Optimization of pH-Responsive Polymeric Nanoparticles for Colon-Targeted Delivery of 5-Fluorouracil Using Quality by Design

Original Research | 2026 | Volume 1 | Issue 2 | Page 113-123

1. Tushar Chauhan, Department of Pharmacy, HRIT University, Ghaziabad

2. Dr. Meenu Singh, Assistant Professor, Department of Pharmacy, HRIT University, Duhai Ghaziabad

Optimization of pH-Responsive Polymeric Nanoparticles for Colon-Targeted Delivery of 5-Flu.

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Corresponding Author: - 

Tushar Chauhan, 

Department of Pharmacy, 

HRIT University, Ghaziabad 

Abstract

Background: The conventional oral administration of 5-Fluorouracil (5-FU) suffers from early drug release, poor colon specificity, low bioavailability, and systemic toxicity, which have resulted in reduced efficacy of the drug in colorectal disorders. pH-sensitive polymeric nanoparticles have been identified as a promising tool for site-specific and controlled drug delivery.

Aim: The present study aimed to develop and optimize pH-responsive polymeric nanoparticles of 5-Fluorouracil using chitosan, PLGA, and Eudragit S100 for targeted colon drug delivery and to evaluate their physicochemical characteristics, release behavior, stability, and in vitro–in vivo correlation.

Methods: The polymeric nanoparticles were developed using solvent evaporation technique and optimized using Quality by Design concept using Box-Behnken Design. The optimized formulation was evaluated for particle size, polydispersity index, zeta potential, entrapment efficiency, morphology, in vitro drug release, release kinetics, stability, and IVIVC.

Results: The optimization of the nanoparticles resulted in a nanoparticle size of 188.5 ± 4.2 nm, PDI of 0.214 ± 0.018, zeta potential of −28.7 ± 1.4 mV, and EE of 88.2 ± 2.1%. There was drug release that was dependent on pH, with drug release of 92.8% achieved at pH 7.4. In terms of kinetics of release, it follows Korsmeyer-Peppas model with R² value of 0.992. Stability study indicated six-month stability, whereas excellent IVIVC (R² = 0.999).

Conclusion: The designed pH-sensitive polymeric nanoparticles were found to exhibit promising physicochemical properties, colon-specific drug release, excellent stability, and high predictability, thus, indicating their potential as an effective.

Keywords: 5-Fluorouracil; Colon-targeted drug delivery; pH-responsive polymeric nanoparticles; Quality by Design; In vitro–in vivo correlation.