Design, Development And Optimisation Of Capecitabine Loaded Eudragit, Pectin, And Sodium Hyaluronatenanoparticles For Oral Cytotoxic Colon Specific Drug Delivery

Abstract

Background: Polymeric nanoparticles have indeed garnered significant attention in the realm of controlled-release drug delivery systems. The versatility and advantageous properties of polymeric nanoparticles make them a promising vehicle for controlled drug delivery.

Objective: Design, development, and optimisation of capecitabine-loaded polymeric nanoparticles for targeted drug delivery.

Methods: Formulations of core nanoparticles were coated with FS100 Eudragit with a ratio of 1:4 by the emulsion solvent evaporation method. Capecitabine-loaded nanoparticles were successfully prepared by optimising various variables using the principles of the design of experiments. Numerical and graphical optimisation was observed using Design Expert software to optimise the final batch of nanoparticles. The optimisation focused on the effect of four independent factors on particle size, % encapsulation efficiency, and drug release in HCl and PBS. The nanoparticles devised in this study were intended to passively target colon cancer by utilising enhanced absorption, improving antigen presentation, and providing longer circulation times.

Results: The results of the FTIR spectra indicated that the drugs are compatible with each other, with no drug interactions observed. An analytical method was developed and validated for the drug formulation, employing techniques such as SEM, DSC, PDI, zeta potential in particle distribution, PXRD, release kinetics, and in vitro cell cytotoxicity studies. All variables were found to be within specified limits, and the models of responses were found to be significant. The experimental results showed a high percentage of drug release. Additionally, an MTT assay was performed on the formulation of Capecitabine-loaded nanoparticles to assess the percentage of inhibition on the Caco-2 cell line, revealing a high percentage of inhibition at 20 mM of Capecitabine. Stability studies indicated that the formulation is fairly stable under storage conditions.

Conclusion: The development of polymeric nanoparticles that can release their payload in response to specific triggers allows for even more precise control over drug release, tailored to the physiological conditions of the target site.