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Chitosan and poly(3-hydroxybutyrate) are non-toxic, biodegradable, and biocompatible polymers extensively used in regenerative medicine. However, it is unknown whether the chemical combination of these polymers can produce a biomaterial that induces an appropriate cellular response in vitro in mammalian cells. This study aimed to test the ability of a novel salt-leached polyurethane scaffold of chitosan grafted with poly(3-hydroxybutyrate) to support the growth of three mammalian cell lines of different origin: a) HEK-293 cells, b) i28 mouse myoblasts, and c) human dermal fibroblasts. The viability of the cells was assessed by either evaluation of their capacity to maintain the expression of the green fluorescent protein by adenoviral transduction or by esterase activity and plasma membrane integrity. The results indicated that the three cell lines attached well to the scaffold; however, when i28 cells were induced to differentiate, they did not produce morphologically distinct myofibers, and cell growth ceased. In conclusion, the findings reveal that, altogether, these observations suggest that this foam scaffold supports cell growth and proliferation but may not apply to all cell types. Hence, one crucial question yet to be resolved is a poly (saccharide-ester-urethane) derivative with a nano-topography that elicits a similar cellular response for different biological environments.

The research of self-healable polymers intended for medical use has increased in the last 20 years. These materials can self-repair and recover their functionality after damage; thus, they are of significant interest in diverse academic areas, including the biomedical field. In this regard, numerous synthetic and natural polymers are being used to develop self-healing hydrogels for tissue engineering applications, particularly for the restoration of bones, cartilage, skin, and even the central nervous system. These materials possess distinct advantages; for example, natural polymers are usually biocompatible and biodegradable, whereas synthetic polymers could be more suitable when rigid hydrogels with fast kinetics are required. Moreover, the intrinsic reticular matrix of these self-healing systems allows the load of diverse drugs and their controlled release. Remarkably, polymers may be mixed to obtain hydrogels with enhanced mechanical and biological properties. The elaboration of self-healable hydrogels is carried out through either covalent crosslinking or non-covalent crosslinking; the selection of the method depends on many factors, including the required mechanical properties and desired use. Although some articles have reviewed self-healing hydrogels, papers focused on utilizing these systems in tissue engineering are scarce. In this article, we perform a concise description of fabrication methods of self-healing hydrogels and the employed polymers. Furthermore, we provide numerous examples of hydrogels intended for biomedical purposes and discuss their key functional properties. Our main objective was to point out the most recent progress in utilizing self-healing polymers in tissue engineering.

Oxidative stress is the imbalance between reactive oxygen species (ROS) production, and accumulation and the ability of a biological system to clear these reactive products. This imbalance leads to cell and tissue damage causing several disorders in human body, such as neurodegeneration, metabolic problems, cardiovascular diseases, and cancer. Cucurbitaceae family consists of about 100 genera and 1,000 species of plants including mostly tropical, annual or perennial, monoecious, and dioecious herbs. The plants from Cucurbita species are rich sources of phytochemicals and act as a rich source of antioxidants. The most important phytochemicals present in the cucurbits are cucurbitacins, saponins, carotenoids, phytosterols, and polyphenols. These bioactive phyto-constituents are responsible for the pharmacological effects including antioxidant, antitumor, antidiabetic, hepatoprotective, antimicrobial, anti-obesity, diuretic, anti-ulcer activity, and antigenotoxic. A wide number of in vitro and in vivo studies have ascribed these health-promoting effects of Cucurbita genus. Results of clinical trials suggest that Cucurbita provides health benefits for diabetic patients, patients with benign prostate hyperplasia, infertile women, postmenopausal women, and stress urinary incontinence in women. The intend of the present review is to focus on the protective role of Cucurbita spp. phytochemicals on oxidative stress-related disorders on the basis of preclinical and human studies. The review will also give insights on the in vitro and in vivo antioxidant potential of the Cucurbitaceae family as a whole.

Bacterial vaginosis is a vaginal infection that affects 60% of women of reproductive age worldwide. It is mainly caused by the bacterium Gardnerella vaginalis and is a factor that increases the probability of getting sexually transmitted diseases. We aimed to develop a new pharmaceutical form for the treatment of vaginal infections. We employed the solving-casting method to fabricate a polymeric film with Xanthan gum, a natural polymer produced by the bacterium Xanthomonas campestris, and metronidazole, one of the most commonly used drugs for vaginal infections. In order to characterize the film, we measured pH, dose uniformity, dissolution profile, and the percentage of swelling. Moreover, we performed a thermogravimetric analysis and scanning electron microscopy. The results demonstrated a pH suitable for vaginal application and uniform distribution of the drug in the film. Also, the formulation exhibited a high percentage of swelling and a slow release of the drug in a simulated vaginal fluid medium. All these attributes indicated that the manufactured film has ideal characteristics to be used and administered vaginally. It could be an excellent alternative to treat bacterial vaginosis and also improve user adherence.

Hyaluronic acid (HA) is one of the most attractive natural polymers employed in biomaterials with biological applications. This polysaccharide is found in different tissues of the body because it is a natural component of the extracellular matrix; furthermore, it has crucial functions in cell growth, migration, and differentiation. Since its biological characteristics, HA has been utilized for the new biomaterial's development for tissue engineering, such as hydrogels. These hydrophilic macromolecular networks have gained significant attention due to their unique properties, making them potential candidates to be applied in biomedical fields. Different mechanisms to obtain hydrogels have been described. However, the research of new non-toxic methods has been growing in recent years. In this study, we prepared a new hydrogel of HA and polyvinyl alcohol by the cost-effective technique of cross-linking by gamma irradiation. The hydrogel was elaborated for the first time and was characterized by several methods such as Fourier Transform Infrared Spectroscopy, Differential Scanning Calorimetry, Thermogravimetric Analysis, and Scanning Electron Microscopy. Likewise, we evaluated the cytotoxicity of the biomaterial and its influence on cell migration in human fibroblasts. Furthermore, we provide preliminary evidence of the wound closure effect in a cellular wound model. The novel hydrogel offers an increase of HA stability with the potential to expand the useful life of HA in its different medical applications.

Elastin is one of the main components of the extracellular matrix; it provides resistance and elasticity to a variety of tissues and organs of the human body, besides participating in cellular signaling. On the other hand, elastin-derived peptides are synthetic biopolymers with a similar conformation and structure to elastin, but these possess the advantage of solubility in aqueous mediums. Due to their biological activities and physicochemical properties, elastin and related peptides may be applied as biomaterials to develop diverse biomedical devices, including scaffolds, hydrogels, and drug delivery systems for tissue engineering. Likewise, the combination of elastin with natural or synthetic polymers has demonstrated to improve the mechanical properties of biomedical products and drug delivery systems. Here we comprehensively describe the physicochemical properties and physiological functions of elastin. Moreover, we offer an overview of the use of elastin and its derivative polymers as biomaterials to develop scaffolds and hydrogels for tissue engineering. Finally, we discuss some perspectives on the employment of these biopolymers to fabricate new biomedical products.

The objective of this study was to evaluate the effectiveness of a combination of UV-C disinfection treatment and a nano-coating lemon essential oil nanocapsules. The nanocapsules were prepared by ionic gelation with an alginate-pectin wall and the lemon essential oil had a particle size of 219 ± 22 nm and a zeta potential of −7.91 ± 0.18 mV. The lemon essential oil had an encapsulation efficiency of 68.19 ± 1.18%. The fresh-cut cucumber was stored for 15 days at 4 °C. Six formulations of nanocapsules were evaluated, and hydroxypropyl methylcellulose was used as matrix polysaccharide in four coatings. Three formulations were treated with UV-C at 4.5 kJ/m2. The results showed that the combination of UV-C and nano-coatings (lemon essential oil = 200 mg/L) increased the shelf life by up to 15 days. Using UV-C and nano-coatings, the ∆E value was 7.12 at the end of the storage period, while the Control samples had an ∆E of 28.1. With nano-coating treatment, the amount of polyphenols decreased by 23% within 9 days. In contrast, with combined UV-C and nano-coating treatment, the amount of polyphenols was reduced by 38.84% within 15 days. The antioxidant capacity remained stable at 459 μmol TE/100 g for the fresh product when the combined treatment was used. A good correlation was also observed between the increasing of the fruit’s shelf life and decreasing of its enzymatic activity. The inclusion of UV-C treatment contributed to the reduction in the initial total bacteria at 3.30 log CFU/g and its combination with nano-coatings helped in the control of microbial growth during storage.

Resveratrol is a polyphenolic stilbene derivative widely present in grapes and red wine. Broadly known for its antioxidant effects, numerous studies have also indicated that it exerts anti-inflammatory and antiaging abilities and a great potential in cancer therapy. Regrettably, the oral administration of resveratrol has pharmacokinetic and physicochemical limitations such as hampering its effects so that effective administration methods are demanding to ensure its efficiency. Thus, the present review explores the published data on the application of resveratrol nanoformulations in cancer therapy, with the use of different types of nanodelivery systems. Mechanisms of action with a potential use in cancer therapy, negative effects, and the influence of resveratrol nanoformulations in different types of cancer are also highlighted. Finally, the toxicological features of nanoresveratrol are also discussed.

Curcumin is the major polyphenolic compound of Curcuma longa. It has been found to possess anti-inflammatory and antioxidant activities. The latter property could be exploited as a treatment for neuronal diseases. However, its medical application is limited due to its poor solubility in aqueous phase and fast degradation. Nanoparticle-based drug-delivery platforms are suitable carriers for overcoming pharmacokinetic limitations and enhancing drug transport, and they exhibit minimal toxicity. The purpose of this article was to assemble curcumin-loaded poly-e-caprolactone nanoparticles by means of the emulsification-diffusion method using Pluronic® F68 as a stabilizer for in vitro evaluation in MIO-M1 and SH-SY5Y cells, which are cells involved on neuronal diseases. The curcumin-loaded nanoparticles obtained, with a mean particle size of 149.0 ± 2.2 nm, were characterized by physicochemical and biological techniques. Results showed that curcumin was loaded with 96% efficacy. Additionally, the cytotoxicity of the nanoparticles was evaluated in vitro in MIO-M1 and SH-SY5Y cells, demonstrating adequate biocompatibility. Cell uptake was analyzed with MIO-M1 cells, exhibiting high internalization rate. These results indicate that curcumin-loaded nanoparticles could be a potential alternative treatment for neuronal diseases as spinocerebellar ataxias and Parkinson's disease.

The combination of spectroscopy studies with simulation models can be a useful tool to predict the applications of macromolecules. However, it is currently unknown if applications of polyhydroxyalkanoate (PHA) derivatives can be determined with this methodology. Here, we used a new nuclear magnetic resonance (NMR) technique to structurally characterize poly (3-hydroxybutyrate) grafted with 2-aminoethyl methacrylate and combined the experimental results with those of molecular dynamic simulations. The NMR results show the possible grafting mechanism and final structure of the grafted polymer. Quantum and molecular dynamic simulations of the proposed structures were carried out to determine the reactive sites, hydrogen bonds, and physical movements of atoms. Using the information gathered, the application of the polymer as a scaffold for cell growth was discussed. It was concluded that this approach would be advantageous to achieve considerable savings in cost and time while developing potential applications of these bio-derived polyesters.

Surfactants are essential in the manufacture of polymeric nanoparticles by emulsion formation methods and to preserve the stability of carriers in liquid media. The deposition of non-ionic surfactants at the interface allows a considerable reduction of the globule of the emulsion with high biocompatibility and the possibility of oscillating the final sizes in a wide nanometric range. Therefore, this review presents an analysis of the three principal non-ionic surfactants utilized in the manufacture of polymeric nanoparticles; polysorbates, poly(vinyl alcohol), and poloxamers. We included a section on general properties and uses and a comprehensive compilation of formulations with each principal non-ionic surfactant. Then, we highlight a section on the interaction of non-ionic surfactants with biological barriers to emphasize that the function of surfactants is not limited to stabilizing the dispersion of nanoparticles and has a broad impact on pharmacokinetics. Finally, the last section corresponds to a recommendation in the experimental approach for choosing a surfactant applying the systematic methodology of Quality by Design.

Periodontal pain is a public health problem derived from different conditions, including periodontal diseases, prosthetic complications, and even extractions performed by dentist. There are various treatments to control acute dental pain, being the administration of analgesics, such as Lysine Clonixinate (LC), a common practice. Unfortunately, higher and repeated dosages are usually required. The purpose of this work was to develop a prolonged release pharmaceutical form as an alternative treatment for dental pain. Hence, we conceived a film based on guar gum and loaded different concentrations of LC. We evaluated the film's appearance, brittleness, strength, and flexibility, and then chose one formulation for adequate characteristics. Subsequently, we assessed the morphology, thermal behavior, and swelling properties of the films (LC-free and –loaded). Finally, we performed the release studies of LC from the films in vitro using a simulated saliva medium and employed several mathematical models to evaluate the release kinetics. Guar gum is a natural polymer obtained from the endosperm of Cyamopsis tetragonolobus that presents properties such as biosafety, biocompatibility, and biodegradability. Thus, it represents a potential excipient for use in pharmaceutical formulations. Moreover, our results revealed that the LC-loaded film presented a high adherence, suitable swelling behavior, high LC content, and a prolonged drug release. Therefore, the LC-loaded film may be considered a potential option to be applied as an alternative to treat dental pain.

Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders worldwide. It is caused by the degeneration of dopaminergic neurons from the substantia nigra pars compacta. This neuronal loss causes the dopamine deficiency that leads to a series of functional changes within the basal ganglia, producing motor control abnormalities. L-DOPA is considered the gold standard for PD treatment, and it may alleviate its clinical manifestations for some time. However, its prolonged administration produces tolerance and several severe side effects, including dyskinesias and gastrointestinal disorders. Thus, there is an urgent need to find effective medications, and current trends have proposed some natural products as emerging options for this purpose. Concerning this, curcumin represents a promising bioactive compound with high therapeutic potential. Diverse studies in cellular and animal models have suggested that curcumin could be employed for the treatment of PD. Therefore, the objective of this narrative mini-review is to present an overview of the possible therapeutic effects of curcumin and the subjacent molecular mechanisms. Moreover, we describe several possible nanocarrier-based approaches to improve the bioavailability of curcumin and enhance its biological activity.

Chalcones are among the leading bioactive flavonoids with a therapeutic potential implicated to an array of bioactivities investigated by a series of preclinical and clinical studies. In this article, different scientific databases were searched to retrieve studies depicting the biological activities of chalcones and their derivatives. This review comprehensively describes preclinical studies on chalcones and their derivatives describing their immense significance as antidiabetic, anticancer, anti-inflammatory, antimicrobial, antioxidant, antiparasitic, psychoactive, and neuroprotective agents. Besides, clinical trials revealed their use in the treatment of chronic venous insufficiency, skin conditions, and cancer. Bioavailability studies on chalcones and derivatives indicate possible hindrance and improvement in relation to its nutraceutical and pharmaceutical applications. Multifaceted and complex underlying mechanisms of chalcone actions demonstrated their ability to modulate a number of cancer cell lines, to inhibit a number of pathological microorganisms and parasites, and to control a number of signaling molecules and cascades related to disease modification. Clinical studies on chalcones revealed general absence of adverse effects besides reducing the clinical signs and symptoms with decent bioavailability. Further studies are needed to elucidate their structure activity, toxicity concerns, cellular basis of mode of action, and interactions with other molecules.

The use of natural polymers for the release of drugs is attractive due to biodegradability, biocompatibility, inexpensive, chemically modifiable, in addition to secondary properties such as high swelling capacity, bioadhesion, offering positive electric charges, and stimulus-sensitive factors such as pH and temperature. The present work proposes a critical approach to the state of the art on the applications of natural polymers for the release of drugs, and the manufacture of nanoparticles, including advantages and limitations. We also address the vectorization analysis of nanoparticles elaborated with natural polymers, and we emphasize the application of nanoparticles for gene therapy. Finally, due to the nature of nanoparticle fabrication and disposition, we included a section called “Special requirements in the characterization of excipients and nanoparticles fabricated with natural polymers” aimed to recommend a physicochemical characterization that guarantees the adequate reproducibility of the formulations, one of the great paradigms in the development of nanoparticles elaborated with natural polymers. Finally, we present a section denominated “Nanotoxicology of natural polymers used in the pharmaceutical area.” We mention specific cases of the limitations in this type of excipient, although we also highlight new and better properties that can be exploited.

In recent decades, interest in the Cordyceps genus has amplified due to its immunostimulatory potential. Cordyceps species, its extracts, and bioactive constituents have been related with cytokine production such as interleukin (IL)-1ß, IL-2, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor (TNF)-a, phagocytosis stimulation of immune cells, nitric oxide production by increasing inducible nitric oxide synthase activity, and stimulation of inflammatory response via mitogen-activated protein kinase pathway. Other pharmacological activities like antioxidant, anti-cancer, antihyperlipidemic, anti-diabetic, anti-fatigue, anti-aging, hypocholesterolemic, hypotensive, vasorelaxation, anti-depressant, aphrodisiac, and kidney protection, has been reported in pre-clinical studies. These biological activities are correlated with the bioactive compounds present in Cordyceps including nucleosides, sterols, flavonoids, cyclic peptides, phenolic, bioxanthracenes, polyketides, and alkaloids, being the cyclic peptides compounds the most studied. An organized review of the existing literature was executed by surveying several databanks like PubMed, Scopus, etc. using keywords like Cordyceps, cordycepin, immune system, immunostimulation, immunomodulatory, pharmacology, anti-cancer, anti-viral, clinical trials, ethnomedicine, pharmacology, phytochemical analysis, and different species names. This review collects and analyzes state-of-the-art about the properties of Cordyceps species along with ethnopharmacological properties, application in food, chemical compounds, extraction of bioactive compounds, and various pharmacological properties with a special focus on the stimulatory properties of immunity. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2020R1G1A1004667), Republic of Korea.

Human skin possesses an essential function in the maintenance of individuals' health. However, it may undergo a variety of lesions that produce wounds of distinct severity. In this respect, instantly after any skin wound, the process of tissue regeneration and repair initiates. Nevertheless, diverse factors can delay this process, including bacterial infections, nutritional status, age, hypoxia, chronic diseases, necrosis, and vascular and arterial diseases. Thus, wound dressings are frequently used to improve wound healing. Those wound dressings are fabricated with diverse materials, which confer them different properties. In this regard, hyaluronic acid is a natural polysaccharide widely distributed in extracellular matrices of mammal tissues, which possesses remarkable attributes in terms of biocompatibility, biodegradability, and low cost. Moreover, hyaluronic acid exhibits several beneficial effects on wound healing, such as the decrease of inflammatory processes, regulation of tissue remodeling, and enhancement of angiogenesis. Therefore, in recent years, there is growing attention in this polysaccharide for the design and manufacture of novel wound dressings, which have shown encouraging properties. Here, we describe the different approaches of hyaluronic acid for the production of wound dressings, encompassing hydrogels, films, scaffolds, foams, topical formulations, and nanoformulations, as well as its beneficial effects on wound healing. Finally, we discuss perspectives about the use of hyaluronic acid in wound dressings.

Controlled release is of vital relevance for many drugs; thus, there is a keen interest in materials that can improve the release profiles of formulations administered via buccal, transdermal, ophthalmic, vaginal, and nasal. The desirable effects of those materials include the improvement of stability, adhesiveness, solubility, and retention time. Hence, different synthetic and natural polymers are utilized to achieve these objectives. In this respect, xanthan gum is an anionic polysaccharide that can be obtained from Xanthomonas bacteria. It is a natural polymer broadly employed in numerous food products, lotions, shampoos, and dermatological articles. Furthermore, due to its physicochemical features, xanthan gum is growingly utilized for the development and improvement of drug delivery systems. In this regard, encouraging findings have been revealed by recent formulations for pharmaceutical applications, including antiviral carriers, antibacterial transporters, transdermal patches, vaginal formulations, and anticancer medications. In this article, we perform a concise description of the chemical properties of xanthan gum and its role as a modifier of drug release. Furthermore, we present an outlook of the state of the art of research focused on the utilization of xanthan gum in varied pharmaceutical formulations, which include tablets, films, hydrogels, and nanoformulations. Finally, we discuss some perspectives about the use of xanthan gum in these formulations.

Summary The Sc(III) MOF-type MFM-300(Sc) is demonstrated in this study to be stable under physiological conditions (PBS), biocompatible (to human skin cells), and an efficient drug carrier for the long-term controlled release (through human skin) of antioxidant ferulate. MFM-300(Sc) also preserves the antioxidant pharmacological effects of ferulate while enhancing the bio-preservation of dermal skin fibroblasts, during the delivery process. These discoveries pave the way toward the extended use of Sc(III)-based MOFs as drug delivery systems (DDSs)., Graphical Abstract, Highlights • MFM-300(Sc) presents good stability and biocompatibility • FER@MFM-300(Sc) allows the long-term transdermal release of ferulate (FER–) • FER@MFM-300(Sc) prevents the photodegradation of FER, Medicine; Chemistry; Inorganic Chemistry; Materials Structure

Sulfadiazine (SDZ), a bacteriostatic agent, was hosted in a metal–organic framework, specifically in MIL-53(Al) and modified-zinc MIL-53(Al,Zn). Materials were characterized structural, and texturally. Both hosts loaded sulfadiazine but they were differenced regarding the release of sulfadiazine. The presence of zinc plays a significant role to the modulation of sulfadiazine–MOF interactions. Release of sulfadiazine from sulfadiazine@MOFs was monitored in vitro and ex vivo conditions. A kinetic release model is proposed for in vitro sulfadiazine release. Remarkably, the materials did not show cytotoxicity against eukaryote cells.

This study aimed at investigating the synthesis, characterization, and search for a biotechnological application proposal for poly [(R)-3-hydroxybutyric acid] (PHB) grafted with the n-hydroxyethyl acrylamide (HEAA) monomer. The novel copolymer was prepared by 60Co gamma radiation-induced-graft polymerization. The effect of different solvents in the graft polymerization; the degree of grafting, crystallinity, and hydrophilicity; the morphology and the thermal properties were evaluated. The polyurethane fabricated from the grafted PHB was suggested as a scaffold. The enzymatic degradation behavior and the spectroscopic, morphological, mechanical, and biological properties of the composites were assessed. According to the results, the successful grafting of HEAA onto PHB was verified. The grafting was significantly affected by the type of solvent employed. A decreased crystallinity and increased hydrophilicity of the graft copolymer, concerning the PHB, was found. An increased roughness was observed in the morphology of the polymer after grafting. The thermodynamic parameters, except for the glass transition temperature, also decreased for the synthetic biopolymer. The intended use of these scaffolds for skin tissue engineering was supported by a proper degradability and degree of porosity, improved mechanical properties, the optimal culture of human fibroblasts, and its transfection with a plasmid vector containing an enhanced green fluorescent protein.

Dopamine D3 R are widely expressed in basal ganglia where interact with D1 R. D3 R potentiate cAMP accumulation and GABA release stimulated by D1 R in striatonigral neurons through "atypical" signaling. During dopaminergic denervation, D3 R signaling changes to a "typical" in which antagonizes the effects of D1 R, the mechanisms of this switching are unknown. D3 nf splice variant regulates membrane anchorage and function of D3 R and decreases in denervation; thus, it is possible that D3 R signaling switching correlates with changes in D3 nf expression and increases of membranal D3 R that mask D3 R atypical effects. We performed experiments in unilaterally 6-hydroxydopamine lesioned rats and found a decrease in mRNA and protein of D3 nf, but not of D3 R in the denervated striatum. Proximity ligation assay showed that D3 R-D3 nf interaction decreased after denervation, whereas binding revealed an increased Bmax in D3 R. The new D3 R antagonized cAMP accumulation and GABA release stimulated by D1 R; however, in the presence of N-Ethylmaleimide (NEM), to block Gi protein signaling, activation of D3 R produced its atypical signaling stimulating D1 R effects. Finally, we investigated if the typical and atypical effects of D3 R modulating GABA release are capable of influencing motor behavior. Injections of D3 R agonist into denervated nigra decreased D1 R agonist-induced turning behavior but potentiated it in the presence of NEM. Our data indicate the coexistence of D3 R typical and atypical signaling in striatonigral neurons during denervation that correlated with changes in the ratio of expression of D3 nf and D3 R isoforms. The coexistence of both atypical and typical signaling during denervation influences motor behavior.

Cardiovascular diseases (CVD) compromises a group of heart and blood vessels disorders with high impact on human health and wellbeing. Curcumin (CUR) have demonstrated beneficial effects on these group of diseases that represent a global burden with a prevalence that continues increasing progressively. Pre- and clinical studies have demonstrated the CUR effects in CVD through its anti-hypercholesterolemic and anti-atherosclerotic effects and its protective properties against cardiac ischemia and reperfusion. However, the CUR therapeutic limitation is its bioavailability. New CUR nanomedicine formulations are developed to solve this problem. The present article aims to discuss different studies and approaches looking into the promising role of nanotechnology-based drug delivery systems to deliver CUR and its derivatives in CVD treatment, with an emphasis on their formulation properties, experimental evidence, bioactivity, as well as challenges and opportunities in developing these systems. This work was supported by CONICYT PIA/APOYO CCTE AFB170007. N. Martins would like to thank the Portuguese Foundation for Science and Technology (FCT–Portugal) for the Strategic project ref. UID/BIM/04293/2013 and “NORTE2020—Programa Operacional Regional do Norte” (NORTE-01-0145-FEDER-000012).

Continuous changes in the needs of food consumption has focused on products that comply with functional properties and contain natural additives. In this chapter, important aspects for the formulation of nanoemulsions and other nanosized systems used as release systems of active substances are reviewed. We especially focus on natural substances, considering their manufacture, characterization, and compatibility with the food products, as well as their effects in the stabilization of food systems. Some important aspects include the compatibility of stabilizers and costabilizers utilized in the preparation of nanoemulsions and nanosized systems that can be loaded with the active substances employed as ingredients. There is an emphasis on their release, as well as the most appropriate release mechanisms according to the stage in which they must act during their manufacture and storage, and in relation to their effect on shelf life and physicochemical, textural, and sensorial properties.

The synthesis of novel degradable hydrogels, with designable structures and good biocompatibility, produces attractive materials for use in connective tissue regeneration applications. However, the way in which human fibroblast cells respond to terpolymer hydrogels such as collagen–polyvinylpyrrolidone–polyethylene glycol (C–PVP–PEG) remains largely unknown. The aim of this study was to synthesize a gamma-radiation-induced C–PVP–PEG hydrogel and to evaluate its structure, morphology and cell viability in fibroblasts. Fourier transform infrared spectroscopy showed shifting of amide I to higher frequencies, as evidence of crosslinking produced by the radiation. The morphology of the hydrogel varied with the ratio of the polymers. We show a proposal for the mechanism of the hydrogel synthesis. The in vitro assessment of the hydrogels suggested that at 50 kGy, the presence of collagen decreased the cell viability for all samples, except for C–PVP. However, when PEG and PVP were added to the collagen, the cell’s viability increased with respect to the irradiated collagen sample.

A novel brush-like poly(2-aminoethyl methacrylate) (PAEMA) was grafted onto chitosan (CS) through gamma radiation-induced polymerization. The copolymer (CS-g-PAEMA) was used to prepare a sodium acetate leached poly(urethane-urea) scaffold. The above derivatives were developed, synthesized, and characterized to meet the specific characteristics of biomaterials. The results revealed that this method is an easy and successful route for grafting PAEMA onto CS. The feasibility of preparing a CS-g-PAEMA polyurethane foam was confirmed by mechanical, morphometric, spectroscopic, and cytotoxic studies. The scaffold showed high biocompatibility both in vitro and in vivo. The first experiment proved that CS-based polyurethane efficiently allows the dynamic culturing of human fibroblast cells. Additionally, an in vivo study in a murine model indicated a complete integration of the scaffold to surrounding subcutaneous tissue as supported by the histological and histochemical assessments. The aforementioned results support the use of CS-g-PAEMA poly(saccharide-urethane) as a model of in vitro-engineered skin.

CB2 receptors (CB2 R) are expressed in midbrain neurons. To evidence the control of dopamine release in dorsal striatum by CB2 R, we performed experiments of [3 H]-dopamine release in dorsal striatal slices. We found a paradoxical increase in K+ -induced [3 H]-dopamine release by CB2 R activation with GW 833972A and JWH 133 two selective agonist. To understand the mechanism involved, we tested for a role of the D2 autoreceptor in this effect; because in pallidal structures, the inhibitory effect of CB1 receptors (CB1 R) on GABA release is switched to a stimulatory effect by D2 receptors (D2 R). We found that the blockade of D2 autoreceptors with sulpiride prevented the stimulatory effect of CB2 R activation; in fact, under this condition, CB2 R decreased dopamine release, indicating the role of the D2 autoreceptor in the paradoxical increase. We also found that the effect occurs in nigrostriatal terminals, since lesions with 6-OH dopamine in the middle forebrain bundle prevented CB2 R effects on release. In addition, D2 -CB2 R interaction promoted cAMP accumulation, and the increase in [3 H]-dopamine release was prevented by PKA blockade. D2 -CB2 R coprecipitation and proximity ligation assay studies indicated a close interaction of receptors that could participate in the observed effects. Finally, intrastriatal injection of CB2 R agonist induced contralateral turning in amphetamine-treated rats, which was prevented by sulpiride, indicating the role of the interaction in motor behavior. Thus, these data indicate that the D2 autoreceptor switches, from inhibitory to stimulatory, the CB2 R effects on dopamine release, involving the cAMP → PKA pathway in nigrostriatal terminals.

In vivo activation of dopamine D3 receptors (D3Rs) depresses motor activity. D3Rs are widely expressed in subthalamic, striatal, and dendritic dopaminergic inputs into the substantia nigra pars reticulata (SNr). In vitro studies showed that nigral D3Rs modulate their neurotransmitter release, thus, it could be that these changes in neurotransmitter levels modify the discharge of nigro-thalamic neurons and, therefore, motor behavior. To determine how the in vitro responses correspond to the in vivo responses, we examined the effect of intra-nigral and systemic blockade of D3Rs in the interstitial content of glutamate, dopamine, and GABA within the SNr using microdialysis coupled to motor activity determinations in freely moving rats. Intranigral unilateral blockade of D3R with GR 103,691 increased glutamate, dopamine, and GABA. Increments correlated with increased ambulatory distance, non-ambulatory activity, and induced contralateral turning. Concomitant blockade of D3R with D1R by perfusion of SCH 23390 reduced the increase of glutamate, prevented the increment of GABA, but not of dopamine, and abolished behavioral effects. Glutamate stimulates dopamine release by NMDA receptors, while blockade with kynurenic acid prevented the increase in dopamine and, in turn, of GABA and glutamate. Finally, systemic administration of D3R selective antagonist U 99194A increased glutamate, dopamine, and GABA in SNr and stimulated motor activity. Blockade of intra-nigral D1R with SCH 23390 prior to systemic U 99194A diminished increases in neurotransmitter levels and locomotor activity. These data highlight the pivotal role of presynaptic nigral D3 and D1R in the control of motor activity and help to explain part of the effects of the in vivo administration of D3R agents.

Curcumin is a polyphenol that is obtained from Curcuma longa and used in various areas, such as food and textiles. Curcumin has important anti-inflammatory and antioxidant properties that allow it to be applied as treatment for several emerging pathologies. Remarkably, there are an elevated number of publications deriving from the terms “curcumin„ and “curcumin brain diseases„, which highlights the increasing impact of this polyphenol and the high number of study groups investigating their therapeutic actions. However, its lack of solubility in aqueous media, as well as its poor bioavailability in biological systems, represent limiting factors for its successful application. In this review article, the analysis of its chemical composition and the pivotal mechanisms for brain applications are addressed in a global manner. Furthermore, we emphasize the use of nanoparticles with curcumin and the benefits that have been reached as an example of the extensive advances in this area of health.

This work aims to study the bio-interfacial properties of poly(ester-urethane) composite scaffolds based on poly (3-hydroxybutyrate) [PHB] and modified by surface plasma-radiation-induced graft polymerization of N-isopropylacrylamide (NIPAAm). The delivering power of the Argon radio-frequency plasma was increased from 5−20 W. The yields over the polyurethane surface, grafting density, topographical dimensions, architecture, surface energy, and wettability were surveyed in the established plasma regimes. Successful grafting of NIPAAm was verified by Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy analysis. Characterization using atomic force microscopy revealed that the surface of the scaffolds is more uniform in lower plasma delivering powers. The results show a high grafting density surface with a low degree of grafting (3–9 %). The contact angles decreased, and the surface energy rose with increasing delivering power. The surface area, total pore volumes are similar between the samples. The porosity percentage and the average pore diameter hinted at a decrease in the treated composite as compared to the pristine scaffold. Although all the composites showed to be non-toxic and highly viable (>98 %) for human dermal fibroblasts, the results showed better attachment, spreading, and growth of fibroblasts on scaffolds with moderate hydrophilicity (5 W). The in vivo experiments revealed that the plasma-treated scaffolds diminished the inflammatory infiltrate, which means an improved acceptance as compared with untreated PHB polyurethane.

Chitosan is a natural polymer extensively applied in the cosmetic, textile, food, and agricultural industries. Chitosan possesses biocompatibility, biodegradability, and antibacterial activity; thus, it is employed for a variety of biomedical applications. Furthermore, due to its ability to modify the physicochemical features of preformed nanoparticles, numerous research groups have exploited the coating of nanoparticles with chitosan to obtain new biological properties. In this regard, the decoration with chitosan confers the exposure of electro-charged amino groups towards the surface of nanoparticles, which is evidenced by positive zeta potentials. Although other biomaterials may provide a positive zeta potential, these involve low robust production methods, whereas chitosan-decorated nanoparticles may be obtained by straightforward ionic gelation techniques. Concerning this, methods of physical adsorption are the most employed because they involve a short time and low resources. However, the coating of nanoparticles through cross-linking with chitosan represents an exciting option. In this article, we perform a description of the structure and physicochemical chitosan properties. Moreover, we describe different strategies for coating with chitosan the surface of distinct types of nanoparticles and the subsequent changes in their biological and physicochemical properties. Finally, we mention several biomedical applications of these chitosan-decorated nanoparticles and discuss future perspectives.

The blood-brain barrier (BBB) is a sophisticated and very selective dynamic interface composed of endothelial cells expressing enzymes, transport systems, and receptors that regulate the passage of nutrients, ions, oxygen, and other essential molecules to the brain, regulating its homeostasis. Moreover, the BBB performs a vital function in protecting the brain from pathogens and other dangerous agents in the blood circulation. Despite its crucial role, this barrier represents a difficult obstacle for the treatment of brain diseases because many therapeutic agents cannot cross it. Thus, different strategies based on nanoparticles have been explored in recent years. Concerning this, chitosan-decorated nanoparticles have demonstrated enormous potential for drug delivery across the BBB and treatment of Alzheimer’s disease, Parkinson’s disease, gliomas, cerebral ischemia, and schizophrenia. Our main objective was to highlight the high potential of chitosan adsorption to improve the penetrability through the BBB of nanoformulations for diseases of CNS. Therefore, we describe the BBB structure and function, as well as the routes of chitosan for crossing it. Moreover, we define the methods of decoration of nanoparticles with chitosan and provide numerous examples of their potential utilization in a variety of brain diseases. Lastly, we discuss future directions, mentioning the need for extensive characterization of proposed nanoformulations and clinical trials for evaluation of their efficacy.

The synthesis of the poly(ester-urethanes) using poly(3-hydroxybutyrate) has gained increasing interest as scaffolds for use in tissue engineering despite their moderate hydrophobicity and biocompatibility. However, it is not yet known if the grafting of poly(N‐hydroxyethyl acrylamide) is suitable to improve the degree of hydrophilicity of the surface. This study aims to tailor the surface of these biopolymers by plasma-induced graft polymerization of N‐hydroxyethyl acrylamide. The synthesized specimens are characterized by Fourier-transform infrared spectroscopy, scanning electron microscope, atomic force microscope, and contact angle measurements. The cell viability and cytotoxicity of the samples are assessed through MTT and live/dead viability/cytotoxicity kit assays with pancreatic islet cells. Our findings suggest that the plasma-induced surface grafting increase the roughness and the wettability, and also improve the cell viability of the starting substrate.

The sterilization processes of nanoparticles (NP) by autoclaving and filtration are two of the most utilized methods in the pharmaceutical industry but are not always a viable option. For this reason, the search for alternative options such as UV and gamma radiation is of interest. In this work, we evaluated both types of sterilization on two types of NP in solid state widely employed in the literature for biomedical applications, poly-(&epsilon, caprolactone) and poly(D, L-lactide-co-glycolide) acid NP stabilized with polyvinyl alcohol. Physicochemical properties and cell viability were studied pre- and post-sterilization. The efficiency of irradiation sterilization was performed by a test of sterility using 1 &times, 108 CFU/mL of Escherichia coli, Staphylococcus aureus, and Candida albicans. Microbiological monitoring revealed that both methods were sufficient for sterilization. After the UV irradiation sterilization (100 &micro, J/cm2), no substantial changes were observed in the physicochemical properties of the NP or in the interaction or morphology of human glial cells, though 5 and 10 kGy of gamma irradiation showed slight changes of NP size as well as a decrease in cell viability (from 100 &micro, g/mL of NP). At 5 kGy of radiation doses, the presence of trehalose as cryoprotectant reduces the cell damage with high concentrations of NP, but this did not occur at 10 kGy. Therefore, these methods could be highly effective and low-processing-time options for sterilizing NP for medical purposes. However, we suggest validating each NP system because these generally are of different polymer-composition systems.

The use of poly(ethylene glycol) (PEG) for the development of novel PEGylated biomolecules is playing an increasingly meaningful role in cancer treatment. Cisplatin (CDDP), is a useful chemotherapy drug. However, it is unclear whether PEGylated cisplatin (CDDPPEG) has potential as an alternative therapeutic agent. Here we prepared a PEGylated cisplatin by gamma radiation-induced synthesis, for the first time. PEGylated drugs were characterized using Raman and Fourier transform infrared spectroscopy (FTIR), as well as scanning electron microscopy coupled with Energy Dispersive X-ray (SEM/EDX). The results show that the cisplatin can be successfully PEGylated by this method. Furthermore, we show a proposal for the mechanism of the PEGylation reaction. The novel product exhibits in vitro therapeutic potential comparable to cisplatin at concentrations lower than 23 μM (Pt), causing differences in cell cycle checkpoints, which suggest changes in the signaling pathways that control growth arrest and cause apoptosis of A549 cells.

Collagen-polyvinylpyrrolidone (C-PVP) is a copolymer that is generated from the γ irradiation of a mixture of type I collagen and low-molecular-weight PVP. It is characterized by immunomodulatory, fibrolytic, and antifibrotic properties. Here, we used various physicochemical and biological strategies to characterize the structure, biochemical susceptibility, as well as its effects on metabolic activity in fibroblasts. C-PVP contained 16 times more PVP than collagen, but only 55.8% of PVP was bonded. Nevertheless, the remaining PVP exerted strong structural activity due to the existence of weak bonds that provided shielding in the NMR spectra. On SEM and AFM, freeze-dried C-PVP appeared as a film that uniformly covered the collagen fibers. Size analysis revealed the presence of abundant PVP molecules in the solution of the copolymer with a unique dimension related to macromolecular combinations. Calorimetric analysis showed that the copolymer in solution exhibited structural changes at 110 °C, whereas the lyophilized form showed such changes at temperatures below 50 °C. The copolymer presented a rheopectic behavior, with a predominant effect of the collagen. C-PVP had biological effects on the expression of integrin α2 and prolyl-hydroxylase but did not interact with cells through the collagen receptors because it did not inhibit or slow contraction.

This work aimed to develop and evaluate pH-dependent systems based on nanospheres (NSphs) and nanocapsules (NCs) loaded with chlorhexidine (CHX) base as a novel formulation for the treatment of periodontal disease. Cellulose acetate phthalate (CAP) was employed as a pH-dependent polymeric material. The NSphs and NCs were prepared using the emulsion-diffusion technique and then characterized according to encapsulation efficiency (EE), size, zeta-potential, morphology, thermal properties, release profiles and a preliminary clinical panel test. The formulations showed 77% and 61% EE and 57% and 84% process efficiency (PE), respectively. Both systems were spherical with an average size of 250&ndash, 300 nm. Differential scanning calorimetry (DSC) studies showed that the drug has the potential to be dispersed molecularly in the NSph matrix or dissolved in the oily center of the NCs. The CHX release test revealed that the release of NSphs-CHX follows Fickian diffusion involving diffusion-erosion processes. The NCs showed a slower release than the NSphs, following non-Fickian diffusion, which is indicative of anomalous transport. These nanosystems may, therefore, be employed as novel formulations for treating periodontal disease, due to (1) their coverage of a large surface area, (2) the controlled release of active substances at different pH, and (3) potential gingival tissue infiltration.

Non-biodegradable materials with a low swelling capacity and which are opaque and occlusive are the main problems associated with the clinical performance of some commercially available wound dressings. In this work, a novel biodegradable wound dressing was developed by means of alginate membrane and polycaprolactone nanoparticles loaded with curcumin for potential use in wound healing. Curcumin was employed as a model drug due to its important properties in wound healing, including antimicrobial, antifungal, and anti-inflammatory effects. To determine the potential use of wound dressing, in vitro, ex vivo, and in vivo studies were carried out. The novel membrane exhibited the diverse functional characteristics required to perform as a substitute for synthetic skin, such as a high capacity for swelling and adherence to the skin, evidence of pores to regulate the loss of transepidermal water, transparency for monitoring the wound, and drug-controlled release by the incorporation of nanoparticles. The incorporation of the nanocarriers aids the drug in permeating into different skin layers, solving the solubility problems of curcumin. The clinical application of this system would cover extensive areas of mixed first- and second-degree wounds, without the need for removal, thus decreasing the patient&rsquo, s discomfort and the risk of altering the formation of the new epithelium.

Ferulic acid anions were intercalated in a Zn–Al layered double hydroxide. The materials generated by this process were characterised structurally and tested in two important applications: as in vitro drug delivery agents in a system that mimics biological conditions, for which a mathematical model describing the drug delivery profile was created, and as antioxidants for human fibroblasts.

Application of polymers cross-linked by gamma irradiation on cutaneous wounds has resulted in the improvement of healing. Chitosan (CH) and poloxamer 407 (P407)-based hydrogels confer different advantages in wound management. To combine the properties of both compounds, a gamma-irradiated mixture of 0.75/25% (w/w) CH and P407, respectively, was obtained (CH-P), and several physical, chemical, and biological analyses were performed. Notably, gamma radiation induced changes in the mixture's thermal behavior, viscosity, and swelling, and exhibited stability at neutral pH. The thermal reversibility provided by P407 and the bacteriostatic effect of CH were maintained. Mice full-thickness wounds treated with CH-P diminished the wound area during the first days. Consequently, with this treatment, increased levels of macrophages, α-SMA, and collagen deposition in wounds were observed, indicating a more mature scar tissue. In conclusion, the new hydrogel CH-P, at physiologic pH, combined the beneficial characteristics of both polymers and produced new properties for wound management.

The purpose of this work was to propose a drug delivery system based on a biodegradable porous membrane, whose surface is covered by a nanoparticle film, thus achieving a controlled drug release rate. Furthermore, due to the fact that the assembly of the system is performed in aqueous medium, contact with organic solvents is avoided. The method is performed in two steps: (i) preparation of biodegradable porous membranes (by a solvent casting and particulate leaching technique) and biodegradable nanoparticles (by the emulsification-diffusion method), extensively eliminating the solvent in both of them; (ii) infiltration into membranes of an aqueous solution of a model drug (carbamazepine) and a nanoparticle dispersion. In both cases, poly(DL-lactic-co-glycolic acid) (PLGA 50:50) was used as a biodegradable polymer. Carbamazepine adsorbed onto biodegradable porous membranes shows an immediate release behavior (95% released in