Kinetic modelling and in vitro release mechanism of levodopa from sporopollenin-based microcapsules in human blood plasma

Abstract

Levodopa (LD) remains the most effective therapy for Parkinson's disease; however, its short plasma half-life necessitates frequent dosing and contributes to fluctuating drug levels and motor complications. In this study, we systematically investigated the in vitro release behaviour of LD from sporopollenin exine microcapsules (SECs) in a clinically relevant biological medium, human blood plasma, and applied kinetic modelling to elucidate the governing release mechanism. LD-loaded sporopollenin microcapsules (0.5 g) were prepared by vacuum-assisted, pH-triggered precipitation and incubated in human plasma at 37 °C under moderate agitation (50 rpm). Release experiments were conducted over 12 h, with sequential sampling and medium replacement to maintain constant volume and sink conditions. LD concentrations were quantified by UV-Vis spectrophotometry using validated plasma-matched calibration curves. The release profile exhibited a reproducible biphasic pattern, characterised by a rapid initial phase within the first 30 min, followed by a prolonged and stable release phase extending to 12 h. Despite low fractional release, the system rapidly established a therapeutically relevant equilibrium LD concentration in plasma, indicative of reservoir-controlled drug availability rather than depletion-driven release. Kinetic modelling demonstrated that the Higuchi model provided the best fit to the concentration-time data (R² = 0.9955 ± 0.0008). In contrast, the Korsmeyer–Peppas model yielded a low release exponent (n = 0.209 ± 0.002), consistent with diffusion-dominated, Fickian transport. Peppas–Sahlin analysis further confirmed the predominance of diffusional mechanisms, with minimal contribution from matrix relaxation. These findings demonstrate that SECs function as stable, reservoir-type carriers that provide both rapid initial LD availability and sustained plasma concentrations under physiologically relevant conditions. This work, to our knowledge, represents the first detailed kinetic analysis of LD release from SECs in human blood plasma and highlights the potential of this natural biopolymer as a bio-regulated platform for improved LD delivery in Parkinson's disease.