Biomimetic Approach for Optimal Designing of the Shape and Controlled Release of Therapeutics from Tricompartmental Microcarriers for Managing Parkinson’s Disease

Inspired by the intricate cellular morphology and the discoid shape of red blood cells (RBCs), biomimetic tricompartmental microcarriers (TCM) with controlled release profiles were engineered using an electrohydrodynamic-<i>co</i>-jetting technique for efficient management of Parkinson's disease (PD). While jetting, Levodopa (LD), CD (Carbidopa), and ENT (Entacapone) (3 PD drugs) were directly encapsulated in the three individual compartments of the TCM used for oral administration. The optimal shape and controlled release profiles were obtained by employing the Taguchi orthogonal L9 design-of-experiment approach by systematically varying the processing parameters, i.e., solvent ratio, polymer concentration, and flow rate. The "smaller-the-better" norm for the S/N ratio demonstrated the solvent ratio (DMF content) and polymer concentration as the most influential parameters in ensuring the RBC shape and controlling the release of drugs. Analysis of variance and response surface methodology approach provided insights into the optimal influence of control factors on the response variables. Confirmation experiments further validated the optimized microparticles (<i>P</i>_optimized), demonstrating an error of only ∼0.13% in aspect ratio deviation (AR_DEV) and ∼19% (within the tolerance limit) in release factor (RF) from the predicted experiment. Moreover, <i>P</i>_optimized exhibits ∼100% encapsulation efficiency of all three PD drugs, with the cumulative release of ∼100% LD, ∼97% CD, and ∼65% ENT within 5 h of the <i>in vitro</i> study. In addition, <i>in vivo</i> studies such as pharmacokinetics (using healthy rats) and pharmacodynamics [using the MPTP (methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-injected PD-induced mice model] showed that the TCM can effectively control the release of LD (primary drug) for a prolonged period, thereby promising sustained drug delivery and improved therapeutics outcomes.