title: Enzyme/pH dual sensitive polymeric nanoparticles for targeted drug delivery to the inflamed colon.
abstract: Novel nanoparticles whose drug release profiles are controlled by both enzyme and pH were prepared for the colon-specific drug delivery using a polymeric mixture of enzyme-sensitive azo-polyurethane and pH-sensitive Eudragit S100 (ES-Azo.pu). The enzyme/pH dual sensitive nanoparticles were designed to release a drug based on a two-fold approach which specifically aimed to target drug delivery to the inflamed colon while preventing the burst release of drugs in the stomach and small intestine. Single pH-sensitive (ES) and dual sensitive (ES-Azo.pu) nanoparticles were prepared using an oil-in-water emulsion solvent evaporation method and coumarin-6 (C-6) was used as a model drug. The successful formation of ES and ES-azo.pu nanoparticles that have 214 nm and 244 nm in mean particle size, respectively, was confirmed by scanning electron microscopy and qNano. ES nanoparticles showed almost 100% of burst drug release at pH 7.4, whereas ES-Azo.pu nanoparticles prevented the burst drug release at pH 7.4, followed by a sustained release phase thereafter. Furthermore, ES-Azo.pu nanoparticles exhibited enzyme-triggered drug release in the presence of rat cecal contents obtained from a rat model of colitis. An in vivo localization study in rat gastrointestinal tract demonstrated that ES-Azo.pu nanoparticles were selectively distributed in the inflamed colon, showing 5.5-fold higher C-6 than ES nanoparticles. In conclusion, the enzyme/pH dual sensitive nanoparticles presented in this study can serve as a promising strategy for colon-specific drug delivery against inflammatory bowel disease and other colon disorders.
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, South Korea.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Naeem
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, South Korea.
authors.forename: Wooseong
authors.initials: W
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, South Korea.
authors.forename: Jiafu
authors.initials: J
authors.lastname: Cao
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, South Korea.
authors.forename: Yunjin
authors.initials: Y
authors.lastname: Jung
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, South Korea. Electronic address: jinwook@pusan.ac.kr.
authors.forename: Jin-Wook
authors.initials: JW
authors.lastname: Yoo
mesh_terms: D000818:Animals; D003092:Colitis / Q000188:drug therapy; D003106:Colon / Q000378:metabolism* / Q000473:pathology*; D003374:Coumarins / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D015212:Inflammatory Bowel Diseases; D008297:Male; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011140:Polyurethanes; D051381:Rats; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D003374:Coumarins; D004337:Drug Carriers; D011108:Polymers; D011140:Polyurethanes; D013438:Sulfhydryl Compounds; C508172:coumarin-6-sulfonyl chloride
keywords: Azo-polyurethane; Colon-specific delivery; Dual-sensitive nanoparticles; Eudragit S100; Inflammatory bowel disease