Tricyclic antidepressants, as doxepin hydrochloride (DH), may have analgesic local effect due to its biochemical mechanism of action. Delivery of DH directly to the oral cavity could be an interesting alternative for toothache due to its analgesic local effect. One problem associated with the mucosal administration routes is the short residence time of the dosage form on the mucosal membranes. In this sense, we have developed new doxepin mucoadhesive films able of reducing pain and increasing the effectiveness of treatment. For this purpose, we tested three different polymers: chitosan, sodium hydroxypropylmethylcellulose (HPMC) and sodium carboxymethylcellulose (SCMC) in film elaboration. The results obtained show that all films are hydrophilic matrices that absorb water when placed in an aqueous media. All the films hydrated very quickly, reaching high percentage of swelling after just few minutes (5 min for SCMC, 2 min for HPMC and 30 min for chitosan). Moreover, the SCMC and HPMC films were dissolved whereas chitosan was not dissolved. Dissolution also leads to viscous liquids with a higher retention time over mucosal surfaces what may lead to adhesive interactions. In vitro permeation studies showed that for all the formulations studied, SCMC (19.91%), HPMC (69.5%) and chitosan (24.17%), the percentage of drug permeated increased compared to the drug solution (8.26%). Specifically the HPMC film presents greater amounts of doxepin permeated (49.27 ± 4.47 mg/cm 2 ).
Therapies against stroke can restore the blood supply but cannot prevent the ischemic damage nor stimulate the recovery of the infarcted zone. The neuroglobin protein plays an important role in the neuro-regeneration process after stroke; however, the method for its effective systemic application has not been identified yet, as neuroglobin is unable to pass through the blood-brain barrier. Previously, we developed different types of sodium hyaluronate nanoparticles, which successfully cross the blood-brain barrier after stroke. In this work, these nanoparticles have been used to carry neuroglobin through the bloodstream to the nerve cells in rats submitted to stroke. We have biosynthesized rat-recombinant neuroglobin and determined the formulation of sodium hyaluronate nanoparticles loaded with neuroglobin, as well as its size and ζ-potential, encapsulation efficiently, in vitro release, and its kinetic of liberation. The results show that the formulation achieved is highly compatible with pharmaceutical use and may act as a delivery system to transport neuroglobin within the blood. We have found that this formulation injected intravenously immediately after stroke reached the damaged cerebral parenchyma at early stages (2 h). Neuroglobin colocalizes with its nanocarriers inside the nerve cells and remains after 24 h of reperfusion. In conclusion, the systemic administration of neuroglobin linked to nanoparticles is a potential neuroprotective drug-delivery strategy after stroke episodes.
This work analyses the role of proteoglycans on skin ageing, influenced by the presence of glycosylated proteins, which exercise diverse functions on the skin. They are essential components that restore the cells, providing hydration, maintaining hydration of the extracellular matrix, preventing the formation of wrinkles thanks to their ability to combine to other molecules such as collagen or hyaluronic acid and favouring the smoothness of the skin texture. The use of these proteins is a very recent and promising topic, since their application may revolutionize skin ageing therapies. Of the existing proteoglycans, decorin, versican and perlecan are of special note, playing a fundamental role on skin. R esum e Nous avons analys e dans cette etude le rôle des prot eoglycanes dans le vieillissement de la peau, conditionn e par la pr esence des prot eines glycosyl ees qui exercent plusieurs fonctions sur la peau. Ce sont des composants essentiels qui restaurent les cellules, fournissent de l'hydratation en maintenant l'hydratation de la matrice extracellulaire en evitant la formation de rides cutan ees grâce a sa capacit e de se combiner a d'autres mol ecules tels que le collag ene ou l'acide hyaluronique qui favorisent la douceur de la peau. L'utilisation de ces prot eines est un des sujets les plus r ecents et prometteurs, etant donn e que son application peut repr esenter une r evolution quant aux th erapies qui luttent contre le vieillissement cutan e. Parmi les prot eoglycanes ressortent la d ecorine, le versicane et le perl ecane qui jouent un rôle fondamental sur le derme.
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