000121048 001__ 121048
000121048 005__ 20240319081020.0
000121048 0247_ $$2doi$$a10.1016/j.ijpharm.2022.122224
000121048 0248_ $$2sideral$$a131512
000121048 037__ $$aART-2022-131512
000121048 041__ $$aeng
000121048 100__ $$aSalido, S.
000121048 245__ $$aChitosan derivatives as nanocarriers for hLDHA inhibitors delivery to hepatic cells: A selective strategy for targeting primary hyperoxaluria diseases
000121048 260__ $$c2022
000121048 5060_ $$aAccess copy available to the general public$$fUnrestricted
000121048 5203_ $$aPrimary hyperoxalurias (PHs) are a group of inherited alterations of the hepatic glyoxylate metabolism that result in an excess of oxalate production by the oxidation of glyoxylate by the human lactate dehydrogenase A enzyme (hLDHA). The selective liver inhibition of this enzyme is one of the therapeutic strategies followed in the treatment of this disease. Even though several efforts have been recently performed using gene silencing by the RNA interference approach, small-molecule inhibitors that selectively reach hepatocytes are preferred since they present the advantages of a lower production cost and better pharmacological properties. In that sense, the design, synthesis, and physicochemical characterization by NMR, FTIR, DLS and TEM of two nanocarriers based on chitosan conjugates (1, non-redox-sensitive; 2, redox-sensitive) have been performed to (i) achieve the selective transport of hLDHA inhibitors into hepatocytes and (ii) their disruption once they reach the hepatocytes cytosol. Polymer 2 self-assembled into micelles in water and showed high drug loadings (19.8–24.5 %) and encapsulation efficiencies (31.9–40.8%) for the hLDHA inhibitors (I-III) tested. The non-redox-sensitive micelle 1 remained stable under different glutathione (GSH) concentrations (10 μM and 10 mM), and just a residual release of the inhibitor encapsulated was observed (less than 10 %). On the other hand, micelle 2 was sufficiently stable under in vitro physiological conditions (10 μM, GSH) but it quickly disassembled under the simulated reducing conditions present inside hepatocytes (10 mM GSH), achieving a 60 % release of the hLDHA inhibitor encapsulated after 24 h, confirming the responsiveness of the developed carrier to the high levels of intracellular GSH.
000121048 536__ $$9info:eu-repo/grantAgreement/ES/MCIU/RTI2018-098560-B-C22
000121048 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000121048 590__ $$a5.8$$b2022
000121048 592__ $$a0.906$$b2022
000121048 591__ $$aPHARMACOLOGY & PHARMACY$$b39 / 278 = 0.14$$c2022$$dQ1$$eT1
000121048 593__ $$aPharmaceutical Science$$c2022$$dQ1
000121048 594__ $$a10.5$$b2022
000121048 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000121048 700__ $$aAlejo-Armijo, A.
000121048 700__ $$aParola, A.J.
000121048 700__ $$0(orcid)0000-0002-6873-5244$$aSebastián, V.$$uUniversidad de Zaragoza
000121048 700__ $$0(orcid)0000-0002-9324-0446$$aAlejo, T.$$uUniversidad de Zaragoza
000121048 700__ $$0(orcid)0000-0002-2966-9088$$aIrusta, S.$$uUniversidad de Zaragoza
000121048 700__ $$0(orcid)0000-0003-3165-0156$$aArruebo, M.$$uUniversidad de Zaragoza
000121048 700__ $$aAltarejos, J.
000121048 7102_ $$15005$$2555$$aUniversidad de Zaragoza$$bDpto. Ing.Quím.Tecnol.Med.Amb.$$cÁrea Ingeniería Química
000121048 7102_ $$15005$$2790$$aUniversidad de Zaragoza$$bDpto. Ing.Quím.Tecnol.Med.Amb.$$cÁrea Tecnologi. Medio Ambiente
000121048 773__ $$g627 (2022), 122224 [12 pp.]$$pInt. j. pharm.$$tInternational Journal of Pharmaceutics$$x0378-5173
000121048 8564_ $$s5555350$$uhttps://zaguan.unizar.es/record/121048/files/texto_completo.pdf$$yVersión publicada
000121048 8564_ $$s2358417$$uhttps://zaguan.unizar.es/record/121048/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000121048 909CO $$ooai:zaguan.unizar.es:121048$$particulos$$pdriver
000121048 951__ $$a2024-03-18-16:03:22
000121048 980__ $$aARTICLE