El Leithy E.S.Abdel-Bar H.M.Ali R.A.-M.Department of Pharmaceutics and Industrial PharmacyFaculty of PharmacyOctober University for Modern Sciences and Arts (MSA)CairoEgypt; Department of Pharmaceutics and Industrial PharmacyFaculty of PharmacyHelwan UniversityCairoEgypt; Department of PharmaceuticsFaculty of PharmacyUniversity of Sadat CityMenoufiaEgypt2020-01-092020-01-0920193785173https://doi.org/10.1016/j.ijpharm.2019.118708PubMed ID 31593805https://t.ly/YZR0YScopusMSA Google ScholarThe aim of this study was to prove a prolonged control of glucose levels, in rats, by the oral use of insulin folate-chitosan nanoparticles (FA-CS NPs). It was possible to prepare positively charged NPs with an average particle size of 288 � 5.11 nm and >80% entrapment efficiency. The system was able to enhance the stability of insulin in presence of GIT enzymes, with less than 10% release at pH 1.2 and an 8 hr released amount of 38.92 � 4.52% in PBS pH 7.4. A 5 fold enhancement in insulin intestinal permeability and cellular uptake over insulin solution was proven. The cellular uptake pathways was found to occur by several mechanisms. Besides, cell compatibility and absence of histopathological alterations was also demonstrated. Finally, a controlled blood glucose level for 8 h in rats. These results anticipated FA-CS NPs as a promising oral insulin candidate. � 2019 Elsevier B.V.EnglishCellular uptakeChitosanControlled blood glucoseFolic acidInsulinOral deliveryantidiabetic agentchitosan nanoparticlefolate chitosan nanoparticlefolic acidglucoseinsulinunclassified druganimal experimentanimal modelantidiabetic activityArticleCaco-2 cell linecell viabilitycontrolled studycytotoxicityenzymatic degradationglucose blood levelhistopathologyhumanhuman cellin vivo studyinsulin blood levelinsulin releaseinternalizationintestine mucosa permeabilitymalemean residence timenonhumanparticle sizepHpriority journalratzeta potentialArticlehttps://doi.org/10.1016/j.ijpharm.2019.118708PubMed ID 31593805