title: Wheat germ agglutinin anchored chitosan microspheres of reduced brominated derivative of noscapine ameliorated acute inflammation in experimental colitis.
abstract: Reduced brominated derivative of noscapine (Red-Br-Nos, EM012), has potent anti-inflammatory property. However, physicochemical limitations of Red-Br-Nos like low aqueous solubility (0.43×10(-3) g/mL), high lipophilicity (logP∼2.94) and ionization at acidic pH greatly encumber the scale-up of oral drug delivery systems for the management of colitis. Therefore, in present investigation, chitosan microspheres bearing Red-Br-Nos (CTS-MS-Red-Br-Nos) were prepared by emulsion polymerization method and later coated with wheat germ agglutinin (WGA-CTS-MS-Red-Br-Nos) to boost the bioadhesive property. The mean particle size and zeta-potential of CTS-MS-Red-Br-Nos were measured to be 10.5±5.4 μm and 8.1±2.2 mV, significantly (P<0.05) lesser than, 30.2±3.2 μm and 19.2±2.3 mV of WGA-CTS-MS-Red-Br-Nos. Furthermore, various spectral techniques like SEM, FT-IR, DSC and PXRD substantiated that Red-Br-Nos was molecularly dispersed in tailored microspheres in amorphous state. Surface bioadhesive property of WGA-CTS-MS-Red-Br-Nos promoted the affinity toward colon mucin cells in simulated colonic fluid (SCF, pH∼7.2). In vitro release studies carried out on WGA-CTS-MS-Red-Br-Nos and CTS-MS-Red-Br-Nos indicated that SCF with colitis milieu (pH∼4.7) favored the controlled release of Red-Br-Nos, owing to solubilization at acidic pH. Consistently, in vivo investigation also demonstrated the utility of WGA-CTS-MS-Red-Br-Nos, which remarkably attenuated the DSS encouraged neutrophil infiltration, myeloperoxidase activity, and pro-inflammatory cytokine production in C57BL6J mice, as compared to CTS-MS-Red-Br-Nos and Red-Br-Nos suspension. The noteworthy anti-inflammatory activity of WGA-CTS-MS-Red-Br-Nos against acute colitis may be attributed to enhanced drug delivery, affinity and utmost drug exposure at inflamed mucosal layers of colon. In conclusion, WGA-CTS-MS-Red-Br-Nos warrants further in-depth in vitro and in vivo investigations to scale-up the technology for clinical translation.
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Panjab, India.
authors.forename: Kamalpreet
authors.initials: K
authors.lastname: Kaur
authors.affiliation: Department of Pharmacology, Chandigarh College of Pharmacy, Mohali, Panjab, India.
authors.forename: Rupinder Kaur
authors.initials: RK
authors.lastname: Sodhi
authors.affiliation: Dr. B.R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi, India.
authors.forename: Anju
authors.initials: A
authors.lastname: Katyal
authors.affiliation: Department of Biology, Georgia State University, Atlanta, GA, USA.
authors.forename: Ritu
authors.initials: R
authors.lastname: Aneja
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Panjab, India.
authors.forename: Upendra Kumar
authors.initials: UK
authors.lastname: Jain
authors.affiliation: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
authors.forename: Om Prakash
authors.initials: OP
authors.lastname: Katare
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Panjab, India. Electronic address: jitenderpharmacy@gmail.com.
authors.forename: Jitender
authors.initials: J
authors.lastname: Madan
mesh_terms: D000818:Animals; D001966:Bromine / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D048271:Chitosan / Q000737:chemistry*; D003092:Colitis / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D009665:Noscapine / Q000737:chemistry / Q000627:therapeutic use*; D033362:Powder Diffraction; D014909:Wheat Germ Agglutinins / Q000737:chemistry*
chemical_list: D014909:Wheat Germ Agglutinins; D009665:Noscapine; D048271:Chitosan; D001966:Bromine
keywords: Chitosan; Colitis; Inflammation; Red-Br-Nos; Wheat germ agglutinin