title: Colon-targeted delivery of budesonide using dual pH- and time-dependent polymeric nanoparticles for colitis therapy.
abstract: Single pH-dependent drug delivery systems have been widely used for colon-targeted delivery, but their efficiency is often hampered by the variation in gut pH. To overcome the limitation of single pH-dependent delivery systems, in this study, we developed and evaluated the therapeutic potential of budesonide-loaded dual pH/time-dependent nanoparticles (NPs) for the treatment of colitis. Eudragit FS30D was used as a pH-dependent polymer, and Eudragit RS100 as a time-dependent controlled release polymer. Single pH-dependent NPs (pH_NPs), single time-dependent NPs (Time_NPs), and dual pH/time-dependent NPs (pH/Time_NPs) were prepared using the oil-in-water emulsion method. The physicochemical properties and drug release profiles of these NPs in gastrointestinal (GI) tract conditions were investigated. The therapeutic potential and in vivo distribution of the NPs were evaluated in a dextran sulfate sodium (DSS)-induced colitis mice model. The pH/Time_NPs prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. The in vivo distribution study in the mice GI tract demonstrated that pH/Time_NPs were more efficiently delivered to the inflamed colon than pH_NPs were. Compared to the single pH_NPs-treated group, the pH/Time_NPs-treated group showed increased body weight and colon length and markedly decreased disease activity index, colon weight/length ratios, histological damage, and inflammatory cell infiltration in colon tissue. Our results demonstrate that the dual pH/time-dependent NPs are an effective oral colon-targeted delivery system for colitis therapy.
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Naeem
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Moonjeong
authors.initials: M
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Jiafu
authors.initials: J
authors.lastname: Cao
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Yujeong
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Pusan National University School of Medicine, Yangsan, South Korea.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ikram
authors.affiliation: Pusan National University School of Medicine, Yangsan, South Korea.
authors.forename: Sik
authors.initials: S
authors.lastname: Yoon
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Jaewon
authors.initials: J
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Hyung Ryong
authors.initials: HR
authors.lastname: Moon
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Min-Soo
authors.initials: MS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Yunjin
authors.initials: Y
authors.lastname: Jung
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Jin-Wook
authors.initials: JW
authors.lastname: Yoo
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D019819:Budesonide / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D003092:Colitis / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003692:Delayed-Action Preparations; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles; D011109:Polymethacrylic Acids / Q000737:chemistry; D013997:Time Factors
chemical_list: D000180:Acrylic Resins; D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; C050528:Eudragit RS; D019819:Budesonide; D016264:Dextran Sulfate
keywords: budesonide; colon-specific delivery; dual-sensitive delivery; inflammatory bowel disease