Enhanced ibuprofen loading capacity of chitosan nanoparticles for prolonged release: A comprehensive study

Objectives. Oral administration of ibuprofen often requires much higher doses than the necessary therapeutic dose due to the low solubility and first-pass metabolism of this anti-inflammatory drug. In order to improve its solubility and bioavailability, orally administered ibuprofen can be encapsulated into chitosan nanoparticles. The release of ibuprofen from chitosan nanoparticles can be pH-controlled to increase drug delivery efficiency when passing through the gastrointestinal tract. While ionic gelation provides versatile nanochitosan synthesis, the impact of the chitosan-to-tripolyphosphate (CS/TPP) ratio on encapsulation efficiency (EE) and loading capacity (LC) of the ibuprofen-loaded chitosan nanoparticles (IBU-CSNPs), as well as their release behavior under various pH conditions, remains unexplored. The study aims to determine the appropriate CS/TPP ratio for the highest EE and LC, as well as to evaluate the morphology, release behavior, and degradability of the IBU-CSNPs under optimal conditions.

Methods. The effect of CS/TPP ratio on the EE and LC of nanoparticle-loaded ibuprofen is studied by comparing the total and free concentrations of the drug and the weights of the CSNPs and IBU-CSNPs. To elucidate the characteristic properties of the IBU-CSNPs prepared at the optimal CS/TPP ratio, in-depth characterization was performed, including their morphology, chemical structure, crystallinity profile, in vitro degradation, and release behavior. The release profile of the IBU-CSNPs is studied under simulated gastric fluid (SGF), intestinal fluid (SIF), and sequential conditions of SGF and SIF.

Results. EE and LC were found to be significantly enhanced by an appropriate 1 : 1 mg/mg ratio, reaching 77.70 ± 0.65% and 46.62 ± 0.39%, respectively. The fabricated IBU-CSNPs exhibit a spherical shape with a uniform size distribution of approximately 50–60 nm and accelerated degradation compared to the unadulterated chitosan nanoparticles under simulated gastrointestinal conditions. The synthesized IBU-CSNPs demonstrate remarkable acid resistance by a minimal drug release of 9.44% in SGF after 3 h. However, a sustained release pattern in SIF achieves an equilibrium cumulative release of 94.51% over 5 days. The elaboration of drug release kinetics using the Kopcha and Korsmeyer–Peppas models suggests erosion-controlled release in SGF and diffusion-controlled release with swellable ability in SIF.

Conclusions. The results represent valuable insights into the formulation of pH-responsive IBU-CSNPs for the controlled delivery of ibuprofen via oral administration.

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