ArticleRheumatology international2025
In vitro development and evaluation of chitosan-cellulose nanocrystal microspheres for controlled dexamethasone delivery in rheumatoid arthritis.
Article in Rheumatology international, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Systemic glucocorticoids are effective in rheumatoid arthritis, but long-term exposure carries dose-dependent risks. We developed a "nano-in-micro" platform in which cellulose nanocrystals (CNCs; <100 nm) are embedded within polymeric microspheres (about 100-400 μm) to modulate dexamethasone release while preserving drug identity and matrix integrity. Microsphere formulations varying in CNC and chitosan content were prepared and characterized at a fixed drug load. FT-IR and UV-Vis spectroscopy confirmed drug identity and assay linearity. Optical microscopy and SEM assessed particle size and morphology; CNCs were examined by TEM. Process yield, encapsulation efficiency (EE), equilibrium swelling, and cumulative drug release over 10 h were measured. Release data were fitted to zero-order, first-order, Higuchi, Hixson-Crowell, and Korsmeyer-Peppas models. Microspheres (predominantly 100-150 μm within a 100-400 μm design space) were produced with high process yields (approximately 85-89%) and moderate encapsulation efficiency (approximately 52-63%). Increasing cellulose nanocrystal (CNC) content reduced equilibrium swelling (from about 180% to about 150%) and slowed dexamethasone release over 10 h (from approximately 100% for chitosan-only to approximately 87% at the highest CNC loading). UV-Vis quantitation was highly linear (R² = 0.9876). Diffusion-based models best described release profiles (Higuchi, Korsmeyer-Peppas; R² ≥ 0.97), whereas first-order kinetics were comparatively stronger in the fastest-releasing, chitosan-rich formulations. Embedding CNCs within polymeric microspheres provides a controllable lever to tune swelling and diffusional pathways, enabling short-to-medium dexamethasone release profiles without compromising analytical identity or process robustness. The platform's reproducible yields and predictable CNC-dependent slowing of release support further optimization (e.g., cross-link density, medium conditions) and in vivo evaluation toward dosing concepts that minimize systemic glucocorticoid exposure. Clinical applicability has not yet been established; in vivo biocompatibility, pharmacokinetic, and efficacy studies-aligned with medicinal‑product guidance-are required before any translational claims can be made.
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