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    Bio-based topical system for enhanced salicylic acid delivery: preparation and performance of gels
    (Wiley, 2016) Langasco, Rita; Spada, Gianpiera; Tanriverdi, Sakine Tuncay; Rassu, Giovanna; Giunchedi, Paolo; Ozer, Ozgen; Gavini, Elisabetta
    ObjectivesNew salicylic acid (SA)-loaded gels were developed using excipients made from renewable materials, and our goal was to improve drug permeation in the topical treatment of acne vulgaris. MethodsWe studied the preparation parameters to obtain suitable gel formulations. Only naturally occurring polymers were used as gelling agents. Two hydrogels and three lipogels were selected and characterized in terms of drug loading, pH, viability cells, rheology, mechanical properties and in vitro permeation; these hydrogels and lipogels were compared with the traditional ointment. We also evaluated skin parameters before and after gel application. Key findingsThe formulations that we studied are non-Newtonian fluids; they have high drug loading and suitable mechanical properties. Lipogels exhibit a slower and more linear in vitro permeation profile compared with hydrogels. The different vehicles that we used affected drug permeation and improve patient compliance. Cytotoxicity studies suggest that all of the formulations are non-toxic. ConclusionsLipogels demonstrate appropriate technological features and improved performance compared with the traditional ointment with regard to their composition. Lipogels may represent a new bio-based topical system for SA delivery. The use of green' excipients leads to skin-friendly' formulations that are able to satisfy environmental safety.
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    Neuroprotective Effects of Engineered Polymeric Nasal Microspheres Containing Hydroxypropyl-beta-cyclodextrin on beta-Amyloid (1-42)-Induced Toxicity
    (Elsevier Science Inc, 2016) Yalcin, Ayfer; Soddu, Elena; Bayrakdar, Ezgi Turunc; Uyanikgil, Yigit; Kanit, Lutfiye; Armagan, Guliz; Rassu, Giovanna; Gavini, Elisabetta; Giunchedi, Paolo
    beta-Amyloid (A beta) plaques are the key neurotoxic assemblies in Alzheimer disease. It has been suggested that an interaction occurs between membrane cholesterol and A beta aggregation in the brain. Cyclodextrins can remove cholesterol from cell membranes and change receptor function. This study aimed to investigate the effect of hydroxypropyl-beta-cyclodextrin (HP-CD) polymeric microspheres, based on chitosan or sodium alginate, on the levels of lipid peroxidation, reactive oxygen species production, and mitochondrial function in brain synaptosomes. The effect of microspheres on DNA fragmentation, the expression of Bcl-2, Bax, and Apex1 mRNAs in rat hippocampus after A beta(1-42) peptide-induced neurotoxicity was also evaluated. Comparison with HP-CD raw material was performed. A beta(1-42) treatment significantly decreased the mitochondrial activity of Apex1 and Bcl-2 mRNAs, induced DNA fragmentation, and increased mRNA levels of Bax. Treatment with HP-CD microspheres against A beta(1-42) significantly reduced DNA fragmentation and increased the Bcl-2/Bax mRNA ratio and mitochondrial function. In addition, HP-CD microspheres used against A beta(1-42) decreased the levels of lipid peroxidation and reactive oxygen species production. These results indicate that nasally administered spraydried HP-CD microspheres are able to provide protection against A beta(1-42)-induced neurotoxicity, due to the suppressed levels of oxidative stress and apoptotic signals in the rat hippocampus. (C) 2016 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
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    Potential neuroprotective effects of 2-hydroxypropyl-? cyclodextrin against amyloid ? (1-42)-induced neurotoxicity on the rat hippocampus
    (Taylor & Francis Ltd, 2024) Yalcin, Ayfer; Turunc, Ezgi; Kaplan, Mehmet Mahsum; Uyanikgil, Yigit; Erzurumlu, Yalcin; Gavini, Elisabetta; Kanit, Lutfiye
    The neurodegenerative mechanisms of Alzheimer's disease (AD) are not fully understood, but it is believed that amyloid beta (A beta) peptide causes oxidative stress, neuroinflammation, and disrupts metabotropic glutamate receptor 5 (mGluR5) signaling by interacting with cholesterol and caveolin-1 (Cav-1) in pathogenic lipid rafts. This study examined the effect of 2-hydroxypropyl-beta-cyclodextrin (HP-CD) on cholesterol, oxidative stress (total oxidant status), neuroinflammation (TNF-alpha), and mGluR5 signaling molecules such as PKC beta 1, PKC beta 2, ERK1/2, CREB, BDNF, and NGF in A beta (1-42)-induced neurotoxicity. The Sprague-Dawley rats were divided into four groups: control (saline), A beta (1-42), HP-CD (100 mg/kg), and A beta (1-42) + HP-CD (100 mg/kg). All groups received bilateral stereotaxic injections of A beta (1-42) or saline into the hippocampus. After surgery, HP-CD was administered intraperitoneally (ip) for 7 days. Cholesterol, TNF-alpha, and TOS levels were measured in synaptosomes isolated from hippocampus tissue using spectrophotometry, fluorometry, and enzyme immunoassay, respectively. The gene expressions of Cav-1, mGluR5, PKC beta 1, PKC beta 2, ERK1/2, CREB, BDNF, and NGF in hippocampus tissue were evaluated using reverse transcription PCR after real-time PCR analysis. Treatment with A beta (1-42) significantly elevated cholesterol, TOS, TNF-alpha, Cav-1, PKC beta 2, and ERK1/2 levels. Additionally, mGluR5, CREB, and BDNF levels were shown to be lowered. HP-CD reduced cholesterol, TOS, and TNF-alpha levels while increasing mGluR5, CREB, and BDNF in response to A beta (1-42) treatment. These findings indicate that HP-CD may have neuroprotective activity due to the decreased levels of cholesterol, oxidative stress, and neuroinflammation, as well as upregulated levels of mGluR5, CREB, and BDNF.
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    Prolonged skin retention of clobetasol propionate by bio-based microemulsions: a potential tool for scalp psoriasis treatment
    (Taylor & Francis Ltd, 2018) Langasco, Rita; Tanriverdi, Sakine Tuncay; Ozer, Ozgen; Roldo, Marta; Cossu, Massimo; Rassu, Giovanna; Giunchedi, Paolo; Gavini, Elisabetta
    Novel effective and cosmetically acceptable formulations are needed for the treatment of scalp psoriasis, due to the poor efficacy of the current products. The challenge in developing safe, efficient, and convenient delivery systems for this drug was addressed in the present work by formulating clobetasol propionate-loaded W/O microemulsions (MEs). Pseudo-ternary phase diagrams were constructed by using a combination of biocompatible and biodegradable excipients. Characterization studies demonstrated that selected MEs had suitable technological features such as being Newtonian fluids, possessing low viscosity, and high thermodynamic stability. Photomicrographs showed a significant alteration of the skin structure after treatment with MEs, and a preferential concentration of these in the stratum corneum and epidermis. These data, together with ex vivo permeation results, suggested an enhanced topical targeted effect due to an increased drug retention efficacy in the upper skin layers, as desired. Moreover, the bio-based excipients selected could contribute to the healing of the psoriatic scalp. In this way, the improvement of clobetasol efficacy is combined with the useful properties of the microemulsion components and with environmental safety.