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.

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.

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.

Acronychiabaueri Analogue Derivative-Loaded Ultradeformable Vesicles: Physicochemical Characterization and Potential Applications.

Elastic and ultradeformable liposomes were synthesized and physicochemically characterized to make suitable topical formulations for delivering the anti-inflammatory and anticancer compound 3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans-propenoic acid. The average sizes of elastic and ultradeformable liposomes are below 300 nm, while the size distribution and Z-potential are below 0.3 and - 25 mV, respectively. The presence of 3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans-propenoic acid does not affect the physicochemical parameters of nanovesicles. Elastic and ultradeformable liposomes show a zero order release kinetic and are stable at room temperature for a long time with or without 3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans-propenoic acid. The ultradeformable liposomes are more deformable than elastic liposomes. These differences may depend on sodium cholate derivatives making nanoformulations. The 3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans-propenoic acid-loaded elastic and ultradeformable liposomes can provide innovative nanotherapeutics-based natural compounds for the potential treatment of cutanous inflammation.

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.

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.

Skin Tolerability of Oleic Acid Based Nanovesicles Designed for the Improvement of Icariin and Naproxen Percutaneous Permeation.

Deformable nanovesicles have a crucial role in topical drug delivery through the skin, due to their capability to pass intact the stratum corneum and epidermis (SCE) and significantly increase the efficacy and accumulation of payloads in the deeper layers of the skin. Namely, lipid-based ultradeformable nanovesicles are versatile and load bioactive molecules with different physicochemical properties. For this reason, this study aims to make oleic acid based nanovesicles (oleosomes) for the codelivery of icariin and sodium naproxen and increase their permeation through the skin. Oleosomes have suitable physicochemical properties and long-term stability for a potential dermal or transdermal application. The inclusion of oleic acid in the lipid bilayer increases 3-fold the deformable properties of oleosomes compared to conventional liposomes and significantly improves the percutaneous permeation of icariin and sodium naproxen through the human SCE membranes compared to hydroalcoholic solutions of both drugs. The tolerability studies on human volunteers demonstrate that oleosomes are safer and speed up the recovery of transepidermal water loss (TEWL) baselines compared to saline solution. These results highlight promising properties of icariin/sodium naproxen coloaded oleosomes for the treatment of skin disorders and suggest the potential future applications of these nanovesicles for further in vivo experiments.

Perspective use of bio-adhesive liquid crystals as ophthalmic drug delivery systems.

The success of many drugs in ophthalmic treatments is hindered by their physico-chemical properties and the limited precorneal retention time. Here, lyotropic liquid crystals are proposed as a new ophthalmic drug delivery system. Acyclovir was chosen as model drug for its solubility and its controlled release from cubic phase was achieved. We demonstrated the effortless application of lamellar phase on corneal surface and its ability to convert itself in cubic phase in situ. While the complex viscosity of lamellar phase was affected by temperature (5.1 ± 1.4 kPa·s at 25 °C and 0.12 ± 0.001 Pa·s at 35 °C, respectively), the cubic phase shown no changes in viscosity values and shear thinning behaviour at both temperatures and even in presence of the drug The degradation kinetic of drug-loaded cubic phase was slightly slower than the empty formulation, recording 27.92 ± 1.43% and 33.30 ± 3.11% of weight loss after 8 h. Ex vivo studies conducted on porcine eyeballs and isolated cornea confirmed the instantaneous transition to cubic phase, its ability to resist to gravity force, and forced dripping of simulated tear fluid. Histopathological investigation showed how treated cornea did not report changes in epithelial and stroma structures. In summary, lyotropic liquid crystals could represent an advantageous ophthalmic drug delivery system.

Gelled Liquid Crystal Nanocarriers for Improved Antioxidant Activity of Resveratrol.

As many natural origin antioxidants, resveratrol is characterized by non-suitable physicochemical properties for its topical application. To allow its benefits to manifest on human skin, resveratrol has been entrapped within liquid crystal nanocarriers (LCNs) made up of glyceryl monooleate, a penetration enhancer, and DSPE-PEG 750. The nanosystems have been more deeply characterized by using dynamic light scattering and Turbiscan Lab® Expert optical analyzer, and they have been tested in vitro on NCTC 2544. The improved antioxidant activity of entrapped resveratrol was evaluated on keratinocyte cells as a function of its concentration. Finally, to really propose the resveratrol-loaded LCNs for topical use, the systems were gelled by using two different gelling agents, poloxamer P407 and carboxymethyl cellulose, to improve the contact time between skin and formulation. The rheological features of obtained gels were evaluated using two important methods (microrheology at rest and dynamic rheology), before testing their safety profile on human healthy volunteers. The obtained results showed the ability of LCNs to improve antioxidant activity of RSV and the gelled LCNs showed good rheological profiles. In conclusion, the results confirmed the potentiality of gelled resveratrol-loaded nanosystems for skin disease, mainly related to their antioxidant effects.

Solid Lipid Nanoparticles Containing Morin: Preparation, Characterization, and Ex Vivo Permeation Studies.

In recent years, bioactive compounds have been the focus of much interest in scientific research, due to their low toxicity and extraordinary properties. However, they possess poor solubility, low chemical stability, and unsustainable bioavailability. New drug delivery systems, and among them solid lipid nanoparticles (SLNs), could minimize these drawbacks. In this work, morin (MRN)-loaded SLNs (MRN-SLNs) were prepared using a solvent emulsification/diffusion method, using two different lipids, Compritol® 888 ATO (COM) or Phospholipon® 80H (PHO). SLNs were investigated for their physical-chemical, morphological, and technological (encapsulation parameters and in vitro release) properties. We obtained spherical and non-aggregated nanoparticles with hydrodynamic radii ranging from 60 to 70 nm and negative zeta potentials (about -30 mV and -22 mV for MRN-SLNs-COM and MRN-SLNs-PHO, respectively). The interaction of MRN with the lipids was demonstrated via µ-Raman spectroscopy, X-ray diffraction, and DSC analysis. High encapsulation efficiency was obtained for all formulations (about 99%, w/w), particularly for the SLNs prepared starting from a 10% (w/w) theoretical MRN amount. In vitro release studies showed that about 60% of MRN was released within 24 h and there was a subsequent sustained release within 10 days. Finally, ex vivo permeation studies with excised bovine nasal mucosa demonstrated the ability of SLNs to act as a penetration enhancer for MRN due to the intimate contact and interaction of the carrier with the mucosa.

Alginate-Based Composites for Corneal Regeneration: The Optimization of a Biomaterial to Overcome Its Limits.

For many years, corneal transplantation has been the first-choice treatment for irreversible damage affecting the anterior part of the eye. However, the low number of cornea donors and cases of graft rejection highlighted the need to replace donor corneas with new biomaterials. Tissue engineering plays a fundamental role in achieving this goal through challenging research into a construct that must reflect all the properties of the cornea that are essential to ensure correct vision. In this review, the anatomy and physiology of the cornea are described to point out the main roles of the corneal layers to be compensated and all the requirements expected from the material to be manufactured. Then, a deep investigation of alginate as a suitable alternative to donor tissue was conducted. Thanks to its adaptability, transparency and low immunogenicity, alginate has emerged as a promising candidate for the realization of bioengineered materials for corneal regeneration. Chemical modifications and the blending of alginate with other functional compounds allow the control of its mechanical, degradation and cell-proliferation features, enabling it to go beyond its limits, improving its functionality in the field of corneal tissue engineering and regenerative medicine.

Macrophage-Derived Extracellular Vesicles: A Promising Tool for Personalized Cancer Therapy.

The incidence of cancer is increasing dramatically, affecting all ages of the population and reaching an ever higher worldwide mortality rate. The lack of therapies' efficacy is due to several factors such as a delay in diagnosis, tumor regrowth after surgical resection and the occurrence of multidrug resistance (MDR). Tumor-associated immune cells and the tumor microenvironment (TME) deeply affect the tumor's progression, leading to several physicochemical changes compared to physiological conditions. In this scenario, macrophages play a crucial role, participating both in tumor suppression or progression based on the polarization of onco-suppressive M1 or pro-oncogenic M2 phenotypes. Moreover, much evidence supports the pivotal role of macrophage-derived extracellular vesicles (EVs) as mediators in TME, because of their ability to shuttle the cell-cell and organ-cell communications, by delivering nucleic acids and proteins. EVs are lipid-based nanosystems with a broad size range distribution, which reflect a similar composition of native parent cells, thus providing a natural selectivity towards target sites. In this review, we discuss the impact of macrophage-derived EVs in the cancer's fate as well as their potential implications for the development of personalized anticancer nanomedicine.

Ammonium Glycyrrhizinate and Bergamot Essential Oil Co-Loaded Ultradeformable Nanocarriers: An Effective Natural Nanomedicine for In Vivo Anti-Inflammatory Topical Therapies.

Bergamot essential oil (BEO) and Ammonium glycyrrhizinate (AG), naturally derived compounds, have remarkable anti-inflammatory properties, thus making them suitable candidates for the treatment of skin disorders. Despite this, their inadequate physicochemical properties strongly compromise their topical application. Ultradeformable nanocarriers containing both BEO and AG were used to allow their passage through the skin, thus maximizing their therapeutic activity. Physicochemical characterization studies were performed using Zetasizer Nano ZS and Turbiscan Lab®. The dialysis method was used to investigate the release profile of the active compounds. In vivo studies were performed on human healthy volunteers through the X-Rite spectrophotometer. The nanosystems showed suitable features for topical cutaneous administration in terms of mean size, surface charge, size distribution, and long-term stability/storability. The co-delivery of BEO and AG in the deformable systems improved both the release profile kinetic of ammonium glycyrrhizinate and deformability properties of the resulting nanosystems. The topical cutaneous administration on human volunteers confirmed the efficacy of the nanosystems. In detail, BEO and AG-co-loaded ultradeformable vesicles showed a superior activity compared to that recorded from the ones containing AG as a single agent. These results are promising and strongly encourage a potential topical application of AG/BEO co-loaded nanocarriers for anti-inflammatory therapies.

Multidrug Idebenone/Naproxen Co-loaded Aspasomes for Significant in†vivo Anti-inflammatory Activity.

The use of proper nanocarriers for dermal and transdermal delivery of anti-inflammatory drugs recently gained several attentions in the scientific community because they pass intact and accumulate payloads in the deepest layers of skin tissue. Ascorbyl palmitate-based vesicles (aspasomes) can be considered a promising nanocarrier for dermal and transdermal delivery due to their skin whitening properties and suitable delivery of payloads through the skin. The aim of this study was the synthesis of multidrug Idebenone/naproxen co-loaded aspasomes for the development of an effective anti-inflammatory nanomedicine. Aspasomes had suitable physicochemical properties and were safe in vivo if topically applied on human healthy volunteers. Idebenone/naproxen co-loaded aspasomes demonstrated an increased therapeutic efficacy of payloads compared to the commercially available Naprosyn® gel, with a rapid decrease of chemical-induced erythema on human volunteers. These promising results strongly suggested a potential application of Idebenone/naproxen multidrug aspasomes for the development of an effective skin anti-inflammatory therapy.

Lyotropic Liquid Crystals: A Biocompatible and Safe Material for Local Cardiac Application.

The regeneration of cardiac tissue is a multidisciplinary research field aiming to improve the health condition of the post-heart attack patient. Indeed, myocardial tissue has a poor ability to self-regenerate after severe damage. The scientific efforts focused on the research of a biomaterial able to adapt to heart tissue, thus guaranteeing the in situ release of active substances or growth promoters. Many types of hydrogels were proposed for this purpose, showing several limitations. The aim of this study was to suggest a new usage for glyceryl monooleate-based lyotropic liquid crystals (LLCs) as a biocompatible and inert material for a myocardial application. The main advantages of LLCs are mainly related to their easy in situ injection as lamellar phase and their instant in situ transition in the cubic phase. In vivo studies proved the biocompatibility and the inertia of LLCs after their application on the myocardial tissue of mice. In detail, the cardiac activity was monitored through 28 days, and no significant alterations were recorded in the heart anatomy and functionality. Moreover, gross anatomy showed the ability of LLCs to be bio-degraded in a suitable time frame. Overall, these results permitted us to suppose a potential use of LLCs as materials for cardiac drug delivery.

Injectable Drug Delivery Systems for Osteoarthritis and Rheumatoid Arthritis.

Joint diseases are one of the most common causes of morbidity and disability worldwide. The main diseases that affect joint cartilage are osteoarthritis and rheumatoid arthritis, which require chronic treatment focused on symptomatic relief. Conventional drugs administered through systemic or intra-articular routes have low accumulation and/or retention in articular cartilage, causing dose-limiting toxicities and reduced efficacy. Therefore, there is an urgent need to develop improved strategies for drug delivery, in particular, the use of micro- and nanotechnology-based methods. Encapsulation of therapeutic agents in delivery systems reduces drug efflux from the joint and protects against rapid cellular and enzymatic clearance following intra-articular injection. Consequently, the use of drug delivery systems decreases side effects and increases therapeutic efficacy due to enhanced drug retention in the intra-articular space. Additionally, the frequency of intra-articular administration is reduced, as delivery systems enable sustained drug release. This review summarizes various advanced drug delivery systems, such as nano- and microcarriers, developed for articular cartilage diseases.