Azacarbazole n-3 and n-6 polyunsaturated fatty acids ethyl esters nanoemulsion with enhanced efficacy against Plasmodium falciparum

作     者：Anna Jaromin Silvia Parapini Nicoletta Basilico Magdalena Zaremba-Czogalla Agnieszka Lewi´nska Agnieszka Zag´orska Maria Walczak Bozena Tyliszczak Aleksandra Grzeszczak MarcinŁukaszewicz Łukasz Kaczmarek Jerzy Gubernator 

作者机构：Department of Lipids and LiposomesFaculty of BiotechnologyUniversity of WroclawWroclawPoland Dipartimento di Scienze Biomediche per la SaluteUniversit`a degli Studi di MilanoMilanItaly Dipartimento di Scienze BiomedicheChirurgiche e OdontoiatricheUniversit`a degli Studi di MilanoMilanItaly Faculty of ChemistryUniversity of WroclawWroclawPoland Department of Medicinal ChemistryJagiellonian University Medical CollegeCracowPoland Chair and Department of ToxicologyJagiellonian University Medical CollegeFaculty of PharmacyCracowPoland Instytute of Materials ScienceCracow University of TechnologyCracowPoland Department of BiotransformationFaculty of BiotechnologyUniversity of WroclawWroclawPoland Pharmaceutical Research InstituteWarsawPoland 

出 版 物：《Bioactive Materials》 (生物活性材料（英文）)

年 卷 期：2021年第6卷第4期

页      面：1163-1174页

核心收录：

学科分类：0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 1002[医学-临床医学] 08[工学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 0805[工学-材料科学与工程（可授工学、理学学位）] 0836[工学-生物工程] 10[医学] 

基　　金：the statutory activity of subsidy from the Polish Ministry of Science and Higher Education for the Faculty of Biotechnology and Faculty of Chemistry of the University of Wroclaw and by Ministero dell’Istruzione dell’Universit`a e della Ricerca[PRIN 2015.4JRJPP_004].Publication costs were supported by Wroclaw Center of Biotechnology program“The Leading National Research Center(KNOW)for years 2014-2018” 

主　　题：Azacarbazoles Flax oil n-3 and n-6 polyunsaturated fatty acids ethyl esters Nanoemulsion P.falciparum Malaria 

摘      要：Alternative therapies are necessary for the treatment of malaria due to emerging drug ***,many promising antimalarial compounds have poor water solubility and suffer from the lack of suitable delivery systems,which seriously limits their *** address this problem,we synthesized a series of azacarbazoles that were evaluated for antimalarial activity against D10(chloroquine-sensitive)and W2(chloroquine-resistant)strains of *** most active compound,9H-3-azacarbazole(3),was encapsulated in a novel o/w nanoemulsion consisting of ethyl esters of polyunsaturated fatty acids n-3 and n-6 obtained from flax oil as the oil phase,Smix(Tween 80 and Transcutol HP)and *** formulation was further analyzed using transmission electron microscopy,dynamic light scattering and in vitro and in vivo *** was shown that droplets of the 3-loaded nanosystem were spherical,with satisfactory stability,without cytotoxicity towards fibroblasts and intestinal cell lines at concentrations corresponding to twice the IC50 for ***,the nanoemulsion with this type of oil phase was internalized by Caco-2 ***,pharmacokinetics demonstrated rapid absorption of compound 3(tmax=5.0 min)after intragastric administration of 3-encapsulated nanoemulsion at a dose of 0.02 mg/kg in mice,with penetration of compound 3 to deep *** 3-encapsulated nanoemulsion was found to be 2.8 and 4.2 times more effective in inhibiting the D10 and W2 strains of the parasite,respectively,compared to non-encapsulated *** findings support a role for novel o/w nanoemulsions as delivery vehicles for antimalarial drugs.