposomal surface owing to an increased hydrophobic anchoring effect on the phospholipid bilayer of liposomes and thus generating super stealth liposomes that are suitable for the systemic delivery of anticancer drugs. Herein, doxorubicin hydrochloride-loaded super stealth liposomes were studied for the treatment of breast cancer lung metastasis in an animal model. The results demonstrated that the super stealth liposomes had suitable physicochemical properties for in vivo administration and could significantly increase the efficacy of doxorubicin in breast cancer lung metastasis tumor-bearing mice compared to the free drug. The super stealth liposomes also increased doxorubicin accumulation inside the tumor tissue. The permanence of PEG on the surface of the super stealth liposomes favored the formation of a depot of therapeutic nanocarriers inside the tumor tissue by improving their permanence after stopping treatment. The doxorubicin-loaded super stealth liposomes increased the survival of the mouse tumor model. These promising results demonstrate that the doxorubicin-loaded super stealth liposomes could be an effective nanomedicine to treat metastatic breast cancer.