Synthesis of sericin-based conjugates by click chemistry: enhancement of sunitinib bioavailability and cell membrane permeation

Sericin is a natural protein that has been used in biomedical and pharmaceutical fields as raw material for polypeptide-based drug delivery systems (DDSs). In this paper, it has been employed as pharmaceutical biopolymer for the production of sunitinib–polypeptide conjugate. The synthesis has been carried out by simple click reaction in water, using the redox couple l-ascorbic acid/hydrogen peroxide as a free radical grafting initiator. The bioconjugate molecular weight (50 kDa < Mw < 75 kDa) was obtained by SDS-PAGE, while the spectroscopic characteristics have been studied in order to reveal the presence of grafted sunitinib. In both FT-IR and UV/Vis spectra, signals corresponding to sunitinib functional groups have been identified. Since sunitinib is an anticancer drug characterized by low bioavailability and low permeability, the bioconjugation aimed at their enhancement. In vitro studies demonstrated that bioavailability has been increased to almost 74%, compared with commercial formulation. Also cell membrane permeability has been augmented in in vitro tests, in which membrane models have been used to determine the lipid membrane/physiological fluid partition coefficient (Kp). The log(Kp) value of the bioconjugate was increased to over 4. This effect resulted in a three-fold decrease of IC50 value against MCF-7 cells

Quercetin derivatives as novel antihypertensive agents: Synthesis and physiological characterization

The antihypertensive flavonol quercetin (Q1) is endowedwith a cardioprotective effect againstmyocardial ischemic damage. Q1 inhibits angiotensin converting enzymeactivity, improves vascular relaxation, and decreases oxidative stress and gene expression. However, the clinical application of this flavonol is limited by its poor bioavailability and low stability in aqueous medium. In the aimto overcome these drawbacks and preserve the cardioprotective effects of quercetin, the present study reports on the preparation of five different Q1 analogs, in which all OH groups were replaced by hydrophobic functional moieties. Q1 derivatives have been synthesized by optimizing previously reported procedures and analyzed by spectroscopic analysis. The cardiovascular properties of the obtained compounds were also investigated in order to evaluate whether chemical modification affects their biological efficacy. The interaction with β-adrenergic receptors was evaluated by molecular docking and the cardiovascular efficacy was investigated on the ex vivo Langendorff perfused rat heart. Furthermore, the bioavailability and the antihypertensive properties of the most active derivative were evaluated by in vitro studies and in vivo administration (1month) on spontaneously hypertensive rats (SHRs), respectively. Among all studied Q1 derivatives, only the ethyl derivative reduced left ventricular pressure (at 10−8M÷10−6Mdoses) and improved relaxation and coronary dilation. NOSs inhibition by L-NAME abolished inotropism, lusitropism and coronary effects. Chronic administration of high doses of this compound on SHR reduced systolic and diastolic pressure. Differently, the acetyl derivative induced negative inotropism and lusitropism (at 10−10M and 10−8 ÷ 10−6 M doses), without affecting coronary pressure. Accordingly, docking studies suggested that these compounds bind both β1/β2-adrenergic receptors. Taking into consideration all the obtained results, the replacement of OHwith ethyl groups seems to improve Q1 bioavailability and stability; therefore, the ethyl derivative could represent a good candidate for clinical use in hypertension

Parathyroidectomy and survival in a cohort of Italian dialysis patients: results of a multicenter, observational, prospective study

Background: Severe secondary hyperparathyroidism (SHPT)&nbsp;is associated with mortality in end stage kidney disease (ESKD). Parathyroidectomy (PTX) becomes necessary when medical therapy fails, thus highlighting the interest to compare biochemical and clinical outcomes of patients receiving either medical treatment or surgery. Methods: We aimed to compare overall survival and biochemical control of hemodialysis patients with severe hyperparathyroidism, treated by surgery or medical&nbsp;therapy&nbsp;followed-up for 36&nbsp;months.&nbsp;Inclusion criteria were age older than 18&nbsp;years, renal failure requiring dialysis treatment (hemodialysis or peritoneal dialysis) and ability to sign the consent form. A control group of&nbsp;418 patients treated in the same centers,&nbsp;who did not undergo parathyroidectomy was selected after matching&nbsp;for&nbsp;age, sex, and dialysis vintage. Results: From 82 Dialysis units in Italy, we prospectively collected data of 257 prevalent patients&nbsp;who underwent parathyroidectomy (age&nbsp;58.2 ± 12.8 years; M/F: 44%/56%, dialysis&nbsp;vintage: 15.5 ± 8.4 years) and of 418 control patients who did not undergo parathyroidectomy (age&nbsp;60.3 ± 14.4 years; M/F 44%/56%; dialysis vintage 11.2 ± 7.6 y). The survival rate was higher in the group&nbsp;that underwent&nbsp;parathyroidectomy (Kaplan–Meier log rank test = 0.002). Univariable analysis (HR 0.556, CI: 0.387–0.800, p = 0.002) and multivariable analysis (HR 0.671, CI:0.465–0.970, p = 0.034), identified parathyroidectomy as a&nbsp;protective factor of overall survival. The prevalence of patients at KDOQI targets for PTH was lower in patients&nbsp;who underwent parathyroidectomy&nbsp;compared to controls (PTX vs non-PTX: PTH &lt; 150&nbsp;pg/ml: 59% vs 21%, p = 0.001; PTH at target: 18% vs 37% p = 0.001; PTH &gt; 300&nbsp;pg/ml 23% vs 42% p = 0.001). The control group received more intensive medical treatment&nbsp;with higher prevalence of vitamin D (65% vs 41%, p = 0.0001), calcimimetics (34% vs 14%, p = 0.0001) and phosphate binders (77% vs 66%,&nbsp;p = 0.002). Conclusions: Our data suggest that parathyroidectomy is associated with survival rate&nbsp;at 36 months, independently of biochemical control. Lower exposure to high PTH levels could represent an advantage in the long term. Graphical abstract: [Figure not available: see fulltext.]

Polymer-based drug delivery systems: a study on micro and nanoparticles as carriers for bioactive molecules

Dottorato di Ricerca in Life Sciencesf. Ciclo XXXIThe works presented in this book are the result of the research carried out by the candidate, Luca Scrivano, during his 3 years Ph.D. at the Department of Pharmacy, Health and Nutritional Sciences of the University of Calabria (IT). His research was focused on the development of polymeric materials for the preparation of nanosized and micrometric drug delivery systems. Many strategies were explored and four different categories of polymeric particles were investigated: molecularly imprinted polymers, polymer-drug conjugates, polymeric vesicles and polymeric micelles. Both natural and synthetic polymers were employed for the development of these particles. The thesis is dived in two sections: Part I is focused on molecularly imprinted polymers (MIPs) as drug delivery systems. After a brief introduction about molecular imprinting technology in Chapter 1, the classic approach for the synthesis of MIPs for the delivery and release of an anticancer drug, namely sunitinib, is reported in Chapter 2. In Chapter 3, instead, a novel strategy for the synthesis of molecularly imprinted microrods through mesophase polymerization is presented. Finally, the use of diclofenac imprinted polymers for the production of hybrid smart bandages is described in Chapter 4. Part II is focused on nanosystems for the delivery of poorly water soluble drugs. Three different systems are presented in this section (and a short introduction is given in Chapter 5): a polymer-drug conjugate, a polymeric vesicle and polymeric micelles. For the polymer-drug conjugate reported in Chapter 6, sericin was used as starting material and sunitinib as drug substance. To achieve the final product, a click chemistry approach was applied, based on free radical grafting in aqueous solution. Oleate functionalization of dextran, described in Chapter 7, was carried out to prepare self-assembled polymeric vesicles, for the delivery a new antibacterial agent, synthesized by the group of medicinal chemistry of the Department of Pharmacy, Health and Nutritional Sciences of University of Calabria. Research on polymeric micelles for the targeted delivery of a photosensitizer for application in photodynamic therapy, reported in Chapter 8, was carried out at the Department of Pharmaceutical Sciences of Utrecht University (NL), under the supervision of Prof. Wim Hennink, Dr. Cornelus F. van Nostrum and Dr. Sabrina Oliveira, during the last seven months of the Ph.D. course. In the attempt to explore the wide world of the drug delivery systems, polymeric carriers were chosen exclusively for the investigation carried out by the candidate. Among them, only the systems which may offer great advantages, such as stability, controlled release, high loading capacity and improved solubility of hydrophobic drugs, were selected. But alongside with the advantages are the disadvantages: in the Conclusions is, indeed, reported that all the good qualities can never be found in only one system and that the selection of the polymeric carrier must be done carefully, by taking into account the physical-chemical properties of the drug and the physio-pathological characteristics of the diseased tissue, target site of the bioactive compoundsUniversità degli Studi della Calabri

Smart Bandage Based on Molecularly Imprinted Polymers (MIPs) for Diclofenac Controlled Release

The aim of the present study was the development of a “smart bandage” for the topical administration of diclofenac, in the treatment of localized painful and inflammatory conditions, incorporating Molecularly Imprinted Polymers (MIPs) for the controlled release of this anti-inflammatory drug. For this purpose, MIP spherical particles were synthesized by precipitation polymerization, loaded with the therapeutic agent and incorporated into the bandage surface. Batch adsorption binding studies were performed to investigate the adsorption isotherms and kinetics and the selective recognition abilities of the synthesized MIP. In vitro diffusion studies were also carried out using Franz cells and the obtained results were reported as percentage of the diffused dose, cumulative amount of diffused drug, steady-state drug flux and permeability coefficient. Moreover, the biocompatibility of the developed device was evaluated using the EPISKIN™ model. The Scatchard analysis indicated that the prepared MIP is characterized by the presence of specific binding sites for diclofenac, which are not present in the corresponding non-imprinted polymer, and the obtained results confirmed both the ability of the prepared bandage to prolong the drug release and the absence of skin irritation reactions. Therefore, these results support the potential application of the developed “smart bandage” as topical device for diclofenac sustained release

Smart Bandage Based on Molecularly Imprinted Polymers (MIPs) for Diclofenac Controlled Release

The aim of the present study was the development of a &ldquo;smart bandage&rdquo; for the topical administration of diclofenac, in the treatment of localized painful and inflammatory conditions, incorporating Molecularly Imprinted Polymers (MIPs) for the controlled release of this anti-inflammatory drug. For this purpose, MIP spherical particles were synthesized by precipitation polymerization, loaded with the therapeutic agent and incorporated into the bandage surface. Batch adsorption binding studies were performed to investigate the adsorption isotherms and kinetics and the selective recognition abilities of the synthesized MIP. In vitro diffusion studies were also carried out using Franz cells and the obtained results were reported as percentage of the diffused dose, cumulative amount of diffused drug, steady-state drug flux and permeability coefficient. Moreover, the biocompatibility of the developed device was evaluated using the EPISKIN&trade; model. The Scatchard analysis indicated that the prepared MIP is characterized by the presence of specific binding sites for diclofenac, which are not present in the corresponding non-imprinted polymer, and the obtained results confirmed both the ability of the prepared bandage to prolong the drug release and the absence of skin irritation reactions. Therefore, these results support the potential application of the developed &ldquo;smart bandage&rdquo; as topical device for diclofenac sustained release

Molecularly Imprinted Microrods via Mesophase Polymerization

The aim of the present research work was the synthesis of molecularly imprinted polymers (MIPs) with a rod-like geometry via “mesophase polymerization”. The ternary lyotropic system consisting of sodium dodecyl sulfate (SDS), water, and decanol was chosen to prepare a hexagonal mesophase to direct the morphology of the synthesized imprinted polymers using theophylline, methacrylic acid, and ethylene glycol dimethacrylate as a drug model template, a functional monomer, and a crosslinker, respectively. The obtained molecularly imprinted microrods (MIMs) were assessed by performing binding experiments and in vitro release studies, and the obtained results highlighted good selective recognition abilities and sustained release properties. In conclusion, the adopted synthetic strategy involving a lyotropic mesophase system allows for the preparation of effective MIPs characterized by a rod-like morphology

A study on photostability of amphetamines and ketamine in hair irradiated under artificial sunlight

Drugs incorporated into hair are exposed to the environment, and cosmetic and chemical treatments, with possible decreases in their content. Knowledge concerning the effect of sunlight on drug content in hair can be helpful to forensic toxicologists, in particular, when investigating drug concentrations above or below pre-determined cut-offs. Twenty authentic positive hair samples were selected which had previously tested positive for amphetamines and/or ketamine. Washed hair were divided into two identical strands, with the former exposed at 765 W/m\ub2 (300\u207b800 nm spectrum of irradiance) for 48 h in a solar simulator, and the latter kept in the dark. Hair samples were extracted and analyzed by liquid chromatography high-resolution mass spectrometry detection. The percentage of photodegradation was calculated for each analyte (i.e., amphetamine, methamphetamine, methylendioxyamphetamine, ketamine, and norketamine). In parallel, photodegradation processes of standard molecules dissolved in aqueous and organic solutions were studied. In 20 hair samples positive for the targeted analytes, exposure to artificial sunlight induced an appreciable decrease in drug concentrations. The concentration ranges in the non-irradiated hair samples were 0.01\u207b24 ng/mg, and 65% of samples exhibited a decrease in post-irradiation samples, with reduction from 3% to 100%. When more drugs were present in the same hair sample (i.e., MDMA and ketamine) the degradation yields were compound dependent. A degradation product induced by irradiation of ketamine in aqueous and methanol solutions was identified; it was also found to be present in a true positive hair sample after irradiation. Ketamine, amphetamines, and their metabolites incorporated in the hair of drug users undergo degradation when irradiated by artificial sunlight. Only for ketamine was a photoproduct identified in irradiated standard solutions and in true positive irradiated hair. When decisional cut-offs are applied to hair analysis, photodegradation must be taken into account since sunlight may produce false negative results. Moreover, new markers could be investigated as evidence of illicit drug use

Recent Changes in Drug Abuse Scenario The Novel Psychoactive Substances (NPS) Phenomenon

Over the last decade, the emergence of a vast range of new/novel/emerging psychoactive substances (NPS) has progressively changed drug market scenarios, which have shifted from the ‘street’ to a ‘virtual’/online environment. Several definitions of NPS are in use, with the term ‘new’ not necessarily referring to new inventions but to substances that have recently been made available, possibly including failed pharmaceuticals or old patents which have been ‘rediscovered’ as ‘recreational’ molecules. Conversely, the term ‘novel’ can refer to something newly created, an old drug that has come back into fashion, or a known NPS molecule being used in an innovative or unusual way and hence presenting a ‘novelty’ appeal (Corkery et al., 2018) [1]. Though misleading, the terms ‘legal highs’ and ‘research chemicals’ have been used alternately to describe these molecules. NPS includes synthetic cannabinoids, cathinone derivatives, psychedelic phenethylamines, novel stimulants, synthetic opioids, tryptamine derivatives, phencyclidine-like dissociatives, piperazines, GABA-A/B receptor agonists, a range of prescribed medications, psychoactive plants/herbs, and a large series of image- and performance-enhancing drugs (IPED) (Schifano et al., 2015) [2]. Overall, users are typically attracted to NPS because of curiosity and the diffusion of social media users’ experiences, easy availability or affordability from online drug shops, legality, intense psychoactive effects, and the likely lack of detection in routine drug screenings (Schifano et al., 2015) [2]. Between 2004 and 2017, some 700–800 examples of NPS were reported by related European and international drug agencies (UNODC, 2018 [3]; EMCDDA, 2018 [4]), with most molecules identified being synthetic cannabinoids, synthetic cathinones, phenethylamine derivatives, and synthetic opioids. However, it could be argued that the NPS scenario is much larger than that outlined by those molecules which have been seized or formally identified by EU and international agencies. Since the online NPS scenario typically predicts the real life NPS scenario (Schifano et al., 2015) [2], identifying what is being discussed online by web-based NPS enthusiasts, or ‘e-psychonauts’ (Orsolini et al., 2015) [5], may well be of interest. With this in mind, a crawling/navigating software (i.e., the ‘NPS.Finder®’) was recently designed by our group. In November 2017, it started to automatically scan, on a 24/7 basis, a vast range of psychonaut web forums for NPS. After a year of operation, it has been possible to estimate that the online/psychonaut web forum NPS scene may include some 4000 different molecules. The most popular examples of NPS mentioned in psychonaut forums have included synthetic cannabimimetics, synthetic opioids, phenethylamines, designer benzodiazepines, and prescribed drugs. NPS use, especially for synthetic cannabinoids and novel psychedelics, has been associated with a range of untoward medical consequences, including vomiting, seizures, cardiovascular complications, and kidney failure (Schifano et al., 2017) [6]. By contrast, the main focus of this special issue is on the major psychopathological consequences of NPS use. Indeed, due to their complex pharmacodynamics, there are increasing levels of concern about the onset of acute or chronic psychopathological issues associated with NPS intake. Brain Sci. 2018, 8, 221; doi:10.3390/brainsci8120221 1 www.mdpi.com/journal/brainsci Brain Sci. 2018, 8, 221 The occurrence of psychosis has been related to: (a) increased central dopamine levels, typically seen with novel psychedelic phenethylamines, novel stimulants and synthetic cathinones; (b) significant cannabinoid CB1 receptor activation, which is associated with high potency synthetic cannabimimetics; (c) 5-HT2A receptor activation, seen with latest generation phenethylamines, tryptamine derivatives and hallucinogenic plants; (d) antagonist activity at n-methyl-D-aspartate/NMDA receptors, observed with ketamine, methoxetamine/MXE, and their latest derivatives; and (e) k-opioid receptor activation, which is typically associated with both Salvia divinorum and Mitragyna speciosa/‘Kratom’ intake. By considering the above, this special issue of Brain Sciences aims to provide an overview of a range of NPS-related issues. More precisely, Sahai et al. [7] present original preclinical data relating in silico and in vitro assessment of the psychoactive properties of a few dissociative diarylethylamines. Miolo et al. [8] focus on specific analytical chemistry issues relating to amphetamine-type stimulants and ketamine, while Parrott [9] argues that there are similarities between well-known recreational drugs and NPS in terms of mood fluctuations/psychobiological instability issues. Conversely, Cohen andWeinstein [10] present original cognitive psychopharmacology data relating to the use of organic and synthetic cannabinoids. From a clinical point of view, Bonaccorso et al. [11] introduce a case series of synthetic cannabinoid users presenting to acute psychiatric services with psychosis; Frisoni et al. [12] comment on the medical consequences of novel opioid intake; Martinotti et al. [13] provide a thorough overview of hallucinogen-persisting perceptual disorder, a clear issue of interest for NPS users; Schifano et al. [14] reflect on the misuse and abuse of prescribed medicines (e.g., benzodiazepine derivatives, methylphenidate look-alikes, and fentanyl analogues) in the NPS context; and Gittins et al. [15] provide empirical data relating NPS use by clients seeking treatment in the UK. BothWadsworth et al. [16] and Miliano et al. [17] comment extensively on the role of the open/deep web in shaping and promoting changes in NPS scenarios. Finally, both Metastasio et al. [18] and Catalani et al. [19] offer original data which sheds further light on the expanding phenomenon of IPED misuse/abuse. In conjunction with constant changes in basic structures from which emerging molecules can be derived, designed, and synthesized, the NPS market will continue to expand. This will pose a challenge, since NPS-related toxidromes are, per se, complex and unpredictable, and clinicians need to aim to be better educated in recognizing NPS-related toxicity issues. Drug control policies should be improved worldwide, and the list of examples of NPS should be constantly updated as improvements in analytical chemistry detection methods occur. Given the implications of NPS for mental health, psychiatric services should adapt to new drug scenarios while drafting new treatment strategies. Conflicts of Interest: The author declares no conflict of interest. References 1. ReadCorkery, J.M.; Orsolini, L.; Papanti, D.; Schifano, F. Novel psychoactive substances (NPS) and recent scenarios: Epidemiological, anthropological and clinical pharmacological issues. In Light in Forensic Science: Issues and Applications; Miolo, G., Stair, J.L., Zloh, M., Eds.; Royal Society of Chemistry: London, UK, 18 April 2018; Chapter 8, pp. 207–256. 2. Schifano, F.; Orsolini, L.; Duccio Papanti, G.; Corkery, J.M. Novel psychoactive substances of interest for psychiatry. World Psychiatry 2015, 14, 15–26. [CrossRef] [PubMed] 3. United Nations Office on Drugs and Crime (UNODC). World Drug Report 2018, Volume 3—Analysis of Drug Markets: Opiates, Cocaine, Cannabis, Synthetic Drugs; United Nations Office on Drugs and Crime: Vienna, Austria, 2018; Available online: https://www.unodc.org/wdr2018/ (accessed on 23 November 2018). 4. European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). EMCDDA–Europol 2017 Annual Report on the Implementation of Council Decision 2005/387/JHA; Publications Office of the European Union: Luxembourg, 2018; Available online: http://www.emcdda.europa.eu/system/files/publications/9282/ 20183924_TDAN18001ENN_PDF.pdf (accessed on 23 November 2018). 5. Orsolini, L.; Papanti, G.D.; Francesconi, G.; Schifano, F. Mind navigators of chemicals’ experimenters? A web-based description of e-psychonauts. Cyberpsychol. Behav. Soc. Netw. 2015, 18, 296–300. [CrossRef] [PubMed] 2 Brain Sci. 2018, 8, 221 6. Schifano, F.; Orsolini, L.; Papanti, D.; Corkery, J. NPS: Medical Consequences Associated with Their Intake. Curr. Top. Behav. Neurosci. 2017, 32, 351–380. [PubMed] 7. Sahai, M.A.; Davidson, C.; Dutta, N.; Opacka-Juffry, J. Mechanistic Insights into the Stimulant Properties of Novel Psychoactive Substances (NPS) and Their Discrimination by the Dopamine Transporter—In Silico and In Vitro Exploration of Dissociative Diarylethylamines. Brain Sci. 2018, 8, 63. [CrossRef] [PubMed] 8. Miolo, G.; Tucci, M.; Menilli, L.; Stocchero, G.; Vogliardi, S.; Scrivano, S.; Montisci, M.; Favretto, D. A Study on Photostability of Amphetamines and Ketamine in Hair Irradiated under Artificial Sunlight. Brain Sci. 2018, 8, 96. [CrossRef] [PubMed] 9. Parrott, A.C. Mood Fluctuation and Psychobiological Instability: The Same Core Functions Are Disrupted by Novel Psychoactive Substances and Established Recreational Drugs. Brain Sci. 2018, 8, 43. [CrossRef] [PubMed] 10. Cohen, K.; Weinstein, A. The Effects of Cannabinoids on Executive Functions: Evidence from Cannabis and Synthetic Cannabinoids—A Systematic Review. Brain Sci. 2018, 8, 40. [CrossRef] [PubMed] 11. Bonaccorso, S.; Metastasio, A.; Ricciardi, A.; Stewart, N.; Jamal, L.; Rujully, N.U.; Theleritis, C.; Ferracuti, S.; Ducci, G.; Schifano, F. Synthetic Cannabinoid use in a Case Series of Patients with Psychosis Presenting to Acute Psychiatric Settings: Clinical Presentation and Management Issues. Brain Sci. 2018, 8, 133. [CrossRef] [PubMed] 12. Frisoni, P.; Bacchio, E.; Bilel, S.; Talarico, A.; Gaudio, R.M.; Barbieri, M.; Neri, M.; Marti, M. Novel Synthetic Opioids: The Pathologist’s Point of View. Brain Sci. 2018, 8, 170. [CrossRef] [PubMed] 13. Martinotti, G.; Santacroce, R.; Pettorruso, M.; Montemitro, C.; Spano, M.C.; Lorusso, M.; di Giannantonio, M.; Lerner, A.G. Hallucinogen Persisting Perception Disorder: Etiology, Clinical Features, and Therapeutic Perspectives. Brain Sci. 2018, 8, 47. [CrossRef] [PubMed] 14. Schifano, F.; Chiappini, S.; Corkery, J.M.; Guirguis, A. Abuse of Prescription Drugs in the Context of Novel Psychoactive Substances (NPS): A Systematic Review. Brain Sci. 2018, 8, 73. [CrossRef] [PubMed] 15. Gittins, R.; Guirguis, A.; Schifano, F.; Maidment, I. Exploration of the Use of New Psychoactive Substances by Individuals in Treatment for Substance Misuse in the UK. Brain Sci. 2018, 8, 58. [CrossRef] [PubMed] 16. Wadsworth, E.; Drummond, C.; Deluca, P. The Dynamic Environment of Crypto Markets: The Lifespan of New Psychoactive Substances (NPS) and Vendors Selling NPS. Brain Sci. 2018, 8, 46. [CrossRef] [PubMed] 17. Miliano, C.; Margiani, G.; Fattore, L.; De Luca, M.A. Sales and Advertising Channels of New Psychoactive Substances (NPS): Internet, Social Networks, and Smartphone Apps. Brain Sci. 2018, 8, 123. [CrossRef] [PubMed] 18. Metastasio, A.; Negri, A.; Martinotti, G.; Corazza, O. Transitioning Bodies. The Case of Self-Prescribing Sexual Hormones in Gender Affirmation in Individuals Attending Psychiatric Services. Brain Sci. 2018, 8, 88. [CrossRef] 19. Catalani, V.; Prilutskaya, M.; Al-Imam, A.; Marrinan, S.; Elgharably, Y.; Zloh, M.; Martinotti, G.; Chilcott, R.; Corazza, O. Octodrine: New Questions and Challenges in Sport Supplements. Brain Sci. 2018, 8, 34. [CrossRef] [PubMed] © 2018 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)

Mesoporous nanocrystalline TiO2 loaded with ferulic acid for sunscreen and photo-protection: safety and efficacy assessment

In the present study, the use of surfactant-free mesoporous TiO2 combined with an antioxidant and photoprotecting agent, such as ferulic acid (FA), as a sunscreen was investigated for the first time. Ferulic acid is a natural antioxidant characterized by UV absorption capacity and radical scavenging activities and, due to these properties, it has been approved as an active ingredient in several skin lotions and sunscreens. However, despite the double function exerted by FA, the use of this molecule in the cosmetic field is limited by its poor stability. Aiming to overcome this drawback, mesoporous TiO2, prepared by using a sol-gel route assisted by a polyoxyethylene-polyoxypropylene block copolymer template followed by solvothermal treatment, was used as a matrix for the encapsulation of ferulic acid. The stability studies performed confirmed the ability of the prepared material to preserve the active molecule from degradation induced by light and, therefore, its properties. Antioxidant and anti-inflammatory activities of FA-loaded titania (TiO2@FA) and titania matrix (TiO2) were evaluated and high scavenging activity towards DPPH, ABTS and NO radicals were recorded. The in vitro assessment of the spectrophotometric Sun Protection Factor (SPF) was also performed and a value of 14.7 was observed for TiO2@FA while mesoporous TiO2 showed a lower SPF value equal to 2.6. These results suggested the potential application of the titania-doped FA as a "booster of SPF" that is able to enhance the SPF of a sunscreen. Furthermore, in vitro safety studies confirmed the biocompatibility of the prepared material and the absence of skin irritation