title: Self assembled hyaluronic acid nanoparticles as a potential carrier for targeting the inflamed intestinal mucosa.
abstract: To develop a nanoparticulate drug carrier for targeting of the inflamed intestinal mucosa, amphiphilic hyaluronic acid (HA) conjugates were synthesized, which could form self-assembled nanoparticles (NPs) in aqueous solution and budesonide (BDS) was loaded into the HANPs. Their particle sizes were in the range of 177 to 293nm with negative surface charge. The model of inflammatory CACO-2 cells was utilized to investigate the therapeutic potential of budesonide loaded HA nanocarriers. The highest expression of CD44 receptors was found on inflamed Caco-2 cells, as determined by flow cytometry. FITC-labeled HANPs revealed greater uptake in inflamed CACO-2 cells compared to untreated CACO-2 and CD44-negative cell lines, NIH3T3. BDS loaded HANPs displayed almost no toxicity indicating HANPs are excellent biocompatible nano-carriers. BDS loaded HANPs demonstrated higher anti-inflammatory effect on IL-8 and TNF-α secretion in inflamed cell model compared to the same dose of free drug. These results revealed the promising potential of HA nanoparticles as a targeted drug delivery system for IBD treatment.
authors.affiliation: Nanomedicine and Biomaterial Lab., Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, 16 Azar St, Enqelab Sq, Tehran 1417614411, Iran.
authors.forename: Seyed Yaser
authors.initials: SY
authors.lastname: Vafaei
authors.affiliation: Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, 16 AzarSt, Enqelab Sq, Tehran 1417614411, Iran.
authors.forename: Motahareh
authors.initials: M
authors.lastname: Esmaeili
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, 16 Azar St, Enqelab Sq, Tehran 1417614411, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
authors.affiliation: Nanomedicine and Biomaterial Lab., Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, 16 Azar St, Enqelab Sq, Tehran 1417614411, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, 16 AzarSt, Enqelab Sq, Tehran 1417614411, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Atyabi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, 16 AzarSt, Enqelab Sq, Tehran 1417614411, Iran.
authors.forename: Seyed Naser
authors.initials: SN
authors.lastname: Ostad
authors.affiliation: Nanomedicine and Biomaterial Lab., Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, 16 Azar St, Enqelab Sq, Tehran 1417614411, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, 16 AzarSt, Enqelab Sq, Tehran 1417614411, Iran. Electronic address: dinarvand@tums.ac.ir.
authors.forename: Rassoul
authors.initials: R
authors.lastname: Dinarvand
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001692:Biological Transport; D019819:Budesonide / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D018938:Caco-2 Cells; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D065546:Drug Liberation; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D057927:Hydrophobic and Hydrophilic Interactions; D007249:Inflammation / Q000188:drug therapy; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D018960:Hyaluronan Receptors; D019819:Budesonide; D006820:Hyaluronic Acid
keywords: Budesonide; Hyaluronic acid; Inflammatory bowel disease; Self-assembling nanosystems; Targeted drug delivery