Format

Send to

Choose Destination
Colloids Surf B Biointerfaces. 2015 Aug 1;132:225-35. doi: 10.1016/j.colsurfb.2015.05.022. Epub 2015 May 21.

Wheat germ agglutinin anchored chitosan microspheres of reduced brominated derivative of noscapine ameliorated acute inflammation in experimental colitis.

Author information

1
Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Panjab, India.
2
Department of Pharmacology, Chandigarh College of Pharmacy, Mohali, Panjab, India.
3
Dr. B.R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi, India.
4
Department of Biology, Georgia State University, Atlanta, GA, USA.
5
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
6
Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Panjab, India. Electronic address: jitenderpharmacy@gmail.com.

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.

KEYWORDS:

Chitosan; Colitis; Inflammation; Red-Br-Nos; Wheat germ agglutinin

PMID:
26047885
DOI:
10.1016/j.colsurfb.2015.05.022
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center