Search

Nowadays, packaging technologies have been extensively developed, including active and intelligent packages able to promote quality, safety, and the product shelf life. At this purpose, the aim of the study was focused on the design and development of polyvinyl alcohol-based nanofibers doped with two natural clays, montmorillonite or clinoptilolite, and loaded with chlorogenic acid, as nanofibrous membranes to control microbial contamination and oxidative state upon direct contact. The results showed that the 1 % w/w clay doping was the optimal concentration to obtain continuous and uniform nanofibers. In addition, chlorogenic acid loading (5 % w/w) into the nanofibers did not change the systems morphology, resulting in a chlorogenic acid sustained release, achieving 100 % within 24 h for all the systems with enhanced antioxidant and antimicrobial activities. Depending on their structure, the presence of the clays mineral was able to affect the aqueous vapor permeability. These results suggested the promising applications of the clay doped polyvinyl alcohol-based nanofibrous membranes as smart advanced material able to control microbial contamination and oxidative degradation to be used in biomedical field or as active packaging.

Most of the therapeutic systems developed for managing chronic skin wounds lack adequate mechanical and hydration properties, primarily because they rely on a single component. This study addresses this issue by combining organic and inorganic materials to obtain hybrid films with enhanced mechanical behavior, adhesion, and fluid absorption properties. To that aim, chitosan/hydrolyzed collagen blends were mixed with halloysite/antimicrobial nanohybrids at 10% and 20% (w/w) using glycerin or glycerin/polyethylene glycol-1500 as plasticizers. The films were characterized through the use of Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), and electron microscopy. The mechanical properties were evaluated macroscopically using tensile tests, and at a nanoscale through atomic force microscopy (AFM) and nanoindentation. Thermodynamic studies were conducted to assess their hydrophilic or hydrophobic character. Additionally, in vitro cytocompatibility tests were performed on human keratinocytes. Results from FTIR, TGA, AFM and electron microscopy confirmed the hybrid nature of the films. Both tensile tests and nanomechanical measurements postulated that the nanohybrids improved the films’ toughness and adhesion and optimized the nanoindentation properties. All nanohybrid-loaded films were hydrophilic and non-cytotoxic, showcasing their potential for skin wound applications given their enhanced performance at the macro- and nanoscale.

The high rate of rejection and failure of orthopedic implants is primarily attributed to incomplete osseointegration and stress at the implant-to-bone interface due to significant differences in the mechanical properties of the implant and the surrounding bone. Various surface treatments have been developed to enhance the osteoconductive properties of implants. The aim of this work was the in vitro characterization of titanium alloy modified with a nanocrystalline hydroxyapatite surface layer in relative comparison to unmodified controls. This investigation focused on the behavior of the surface treatment in relation to the physiological environment. Moreover, the osteogenic response of human osteoblasts and adipose stem cells was assessed. Qualitative characterization of cellular interaction was performed via confocal laser scanning microscopy focusing on the cell nuclei and cytoskeletons. Filipodia were assessed using scanning electron microscopy. The results highlight that the HA treatment promotes protein adhesion as well as gene expression of osteoblasts and stem cells, which is relevant for the inorganic and organic components of the extracellular matrix and bone. In particular, cells grown onto HA-modified titanium alloy are able to promote ECM production, leading to a high expression of collagen I and non-collagenous proteins, which are crucial for regulating mineral matrix formation. Moreover, they present an impressive amount of filipodia having long extensions all over the test surface. These findings suggest that the HA surface treatment under investigation effectively enhances the osteoconductive properties of Ti6Al4V ELI.

To date, the need for biomaterials capable of improving the treatment of chronic skin wounds remains a clinical challenge. The aim of the present work is to formulate and characterize chitosan (Cs)/hydrolyzed collagen (HC) films as potential biomaterials with improved mechanical and hydration performances compared to single component formulations. Films were made by the solvent casting method, with or without glycerin and/or PEG1500 as plasticizers, resulting in a total of eight formulations. All films were characterized by their physico-chemical characteristics and their mechanical and hydration features. A full factorial design was also used to statistically assess the effect of HC concentration, type and concentration of plasticizers and their possible interactions on mechanical and swelling behaviors. Solid state characterization confirmed the hybrid nature of the films, with suggested electrostatic interactions between Cs and HC. Mechanical and swelling properties, along with the analysis of the experimental design, allowed the identification of formulations containing high HC concentration (2% w/v) and glycerin or glycerin/PEG1500 as more suitable candidates for skin wound treatment. Finally, viability assay of immortalized human keratinocytes (HaCaT) showed no statistical differences in cell survival compared to the complete culture medium, suggesting their potential as a promising tool for biomedical applications.

Introduction: Recently, mycelia of Ganoderma lucidum and Pleurotus ostreatus, edible fungi, have been characterized in vitro as self-growing biomaterials for tissue engineering since they are constituted of interconnected fibrous networks resembling the dermal collagen structure.Aim: This work aims to investigate the biopharmaceutical properties of G. lucidum and P. ostreatus mycelia to prove their safety and effectiveness in tissue engineering as dermal substitutes.Methods: The mycelial materials were characterized using a multidisciplinary approach, including physicochemical properties (morphology, thermal behavior, surface charge, and isoelectric point). Moreover, preclinical properties such as gene expression and in vitro wound healing assay have been evaluated using fibroblasts. Finally, these naturally-grown substrates were applied in vivo using a murine burn/excisional wound model.Conclusions: Both G. lucidum and P. ostreatus mycelia are biocompatible and able to safely and effectively enhance tissue repair in vivo in our preclinical model.

Eutectogels (Egels) are an emerging class of soft ionic materials outperforming traditional temperature-intolerant hydrogels and costly ionogels. Due to their excellent elasticity, non-volatile nature, and adhesion properties, Egels are attracting a great deal of interest in the biomedical space. Herein, we report the first example of adhesive Egels loading drug nanocrystals (Egel-NCs) for controlled delivery to mucosal tissues. These soft materials were prepared using gelatin, glycerine, a deep eutectic solvent (DES) based on choline hydrochloride and glycerol, and nanocrystallised curcumin, a model drug with potent antimicrobial and anti-inflammatory activities. We first explored the impact of the biopolymer concentration on the viscoelastic and mechanical properties of the networks. Thanks to the dynamic interactions between gelatin and the DES, the Egel showed excellent stretchability and elasticity (up to ≈160%), reversible gel-sol phase transition at mild temperature (≈50 ​°C), 3D-printing ability, and good adhesion to mucin protein (stickiness ≈40 ​kPa). In vitro release profiles demonstrated the ability of the NCs-based Egel to deliver curcumin for up to four weeks and deposit significantly higher drug amounts in excised porcine mucosa compared to the control cohort. All in all, this study opens new prospects in designing soft adhesive materials for long-acting drug delivery and paves the way to explore novel eutectic systems with multiple therapeutic applications.

Chronic wounds (resulting from underlying disease, metabolic disorders, infections, trauma, and even tumours) pose significant health problems. In this work, microparticles, based on polysaccharides (maltodextrin or dextran) and amino acids, and doped with antibacterial nanoparticles (CuO or ZnO NPs) are designed. Smart nano-in-microparticles with a hierarchical 3D structure are developed. The ultimate goal aims at an innovative platform to achieve skin repair and to manage skin colonization by avoiding infection that could delay and even impair the healing process. The microparticles are prepared by spray-drying and cross-linked by heating, to obtain insoluble scaffolds able to facilitate cell proliferation in the wound bed. The nano-in-microparticles are characterized using a multidisciplinary approach: chemico–physical properties (SEM, SEM-EDX, size distribution, swelling and degradation properties, structural characterization - FTIR, XRPD, SAXS – mechanical properties, surface zeta potential) and preclinical properties (in vitro biocompatibility and whole-blood clotting properties, release studies and antimicrobial properties, and in vivo safety and efficacy on murine burn/excisional wound model) were assessed. The hierarchical 3D nano-in microparticles demonstrate to promote skin tissue repair in a preclinical study, indicating that this platform deserves particular attention and further investigation will promote the prototypes translation to clinics.

Acheta domesticus (house cricket) has been recently introduced into the official European list of novel foods, representing an alternative and sustainable food source. Up to now, the chemical characterization of this edible insect has been focused only on specific classes of compounds. Here, three production batches of an A. domesticus powder were investigated by means of a multimethodological approach based on NMR, FT-ICR MS, and GC-MS methodologies. The applied analytical protocol, proposed for the first time in the study of an edible insect, allowed us to identify and quantify compounds not previously reported in crickets. In particular, methyl-branched hydrocarbons, previously identified in other insects, together with other compounds such as citrulline, formate, γ-terpinene, p-cymene, α-thujene, β-thujene, and 4-carene were detected. Amino acids, organic acids, and fatty acids were also identified and quantified. The improved knowledge of the chemical profile of this novel food opens new horizons both for the use of crickets as a food ingredient and for the use of extracts for the production of new formulations. In order to achieve this objective, studies regarding safety, biological activity, bioaccessibility, and bioavailability are needed as future perspectives in this field.

Several nanomedicine based medicinal products recently reached the market thanks to the drive of the COVID-19 pandemic. These products are characterized by criticality in scalability and reproducibility of the batches, and the manufacturing processes are now being pushed towards continuous production to face these challenges. Although the pharmaceutical industry, because of its deep regulation, is characterized by slow adoption of new technologies, recently, the European Medicines Agency (EMA) took the lead in pushing for process improvements using technologies already established in other manufacturing sectors. Foremost among these technologies, robotics is a technological driver, and its implementation in the pharma field should cause a big change, probably within the next 5 years. This paper aims at describing the regulation changes mainly in aseptic manufacturing and the use of robotics in the pharmaceutical environment to fulfill GMP (good manufacturing practice). Special attention is therefore paid at first to the regulatory aspect, explaining the reasons behind the current changes, and then to the use of robotics that will characterize the future of manufacturing especially in aseptic environments, moving from a clear overview of robotics to the use of automated systems to design more efficient processes, with reduced risk of contamination. This review should clarify the regulation and technological scenario and provide pharmaceutical technologists with basic knowledge in robotics and automation, as well as engineers with regulatory knowledge to define a common background and language, and enable the cultural shift of the pharmaceutical industry.

Clay minerals are historically among the most used materials with a wide variety of applications. In pharmaceutical and biomedical fields, their healing properties have always been known and used in pelotherapy and therefore attractive for their potential. In recent decades, the research has therefore focused on the systematic investigation of these properties. This review aims to describe the most relevant and recent uses of clays in the pharmaceutical and biomedical field, especially for drug delivery and tissue engineering purposes. Clay minerals, which are biocompatible and non-toxic materials, can act as carriers for active ingredients while controlling their release and increasing their bioavailability. Moreover, the combination of clays and polymers is useful as it can improve the mechanical and thermal properties of polymers, as well as induce cell adhesion and proliferation. Different types of clays, both of natural (such as montmorillonite and halloysite) and synthetic origin (layered double hydroxides and zeolites), were considered in order to compare them and to assess their advantages and different uses.

The healing process of chronic wounds continues to be a current clinical challenge, worsened by the risk of microbial infections and bacterial resistance to the most frequent antibiotics. In this work, non-antibiotic nanohybrids based on chlorhexidine dihydrochloride and clay minerals have been developed in order to design advanced therapeutic systems aimed to enhance wound healing in chronic lesions. To prepare the nanohybrids, two methodologies have been compared: the intercalation solution procedure and the spray-drying technique, the latter as a one-step process able to reduce preparation times. Nanohybrids were then fully studied by solid state characterization techniques. Computational calculations were also performed to assess the interactions between the drug and the clays at the molecular level. In vitro human fibroblast biocompatibility and antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa were assessed to check biocompatibility and potential microbicidal effects of the obtained nanomaterials. The results demonstrated the effective organic/inorganic character of the nanohybrids with homogeneous drug distribution into the clayey structures, which had been confirmed by classical mechanics calculations. Good biocompatibility and microbicidal effects were also observed, especially for the spray-dried nanohybrids. It was suggested that it could be due to a greater contact area with target cells and bacterial suspensions.

Bentonite or palygorskite-based hydrogels have recently been suggested as a strategy to increase bioavailability and control the retention and release of therapeutic candidates. In this work, clay-based hydrogels loaded with diclofenac acid nanocrystals have been successfully designed and developed. The aim was to improve diclofenac solubility, its dissolution rate and to enhance its local bioavailability after topical application. For this purpose, diclofenac acid nanocrystals were prepared by wet media milling technology and then loaded into inorganic hydrogels based on bentonite and/or palygorskite. Diclofenac acid nanocrystals were characterized by morphology, size, and zeta potential. Moreover, rheological behavior, morphology, solid state, release studies, and in vitro skin penetration/permeation of diclofenac acid nanocrystals-loaded hydrogels were performed. The hydrogels were characterized by a crystalline structure, and demonstrated that the inclusion of diclofenac in clay-based hydrogels resulted in an increased thermal stability. The presence of both palygorskite and bentonite reduced nanocrystal mobility, and consequently its release and penetration into the skin. On the other hand, bentonite- or palygorskite-based hydrogels revealed great potential as an alternative strategy to enhance topical bioavailability of DCF nanocrystals, enhancing their penetration to the deeper skin layers.

The design of nanoparticle formulations composed of biopolymers, that govern the physicochemical properties of orally delivered insulin, relies on improving insulin stability and absorption through the intestinal mucosa while protecting it from harsh conditions in the gastrointestinal (GI) tract. Chitosan/polyethylene glycol (PEG) and albumin coating of alginate/dextran sulfate hydrogel cores are presented as a multilayer complex protecting insulin within the nanoparticle. This study aims to optimize a nanoparticle formulation by assessing the relationship between design parameters and experimental data using response surface methodology through a 3-factor 3-level optimization Box–Behnken design. While the selected independent variables were the concentrations of PEG, chitosan and albumin, the dependent variables were particle size, polydispersity index (PDI), zeta potential, and insulin release. Experimental results showed a nanoparticle size ranging from 313 to 585 nm, with PDI from 0.17 to 0.39 and zeta potential ranging from −29 to −44 mV. Insulin bioactivity was maintained in simulated GI media with over 45% cumulative release after 180 min in a simulated intestinal medium. Based on the experimental responses and according to the criteria of desirability on the experimental region’s constraints, solutions of 0.03% PEG, 0.047% chitosan and 1.20% albumin provide an optimum nanoparticle formulation for insulin oral delivery.

Tendon disorders are common medical conditions that could lead to significant disability, pain, healthcare costs, and a loss of productivity. Traditional approaches require long periods of treatment, and they largely fail due to the tissues weakening and the postoperative alterations of the normal joint mechanics. To overcome these limitations, innovative strategies for the treatment of these injuries need to be explored. The aim of the present work was the design of nano-fibrous scaffolds based on poly(butyl cyanoacrylate) (PBCA), a well-known biodegradable and biocompatible synthetic polymer, doped with copper oxide nanoparticles and caseinphosphopeptides (CPP), able to mimic the hierarchical structure of the tendon and to improve the tissue healing potential. These were developed as implants to be sutured to reconstruct the tendons and the ligaments during surgery. PBCA was synthetized, and then electrospun to produce aligned nanofibers. The obtained scaffolds were characterized for their structure and physico-chemical and mechanical properties, highlighting that CuO and CPP loading, and the aligned conformation determined an increase in the scaffold mechanical performance. Furthermore, the scaffolds loaded with CuO showed antioxidant and anti-inflammatory properties. Moreover, human tenocytes adhesion and proliferation to the scaffolds were assessed in vitro. Finally, the antibacterial activity of the scaffolds was evaluated using Escherichia coli and Staphylococcus aureus as representative of Gram-negative and Gram-positive bacteria, respectively, demonstrating that the CuO-doped scaffolds possessed a significant antimicrobial effect against E. coli. In conclusion, scaffolds based on PBCA and doped with CuO and CPP deserve particular attention as enhancers of the tendon tissue regeneration and able to avoid bacterial adhesion. Further investigation on the scaffold efficacy in vivo will assess their capability for enhancing the tendon ECM restoration in view of accelerating their translation to the clinic.

Neurological disorders affecting both CNS and PNS still represent one of the most critical and challenging pathologies, therefore many researchers have been focusing on this field in recent decades. Spinal cord injury (SCI) and peripheral nerve injury (PNI) are severely disabling diseases leading to dramatic and, in most cases, irreversible sensory, motor, and autonomic impairments. The challenging pathophysiologic consequences involved in SCI and PNI are demanding the development of more effective therapeutic strategies since, as yet, a therapeutic strategy that can effectively lead to a complete recovery from such pathologies is not available. Drug delivery systems (DDSs) based on polysaccharides have been receiving more and more attention for a wide range of applications, due to their outstanding physical-chemical properties. This review aims at providing an overview of the most studied polysaccharides used for the development of DDSs intended for the repair and regeneration of a damaged nervous system, with particular attention to spinal cord and peripheral nerve injury treatments. In particular, DDSs based on chitosan and their association with alginate, dextran, agarose, cellulose, and gellan were thoroughly revised.

Insects, especially crickets, have been proposed as a novel source of nutrients in human nutrition since they possess bioactive molecules, including high protein content, lipids, chitin, vitamins and minerals. In this work, the nutritional and functional properties of a novel Italian spray-dried (SD) cricket powder were evaluated. The powder was characterized by physico–chemical properties (morphology, size distribution, solid state, thermal profiles, and surface zeta potential), and antioxidant properties. Moreover, preclinical properties (cytocompatibility and pro-inflammatory immune response) were assessed. The powder was characterized by microparticle structure with bulges and rough surfaces, showing distinctive antioxidant properties. The preclinical results suggested that the SD crickets were biocompatible towards Caco-2 and macrophages without immune response, representing an interesting material for the food industry that could provide health benefits in addition to the basic nutritional value of traditional foods.

The poor water solubility of a significant number of active pharmaceutical ingredients (API) remains one of the main challenges in the drug development process, causing low bioavailability and therapeutic failure of drug candidates. Curcumin is a well-known Biopharmaceutics Classification System (BCS) class IV drug, characterized by lipophilicity and low permeability, which hampers topical bioavailability. Given these premises, the aim of this work was the design and the development of curcumin nanocrystals and their incorporation into natural inorganic hydrogels for topical application. Curcumin nanocrystals were manufactured by the wet ball milling technique and then loaded in clay-based hydrogels. Bentonite and/or palygorskite were selected as the inorganic gelling agents. Curcumin nanocrystal-loaded hydrogels were manufactured by means of a homogenization process and characterized with respect to their chemico-physical properties, in vitro release, antioxidant activity and skin permeation. The results highlighted that the presence of bentonite provided an increase of curcumin skin penetration and simultaneously allowed its radical scavenging properties, due to the desirable rheological characteristics, which should guarantee the necessary contact time of the gel with the skin.

The enthesis is an extremely specific region, localized at the tendon–bone interface (TBI) and made of a hybrid connection of fibrocartilage with minerals. The direct type of enthesis tissue is commonly subjected to full laceration, due to the stiffness gradient between the soft tissues and hard bone, and this often reoccurs after surgical reconstruction. For this purpose, the present work aimed to design and develop a tubular scaffold based on pullulan (PU) and chitosan (CH) and intended to enhance enthesis repair. The scaffold was designed with a topographical gradient of nanofibers, from random to aligned, and hydroxyapatite (HAP) nanoparticles along the tubular length. In particular, one part of the tubular scaffold was characterized by a structure similar to bone hard tissue, with a random mineralized fiber arrangement; while the other part was characterized by aligned fibers, without HAP doping. The tubular shape of the scaffold was also designed to be extemporarily loaded with chondroitin sulfate (CS), a glycosaminoglycan effective in wound healing, before the surgery. Micro CT analysis revealed that the scaffold was characterized by a continuous gradient, without interruptions from one end to the other. The gradient of the fiber arrangement was observed using SEM analysis, and it was still possible to observe the gradient when the scaffold had been hydrated for 6 days. In vitro studies demonstrated that human adipose stem cells (hASC) were able to grow and differentiate onto the scaffold, expressing the typical ECM production for tendon in the aligned zone, or bone tissue in the random mineralized part. CS resulted in a synergistic effect, favoring cell adhesion/proliferation on the scaffold surface. These results suggest that this tubular scaffold loaded with CS could be a powerful tool to support enthesis repair upon surgery.

In recent decades, the demand for replacement of damaged or broken tissues has increased; this poses the attention on problems related to low donor availability. For this reason, researchers focused their attention on the field of tissue engineering, which allows the development of scaffolds able to mimic the tissues’ extracellular matrix. However, tissue replacement and regeneration are complex since scaffolds need to guarantee an adequate hierarchical structured morphology as well as adequate mechanical, chemical, and physical properties to stand the stresses and enhance the new tissue formation. For this purpose, the use of inorganic materials as fillers for the scaffolds has gained great interest in tissue engineering applications, due to their wide range of physicochemical properties as well as their capability to induce biological responses. However, some issues still need to be faced to improve their efficacy. This review focuses on the description of the most effective inorganic nanomaterials (clays, nano-based nanomaterials, metal oxides, metallic nanoparticles) used in tissue engineering and their properties. Particular attention has been devoted to their combination with scaffolds in a wide range of applications. In particular, skin, orthopaedic, and neural tissue engineering have been considered.

Nanocomposites formed by clay and lipid carriers (NLCs) show a high potential for providing controlled release and specific delivery of bioactive molecules and have recently gained attention in the pharmaceutical sector due to their ability to transport hydrophilic and hydrophobic drugs. Recent studies have recognized the biological activity of the oil of Bixa orellana L. (AO) with regards to its healing, antioxidant, antibacterial, and anti-leishmanial properties. Therefore, the purpose of this study is the preparation and characterization of hybrid systems based on lipid nanocarriers and laponite for the delivery of AO. NLCs were prepared by the fusion-emulsification method, using cetyl palmitate (CP) or myristyl myristate (MM), AO, and Poloxamer 188. The morphology, hydrodynamic diameters, zeta potential (ZP), polydispersity index (PDI), thermal analysis, X-ray diffraction analysis (XRD), viscosity behavior, and cytotoxicity testing of the hybrid systems were performed. The thermal study and X-ray diffraction analyses (XRD) revealed polymorphic structural changes compatible with the amorphization of the material. Rheological assays highlighted a typical pseudoplastic behavior in all systems (MM and CP with LAP). The hybrid systems’ morphology, size diameters, and PDIs were similar, preset spherical and monodisperse structures (≈200 nm;

Nanostructured lipid carriers (NLC) have been widely studied as delivery systems for a variety of routes, including the skin. Their composition results in an imperfect lipid matrix, allowing increased drug encapsulation. Allopurinol (AP), a xanthine oxidase inhibitor, is characterized by low water solubility and high melting point, which has hampered its use through the topical route. In this work, AP was incorporated in a NLC formulation to enhance drug-carrier association and skin delivery as a topical approach to treat wounds. AP-NLC system was characterized in terms of size, charge, rheological behavior, and in vitro skin permeation. The in vitro cytotoxicity was evaluated using HaCaT cells. The wound healing efficacy of the AP-NLC formulation on animal skin lesions was evaluated in male Wistar rats. The AP-NLC presented a mean size of 193 ± 15 nm with a PdI of 0.240 ± 0.02, zeta potential values around −49.6 mV, and an encapsulation efficiency of 52.2%. The AP-NLC formulation presented an adequate profile to be used topically, since epidermal and dermal drug retention were achieved. No reduction in HaCaT cells viability was observed at the tested concentrations (AP < 10 μg/mL). The in vivo application of the AP-NLC formulation resulted in the regeneration of skin lesions when compared with non-treated controls.

The spontaneous healing of a tendon laceration results in the formation of scar tissue, which has lower functionality than the original tissue. Moreover, chronic non-healing tendon injuries frequently require surgical treatment. Several types of scaffolds have been developed using the tissue engineering approach, to complement surgical procedures and to enhance the healing process at the injured site. In this work, an electrospun hybrid tubular scaffold was designed to mimic tissue fibrous arrangement and extracellular matrix (ECM) composition, and to be extemporaneously loaded into the inner cavity with human platelet lysate (PL), with the aim of leading to complete post-surgery functional regeneration of the tissue for functional regeneration of the osteo–tendon interface. For this purpose, pullulan (P)/chitosan (CH) based polymer solutions were enriched with hydroxyapatite nanoparticles (HP) and electrospun. The nanofibers were collected vertically along the length of the scaffold to mimic the fascicle direction of the tendon tissue. The scaffold obtained showed tendon-like mechanical performance, depending on HP content and tube size. The PL proteins were able to cross the scaffold wall, and in vitro studies have demonstrated that tenocytes and osteoblasts are able to adhere to and proliferate onto the scaffold in the presence of PL; moreover, they were also able to produce either collagen or sialoproteins, respectively—important components of ECM. These results suggest that HP and PL have a synergic effect, endorsing PL-loaded HP-doped aligned tubular scaffolds as an effective strategy to support new tissue formation in tendon-to-bone interface regeneration.

Oligonucleotide therapeutics such as miRNAs and siRNAs represent a class of molecules developed to modulate gene expression by interfering with ribonucleic acids (RNAs) and protein synthesis. These molecules are characterized by strong instability and easy degradation due to nuclease enzymes. To avoid these drawbacks and ensure efficient delivery to target cells, viral and non-viral vectors are the two main approaches currently employed. Viral vectors are one of the major vehicles in gene therapy; however, the potent immunogenicity and the insertional mutagenesis is a potential issue for the patient. Non-viral vectors, such as polymeric nanocarriers, provide a safer and more efficient delivery of RNA-interfering molecules. The aim of this work is to employ PLGA core nanoparticles shell-coated with chitosan oleate as siRNA carriers. An siRNA targeted on HIV-1, directed against the viral Tat/Rev transcripts was employed as a model. The ionic interaction between the oligonucleotide’s moieties, negatively charged, and the positive surface charges of the chitosan shell was exploited to associate siRNA and nanoparticles. Non-covalent bonds can protect siRNA from nuclease degradation and guarantee a good cell internalization and a fast release of the siRNA into the cytosolic portion, allowing its easy activation.

Interstitial cystitis (IC) or painful bladder syndrome is a chronic dysfunction due to an inflammatory condition, characterized by bladder pain and urinary frequency. Currently, no gold standard therapy is available since IC does not respond to conventional ones. Given these premises, the aim of this work was the in vitro characterization of biological properties (mucoadhesion and anti-inflammatory activity) of a commercial product (HydealCyst–HydC) based on hyaluronic acid (HA) and the benzyl ester of HA (Hydeal-D®) intended for bladder instillation to restore and/or protect the urothelial layer of glycosamino glycans (GAGs). The in vitro characterization demonstrated that an interaction product is formed between HA and Hydeal-D® that has a role in the rheological behavior and mucoadhesive properties. HA was identified as a key component to form the mucoadhesive joint, while the interaction of HA with Hydeal-D® improved polysaccharide stability and prolonged the activity ex vivo. Moreover, HydC is cytocompatible with urothelial cells (HTB-4) and possesses an anti-inflammatory effect towards these cells by decreasing the secretion of IL-6 and IL-8, which were both increased in patients with IC, and by increasing the secretion of sulfated GAGs. These two findings, along with the resilience properties of the formulation due to mucoadhesion, suggest the active role of HydC in protecting and restoring urothelium homeostasis.

Chronic skin wounds are characterised by a non-healing process that makes necessary the application of wound dressings on the damaged area to promote and facilitate the recovery of skin’s physiological integrity. The aim of the present work is to develop a bioactive dressing that, once applied on the injured tissue, would exert antibacterial activity and promote adhesion and proliferation of fibroblasts. Nanofibres consisting of poly(lactic acid) (PLA) and essential oils (EOs) were electrospun and coated with a medium molecular weight chitosan (CS). Black pepper essential oil (BP-EO) or limonene (L), well-known for their antibacterial properties, were added to the PLA/acetone solution before electrospinning; phase separation phenomena occurred due to the poor solubility of the EOs in the PLA solution and led to fibres having surface nano-pores. The porous electrospun fibres were coated with CS to produce hydrophilic membranes that were easy to handle, biocompatible, and suited to promote cellular proliferation. The fibrous scaffolds were tested in terms of mechanical resistance, wettability, antibacterial activity, in-vitro cytotoxicity, and ability to promote fibroblasts’ adhesion and proliferation. The results obtained proved that the CS coating improved the hydrophilicity of the fibrous mats, enhanced EO’s antibacterial potential, and promoted cell adhesion and proliferation.

Tissue repair and regeneration is an interdisciplinary field focusing on developing bioactive substitutes aimed at restoring pristine functions of damaged, diseased tissues. Biomaterials, intended as those materials compatible with living tissues after in vivo administration, play a pivotal role in this area and they have been successfully studied and developed for several years. Namely, the researches focus on improving bio-inert biomaterials that well integrate in living tissues with no or minimal tissue response, or bioactive materials that influence biological response, stimulating new tissue re-growth. This review aims to gather and introduce, in the context of Italian scientific community, cutting-edge advancements in biomaterial science applied to tissue repair and regeneration. After introducing tissue repair and regeneration, the review focuses on biodegradable and biocompatible biomaterials such as collagen, polysaccharides, silk proteins, polyesters and their derivatives, characterized by the most promising outputs in biomedical science. Attention is pointed out also to those biomaterials exerting peculiar activities, e.g., antibacterial. The regulatory frame applied to pre-clinical and early clinical studies is also outlined by distinguishing between Advanced Therapy Medicinal Products and Medical Devices.

The complex pathophysiology of spinal cord injury may explain the current lack of an effective therapeutic approach for the regeneration of damaged neuronal cells and the recovery of motor functions. Many efforts have been performed to design and develop suitable scaffolds for spinal cord regeneration, keeping in mind that the reconstruction of a pro-regenerative environment is the key challenge for an effective neurogenesis. The aim of this review is to outline the main features of an ideal scaffold, based on biomaterials, produced by the electrospinning technique and intended for the spinal cord regeneration. An overview of the polymers more investigated in the production of neural fibrous scaffolds is also provided.

Glioblastoma multiforme (GBM) is one of the most prevalent and aggressive brain tumors for which there is currently no cure. A novel composite nanosystem (CN), consisting of chitosan-coated Solid Lipid Nanoparticles (c-SLN) embedded in O-carboxymethyl chitosan (O-CMCS)-containing nanofibers (NFs), was proposed as a potential tool for the local delivery of lipophilic anti-proliferative drugs. Coacervation was selected as a solvent-free method for the preparation of stearic acid (SA) and behenic acid (BA)-based SLN (SA-SLN and BA-SLN respectively). BA-SLN, containing 0.75% w/w BA sodium salt and 3% w/w poly(vinyl alcohol) (PVA), were selected for the prosecution of the work since they are characterized by the lowest size functional to their subsequent coating and incorporation in nanofibers. BA-SLN were coated with chitosan (CS) by means of a two-step coating method based on the physical absorption of positively charged CS chains on the SLN negative surface. Nile Red (NR), chosen as the hydrophobic model dye, was dissolved in a micellar solution of BA sodium salt and then added with a coacervating solution until pH ≅ 2.5 was reached. Immunocytochemistry analyses highlighted that CS-coated BA-SLN (c-BA-SLN) exhibited a higher accumulation in human glioblastoma cells (U-373) after 6 h than CS-free BA-SLN. Finally, the c-BA-SLN dispersion was blended with a solution consisting of freely soluble polymers (O-CMCS, poly(ethylene oxide) and poloxamer) and then electrospun to obtain NFs with a mean diameter equal to 850 nm. After the NFs dissolution in an aqueous media, c-BA-SLN maintained their physicochemical properties and zeta potential.

Periodontitis is a set of inflammatory conditions affecting the tissues surrounding the teeth predominantly sustained by bacterial infections. The aim of the work was the design and the development of scaffolds based on biopolymers to be inserted in the periodontal pocket to restore tissue integrity and to treat bacterial infections. Nanofibrous scaffolds were prepared by means of electrospinning. Gelatin was considered as base component and was associated to low and high molecular weight chitosans and alginate. The scaffolds were characterized by chemico–physical properties (morphology, solid state-FTIR and differential scanning calorimetry (DSC)-surface zeta potential and contact angle), and mechanical properties. Moreover, preclinical properties (cytocompatibility, fibroblast and osteoblast adhesion and proliferation and antimicrobial properties) were assessed. All the scaffolds were based on cylindrical and smooth nanofibers and preserved their nanofibrous structure upon hydration independently of their composition. They possessed a high degree of hydrophilicity and negative zeta potentials in a physiological environment, suitable surface properties to enhance cell adhesion and proliferation and to inhibit bacteria attachment. The scaffold based on gelatin and low molecular weight chitosan proved to be effective in vitro to support both fibroblasts and osteoblasts adhesion and proliferation and to impair the proliferation of Streptococcus mutans and Aggregatibacter actinomycetemcomitans, both pathogens involved in periodontitis.

The tendon is a highly aligned connective tissue that transmits force from muscle to bone. Each year, more than 32 million tendon injuries have been reported, in fact, tendinopathies represent at least 50% of all sports injuries, and their incidence rates have increased in recent decades due to the aging population. Current clinical grafts used in tendon treatment are subject to several restrictions and there is a significant demand for alternative engineered tissue. For this reason, innovative strategies need to be explored. Tendon replacement and regeneration are complex since scaffolds need to guarantee an adequate hierarchical structured morphology and mechanical properties to stand the load. Moreover, to guide cell proliferation and growth, scaffolds should provide a fibrous network that mimics the collagen arrangement of the extracellular matrix in the tendons. This review focuses on tendon repair and regeneration. Particular attention has been devoted to the innovative approaches in tissue engineering. Advanced manufacturing techniques, such as electrospinning, soft lithography, and three-dimensional (3D) printing, have been described. Furthermore, biological augmentation has been considered, as an emerging strategy with great therapeutic potential.

Injuries to the nervous system affect more than one billion people worldwide, and dramatically impact on the patient’s quality of life. The present work aimed to design and develop a gellan gum (GG)-based composite system for the local delivery of the neuroprotective sigma-1 receptor agonist, 1-[3-(1,1′-biphen)-4-yl] butylpiperidine (RC-33), as a potential tool for the treatment of tissue nervous injuries. The system, consisting of cross-linked electrospun nanofibers embedded in a RC-33-loaded freeze-dried matrix, was designed to bridge the lesion gap, control drug delivery and enhance axonal regrowth. The gradual matrix degradation should ensure the progressive interaction between the inner fibrous mat and the surrounding cellular environment. Nanofibers, prepared by electrospinning polymeric solutions containing GG, two different grades of poly (ethylene oxide) and poloxamer, were cross-linked with calcium ions. GG-based matrices, loaded with different amounts of RC-33, were prepared by freeze-drying. Dialysis studies and solid-state characterization pointed out the formation of an interaction product between GG and RC-33. RC-33-loaded freeze-dried matrices were characterized by the capability to absorb a high buffer content, forming a gel with marked viscoelastic properties, and by RC-33 controlled release properties. The presence of cross-linked nanofibers increased matrix mechanical resistance.

This work presents the development of multifunctional therapeutic membranes based on a high-performance block copolymer scaffold formed by polyether (PE) and polyamide (PA) units (known as PEBA) and layered double hydroxide (LDH) biomaterials, with the aim to study their uses as wound dressings. Two LDH layer compositions were employed containing Mg2+ or Zn2+, Fe3+ and Al3+ cations, intercalated with chloride anions, abbreviated as Mg-Cl or Zn-Cl, or intercalated with naproxenate (NAP) anions, abbreviated as Mg-NAP or Zn-NAP. Membranes were structurally and physically characterized, and the in vitro drug release kinetics and cytotoxicity assessed. PEBA-loading NaNAP salt particles were also prepared for comparison. Intercalated NAP anions improved LDH–polymer interaction, resulting in membranes with greater mechanical performance compared to the polymer only or to the membranes containing the Cl-LDHs. Drug release (in saline solution) was sustained for at least 8 h for all samples and release kinetics could be modulated: a slower, an intermediate and a faster NAP release were observed from membranes containing Zn-NAP, NaNAP and Mg-NAP particles, respectively. In general, cell viability was higher in the presence of Mg-LDH and the membranes presented improved performance in comparison with the powdered samples. PEBA containing Mg-NAP sample stood out among all membranes in all the evaluated aspects, thus being considered a great candidate for application as multifunctional therapeutic dressings.

Collagen, thanks to its biocompatibility, biodegradability and weak antigenicity, is widely used in dressings and scaffolds, also as electrospun fibers. Its mechanical stability can be improved by adding polycaprolactone (PCL), a synthetic and biodegradable aliphatic polyester. While previously collagen/PCL combinations were electrospun in solvents such as hexafluoroisopropanol (HFIP) or trifluoroethanol (TFE), more recently literature describes collagen/PCL nanofibers obtained in acidic aqueous solutions. A good morphology of the fibers represents in this case still a challenge, especially for high collagen/PCL ratios. In this work, thanks to preliminary rheological and physicochemical characterization of the solutions and to a Design of Experiments (DOE) approach on process parameters, regular and dimensionally uniform fibers were obtained with collagen/PCL ratios up to 1:2 and 1:1 w/w. Collagen ratio appeared relevant for mechanical strength of dry and hydrated fibers. WAXS and FTIR analysis showed that collagen denaturation is related both to the medium and to the electrospinning process. After one week in aqueous environment, collagen release was complete and a concentration dependent stimulatory effect on fibroblast growth was observed, suggesting the fiber suitability for wound healing. The positive effect of collagen on mechanical properties and on fibroblast biocompatibility was confirmed by a direct comparison of nanofiber performance after collagen substitution with gelatin.

Inorganic hydrogels formulated with spring waters and clay minerals are used to treat musculoskeletal disorders and skin affections. Their underlying mechanism of action for skin disorders is not clear, although it is usually ascribed to the chemical composition of the formulation. The aim of this study was to assess the composition and in vitro release of elements with potential wound healing effects from hydrogels prepared with two nanoclays and natural spring water. In vitro Franz cell studies were used and the element concentration was measured by inductively coupled plasma techniques. Biocompatibility studies were used to evaluate the potential toxicity of the formulation against fibroblasts. The studied hydrogels released elements with known therapeutic interest in wound healing. The released ratios of some elements, such as Mg:Ca or Zn:Ca, played a significant role in the final therapeutic activity of the formulation. In particular, the proliferative activity of fibroblasts was ascribed to the release of Mn and the Zn:Ca ratio. Moreover, the importance of formulative studies is highlighted, since it is the optimal combination of the correct ingredients that makes a formulation effective.

In situ gelling drug delivery systems have gained enormous attention over the last decade. They are in a sol-state before administration, and they are capable of forming gels in response to different endogenous stimuli, such as temperature increase, pH change and the presence of ions. Such systems can be administered through different routes, to achieve local or systemic drug delivery and can also be successfully used as vehicles for drug-loaded nano- and microparticles. Natural, synthetic and/or semi-synthetic polymers with in situ gelling behavior can be used alone, or in combination, for the preparation of such systems; the association with mucoadhesive polymers is highly desirable in order to further prolong the residence time at the site of action/absorption. In situ gelling systems include also solid polymeric formulations, generally obtained by freeze-drying, which, after contact with biological fluids, undergo a fast hydration with the formation of a gel able to release the drug loaded in a controlled manner. This review provides an overview of the in situ gelling drug delivery systems developed in the last 10 years for non-parenteral administration routes, such as ocular, nasal, buccal, gastrointestinal, vaginal and intravesical ones, with a special focus on formulation composition, polymer gelation mechanism and in vitro release studies.

Chronic wounds, such as pressure ulcers, diabetic ulcers, venous ulcers and arterial insufficiency ulcers, are lesions that fail to proceed through the normal healing process within a period of 12 weeks. The treatment of skin chronic wounds still represents a great challenge. Wound medical devices (MDs) range from conventional and advanced dressings, up to skin grafts, but none of these are generally recognized as a gold standard. Based on recent developments, this paper reviews nanotechnology-based medical devices intended as skin substitutes. In particular, nanofibrous scaffolds are promising platforms for wound healing, especially due to their similarity to the extracellular matrix (ECM) and their capability to promote cell adhesion and proliferation, and to restore skin integrity, when grafted into the wound site. Nanotechnology-based scaffolds are emphasized here. The discussion will be focused on the definition of critical quality attributes (chemical and physical characterization, stability, particle size, surface properties, release of nanoparticles from MDs, sterility and apyrogenicity), the preclinical evaluation (biocompatibility testing, alternative in vitro tests for irritation and sensitization, wound healing test and animal wound models), the clinical evaluation and the CE (European Conformity) marking of nanotechnology-based MDs.

Background: hydrogels prepared with natural inorganic excipients and spring waters are commonly used in medical hydrology. Design of these clay-based formulations continues to be a field scarcely addressed. Safety and wound healing properties of different fibrous nanoclay/spring water hydrogels were addressed. Methods: in vitro biocompatibility, by means of MTT assay, and wound healing properties were studied. Confocal Laser Scanning Microscopy was used to study the morphology of fibroblasts during the wound healing process. Results: all the ingredients demonstrated to be biocompatible towards fibroblasts. Particularly, the formulation of nanoclays as hydrogels improved biocompatibility with respect to powder samples at the same concentration. Spring waters and hydrogels were even able to promote in vitro fibroblasts motility and, therefore, accelerate wound healing with respect to the control. Conclusion: fibrous nanoclay/spring water hydrogels proved to be skin-biocompatible and to possess a high potential as wound healing formulations. Moreover, these results open new prospects for these ingredients to be used in new therapeutic or cosmetic formulations.

Infections in nonhealing wounds remain one of the major challenges. Recently, nanomedicine approach seems a valid option to overcome the antibiotic resistance mechanisms. The aim of this study was the development of three types of polysaccharide-based scaffolds (chitosan-based (CH), chitosan/chondroitin sulfate-based (CH/CS), chitosan/hyaluronic acid-based (CH/HA)), as dermal substitutes, to be loaded with norfloxacin, intended for the treatment of infected wounds. The scaffolds have been loaded with norfloxacin as a free drug (N scaffolds) or in montmorillonite nanocomposite (H—hybrid-scaffolds). Chitosan/glycosaminoglycan (chondroitin sulfate or hyaluronic acid) scaffolds were prepared by means of electrospinning with a simple, one-step process. The scaffolds were characterized by 500 nm diameter fibers with homogeneous structures when norfloxacin was loaded as a free drug. On the contrary, the presence of nanocomposite caused a certain degree of surface roughness, with fibers having 1000 nm diameters. The presence of norfloxacin–montmorillonite nanocomposite (1%) caused higher deformability (90–120%) and lower elasticity (5–10 mN/cm2), decreasing the mechanical resistance of the systems. All the scaffolds were proven to be degraded via lysozyme (this should ensure scaffold resorption) and this sustained the drug release (from 50% to 100% in 3 days, depending on system composition), especially when the drug was loaded in the scaffolds as a nanocomposite. Moreover, the scaffolds were able to decrease the bioburden at least 100-fold, proving that drug loading in the scaffolds did not impair the antimicrobial activity of norfloxacin. Chondroitin sulfate and montmorillonite in the scaffolds are proven to possess a synergic performance, enhancing the fibroblast proliferation without impairing norfloxacin’s antimicrobial properties. The scaffold based on chondroitin sulfate, containing 1% norfloxacin in the nanocomposite, demonstrated adequate stiffness to sustain fibroblast proliferation and the capability to sustain antimicrobial properties to prevent/treat nonhealing wound infection during the healing process.

Polymeric micelles based on amphiphilic polysaccharides have some advantages as a carrier of poorly soluble lipophilic drugs thanks to their characteristic "core–shell" structure. Previously, ionic polymeric micelles based on chitosan and fatty acids have been developed. The aim of the present study was the preparation and characterization of hyaluronic acid (HA) derivatives by direct ionic interaction between the HA carboxylic groups and the amine groups of dodecyl amine (DDA) and hexadecyl amine (HDA). The HA–HDA polymeric micelles were loaded with a poorly soluble hydrophobic antifungal drug, clotrimazole (CLO). A 23 full factorial experimental design was used to evaluate the effect of the following factors: HA/HDA ratio from 1:0.25 to 1:0.75, cholesterol (CHOL%) as percentage of HA from 10% to 30%, and preparation temperature from 20 to 40 °C. As dependent variables (responses), nanoparticle dimensions and clotrimazole concentration in the final colloidal dispersion were considered. To optimize the drug final concentration, the design was therefore expanded into a rotatable central composite design (CCD). The effects of the formulation variables and the composition of the optimized formulation were confirmed by a mixture design. Physicochemical characterization of the optimized formulation was performed, confirming the ionic interaction between the polysaccharide and the HDA.

The increase in life expectancy and the increasing prevalence of diabetic disease and venous insufficiency lead to the increase of chronic wounds. The prevalence of ulcers ranges from 1% in the adult population to 3−5% in the over 65 years population, with 3−5.5% of the total healthcare expenditure, as recently estimated. The aim of this work was the design and the development of electrospun scaffolds, entirely based on biopolymers, loaded with montmorillonite (MMT) or halloysite (HNT) and intended for skin reparation and regeneration, as a 3D substrate mimicking the dermal ECM. The scaffolds were manufactured by means of electrospinning and were characterized for their chemico-physical and preclinical properties. The scaffolds proved to possess the capability to enhance fibroblast cells attachment and proliferation with negligible proinflammatory activity. The capability to facilitate the cell adhesion is probably due to their unique 3D structure which are assisting cell homing and would facilitate wound healing in vivo.

The present work proposed a novel therapeutic platform with both neuroprotective and neuroregenerative potential to be used in the treatment of spinal cord injury (SCI). A dual-functioning scaffold for the delivery of the neuroprotective S1R agonist, RC-33, to be locally implanted at the site of SCI, was developed. RC-33-loaded fibers, containing alginate (ALG) and a mixture of two different grades of poly(ethylene oxide) (PEO), were prepared by electrospinning. After ionotropic cross-linking, fibers were incorporated in chitosan (CS) films to obtain a drug delivery system more flexible, easier to handle, and characterized by a controlled degradation rate. Dialysis equilibrium studies demonstrated that ALG was able to form an interaction product with the cationic RC-33 and to control RC-33 release in the physiological medium. Fibers loaded with RC-33 at the concentration corresponding to 10% of ALG maximum binding capacity were incorporated in films based on CS at two different molecular weights—low (CSL) and medium (CSM)—solubilized in acetic (AA) or glutamic (GA) acid. CSL- based scaffolds were subjected to a degradation test in order to investigate if the different CSL salification could affect the film behavior when in contact with media that mimic SCI environment. CSL AA exhibited a slower biodegradation and a good compatibility towards human neuroblastoma cell line.

Local administration of vaginal probiotics, especially lactobacilli, has been recently proposed as an effective prevention strategy against candidosis recurrences, which affect 40−50% of women. In this context, the aim of the present work was the development of a mucoadhesive in situ gelling formulation for the vaginal administration of Lactobacillus gasseri. Mixtures of poloxamer 407 (P407) and methylcellulose (MC), two thermosensitive polymers, were prepared and subjected to rheological analyses for the assessment of their sol/gel transition temperature. The association of P407 (15% w/w) with MC (1.5% w/w) produced an increase in gelation extent at 37 °C even after dilution in simulated vaginal fluid (SVF). The presence of 0.5% w/w pectin (PEC) produced a reduction of vehicle pH and viscosity at 25 °C that is the vehicle resistance to flow during administration. The presence of a low concentration of xyloglucan (XYL) (0.25% w/w) increases the mucoadhesive properties and the capability to gelify at 37 °C of the formulation after dilution with SVF. A three-component (P407/MC/PEC; 3cM) and a four-component (P407/MC/PEC/XYL; 4cM) mixture were selected as promising candidates for the delivery of L. gasseri to the vaginal cavity. They were able to preserve L. gasseri viability and were cytocompatible towards the HeLa cell line.

Chitosan oleate (CS-OA), a chitosan salt with amphiphilic properties, has demonstrated the ability to self-assemble in aqueous environment to give polymeric micelles useful to load poorly soluble drugs. More recently, CS-OA was proposed to stabilize nanoemulsions during the preparation by emulsification and solvent evaporation of poly lactic-glycolic acid (PLGA) nanoparticles (NPs) loaded with curcumin. Positive mucoadhesive behavior and internalization properties were demonstrated for these NPs attributable to the presence of positive charge at the NP surface. In the present paper, two CS-OA-based nanosystems, micelles and PLGA NPs, were compared with the aim of elucidating their physico-chemical characteristics, and especially their interaction with cell substrates. The two systems were loaded with resveratrol (RSV), a hydrophobic polyphenol endowed with anti-cancerogenic, anti-inflammatory, and heart/brain protective effects, but with low bioavailability mainly due to poor aqueous solubility. Calorimetric analysis and X-ray spectra demonstrated amorphization of RSV, confirming its affinity for hydrophobic domains of polymeric micelles and PLGA core of NPs. TGA decomposition patterns suggest higher stability of PLGA-NPs compared with polymeric micelles, that anyway resulted more stable than expected, considering the RSV release profiles, and the cell line interaction results.

Cutaneous wounds represent a major issue in medical care, with approximately 300 million chronic and 100 million traumatic wound patients worldwide, and microbial infections slow the healing process. The aim of this work was to develop electrospun scaffolds loaded with silver nanoparticles (AgNPs) to enhance cutaneous healing, preventing wound infections. AgNPs were directly added to polymeric blends based on chitosan (CH) and pullulan (PUL) with hyaluronic acid (HA) or chondroitin sulfate (CS) to be electrospun obtaining nanofibrous scaffolds. Moreover, a scaffold based on CH and PUL and loaded with AgNPs was prepared as a comparison. The scaffolds were characterized by chemico−physical properties, enzymatic degradation, biocompatibility, and antimicrobial properties. All the scaffolds were based on nanofibers (diameters about 500 nm) and the presence of AgNPs was evidenced by TEM and did not modify their morphology. The scaffold degradation was proven by means of lysozyme. Moreover, the AgNPs loaded scaffolds were characterized by a good propensity to promote fibroblast proliferation, avoiding the toxic effect of silver. Furthermore, scaffolds preserved AgNP antimicrobial properties, although silver was entrapped into nanofibers. Chitosan/chondroitin sulfate scaffold loaded with AgNPs demonstrated promotion of fibroblast proliferation and to possess antimicrobial properties, thus representing an interesting tool for the treatment of chronic wounds.

The aim of the present work was to load a Hibiscus sabdariffa (HS) hydroalcoholic extract into in situ gelling formulations for the treatment of oral mucositis and esophagitis. Such formulations, selected as the most promising options in a previous work of ours, were composed by κ-carrageenan (κ-CG), a sulfated marine polymer able to gelify in presence of saliva ions, hydroxypropyl cellulose (HPC), used as mucoadhesive agent, and CaCl2, salt able to enhance the interaction κ-CG/saliva ions. HS extract, which is rich in phytochemicals such as polyphenols, polysaccharides and organic acids, was selected due to its antioxidant and anti-inflammatory properties. For HS extraction, three different methodologies (maceration, Ultrasound Assisted Extraction (UAE) and Microwave Assisted Extraction (MAE)) were compared in terms of extraction yield and extract antioxidant activity, revealing that MAE was the best procedure. Rheological and mucoadhesive properties of HS-loaded formulations were investigated. Such formulations were characterized by a low viscosity at 25 °C, guaranteeing an easy administration, a proper in situ gelation behavior and marked elastic and mucoadhesive properties at 37 °C, functional to a protective action towards the damaged mucosa. Finally, the biocompatibility and the proliferative effect of HS-loaded formulations, as well as their antioxidant and anti-inflammatory properties, were proved in vitro on human dermal fibroblasts.

Oral mucositis and esophagitis represent the most frequent and clinically significant complications of cytoreductive chemotherapy and radiotherapy, which severely compromise the patient quality of life. The local application of polymeric gels could protect the injured tissues, alleviating the most painful symptoms. The present work aims at developing in situ gelling formulations for the treatment of oral mucositis and esophagitis. To reach these targets, κ-carrageenan (κ-CG) was selected as a polymer having wound healing properties and able to gelify in the presence of saliva ions, while hydroxypropyl cellulose (HPC) was used to improve the mucoadhesive properties of the formulations. CaCl2 was identified as a salt able to enhance the interaction between κ-CG and saliva ions. Different salt and polymer concentrations were investigated in order to obtain a formulation having the following features: (i) low viscosity at room temperature to facilitate administration, (ii) marked elastic properties at 37 °C, functional to a protective action towards damaged tissues, and (iii) mucoadhesive properties. Prototypes characterized by different κ-CG, HPC, and CaCl2 concentrations were subjected to a thorough rheological characterization and to in vitro mucoadhesion and washability tests. The overall results pointed out the ability of the developed formulations to produce a gel able to interact with saliva ions and to adhere to the biological substrates.

The blood⁻brain barrier (BBB) plays a fundamental role in protecting the brain from toxic substances and therefore also controls and restricts the entry of therapeutic agents. The nasal administration of drugs using the nose-to-brain pathway allows direct drug targeting into the brain, avoiding the first-pass effect and bypassing the BBB. Through the nasal route, the drug can access the brain directly along the trigeminal and olfactory nerves, which are located in the upper part of the nasal cavity. Nanoemulsions are formulations belonging to the field of nanomedicine. They consist of emulsions (commonly oil in water) stabilized by one or more surfactants—and eventually co-surfactants—delivered in droplets of small dimensions (sizes of 100⁻300 nm or less) with a high surface area. A mucoadhesive polymer such as chitosan can be added to the formulation to impair rapid nasal clearance. Nanoemulsions represent promising formulations to deliver drugs directly into the brain through the intranasal route. Therefore, they can be used as a possible alternative to oral administration, avoiding problems such as low solubility in water, poor bioavailability, enzymatic degradation and slow onset of action. This review focuses the present situation in literature regarding the use of nanoemulsions for nose-to-brain targeting, with particular attention to recent publications. Nasal nanoemulsions appear to be effective, non-invasive and safe drug delivery systems to achieve brain targeting for the treatment of neurological diseases.

Dry eye disease is a relatively common ocular problem, which causes eye discomfort and visual disorders leading to a decrease in the quality of life. The aim of this study was to find a possible excipient for eye drop formulations, which is able to stabilize the tear film. A cationic thiolated polyaspartamide polymer, poly[(N-mercaptoethylaspartamide)-co-(N-(N′,N′-dimethylaminoethyl)aspartamide)] (ThioPASP-DME), was used as a potential vehicle. Besides satisfying the basic requirements, the chemical structure of ThioPASP-DME is similar to those of ocular mucins as it is a protein-like polymer bearing a considerable number of thiol groups. The solution of the polymer is therefore able to mimic the physiological properties of the mucins and it can interact with the mucus layer via disulphide bond formation. The resultant mucoadhesion provides a prolonged residence time and ensures protective effect for the corneal/conjunctival epithelium. ThioPASP-DME also has an antioxidant effect due to the presence of the thiol groups. The applicability of ThioPASP-DME as a potential excipient in eye drops was determined by means of ocular compatibility tests and through examinations of the interactions with the mucosal surface. The results indicate that ThioPASP-DME can serve as a potential eye drop excipient for the therapy of dry eye disease.

The aim of the present work was to investigate how the molecular weight (MW) of poly(ethylene oxide) (PEO), a synthetic polymer able to improve alginate (ALG) electrospinnability, could affect ALG-based fiber morphology and mechanical properties. Two PEO grades, having different MWs (high, h-PEO, and low, l-PEO) were blended with ALG: the concentrations of both PEOs in each mixture were defined so that each h-PEO/l-PEO combination would show the same viscosity at high shear rate. Seven ALG/h-PEO/l-PEO mixtures were prepared and characterized in terms of viscoelasticity and conductivity and, for each mixture, a complex parameter rH/rL was calculated to better identify which of the two PEO grades prevails over the other in terms of exceeding the critical entanglement concentration. Thereafter, each mixture was electrospun by varying the process parameters; the fiber morphology and mechanical properties were evaluated. Finally, viscoelastic measurements were performed to verify the formation of intermolecular hydrogen bonds between the two PEO grades and ALG. rH/rL has been proved to be the parameter that better explains the effect of the electrospinning conditions on fiber dimension. The addition of a small amount of h-PEO to l-PEO was responsible for a significant increase in fiber mechanical resistance, without affecting the nano-scale fiber size. Moreover, the mixing of h-PEO and l-PEO improved the interaction with ALG, resulting in an increase in chain entanglement degree that is functional in the electrospinning process.