Affiliation:
1. Department of Pharmaceutical Chemistry, Bharati Vidyapeeth University, Poona College of
Pharmacy, Pune, Maharashtra 411038, India
2. Department of Pharmaceutical Chemistry, Amity Institute of Pharmacy, Lucknow, Amity University Uttar Pradesh,
Noida 226028, India
Abstract
Background::
Adverse effects induced by upper GIT release of mycophenolic acid (MPA) and
its prodrug mycophenolate mofetil (MMF) have created a great deal of concern in the treatment of inflammatory
bowel disease (IBD).
Objective::
The goal of this work was to create a polymer-based prodrug (MDS) by attaching MPA to
dextran to enable colon-targeted drug delivery and, as a result, minimize the adverse effects of MPA and
MMF.
Methods::
MPA was conjugated with dextran via a bio-cleavable ester bond utilizing the EDCI coupling
process. MDS was characterized by spectral analysis. The degree of substitution was estimated by complete
hydrolysis of the conjugate in phosphate buffer (pH= 9.0). The prodrug was screened for gastrosparing
potential using TNBS-induced colitis model in Wistar rats.
Results::
Physicochemical parameters, such as degree of substitution (9.32 mg MPA/100mg of MDS),
DSC study (Melting point: 194.3°C), and molecular weight (70307 Da) were determined. The significant
mitigating effect of MDS on quantifying parameters of TNBS-induced colitis, i.e., disease activity score
rate (0.72±0.35), colon to body weight ratio (0.024±0.003), MPO activity (36.9±0.67mU/100mg of tissue),
ulcerogenic potential (2.85±0.08), and histopathological data showed that prodrug restored distorted
colonic architecture to normal.
Conclusion::
Hydrophilicity was improved, allowing for more effective transport of MPA to the colon. In
TNBS-induced colitis, the prodrug was found 1.5 times more efficient than MPA at lowering quantifiable
markers of colonic inflammation. Histopathology data showed that MDS might be developed as a potential
approach for directing MPA to the colon for the treatment of IBD.
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmaceutical Science,Molecular Medicine