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

Inspired\nby the intricate cellular morphology and the discoid shape\nof red blood cells (RBCs), biomimetic tricompartmental microcarriers\n(TCM) with controlled release profiles were engineered using an electrohydrodynamic-<i>co</i>-jetting technique for efficient management of Parkinson’s\ndisease (PD). While jetting, Levodopa (LD), CD (Carbidopa), and ENT\n(Entacapone) (3 PD drugs) were directly encapsulated in the three\nindividual compartments of the TCM used for oral administration. The\noptimal shape and controlled release profiles were obtained by employing\nthe Taguchi orthogonal L9 design-of-experiment approach by systematically\nvarying the processing parameters, i.e., solvent ratio, polymer concentration,\nand flow rate. The “smaller-the-better” norm for the\nS/N ratio demonstrated the solvent ratio (DMF content) and polymer\nconcentration as the most influential parameters in ensuring the RBC\nshape and controlling the release of drugs. Analysis of variance and\nresponse surface methodology approach provided insights into the optimal\ninfluence of control factors on the response variables. Confirmation\nexperiments further validated the optimized microparticles (<i>P</i><sub>optimized</sub>), demonstrating an error of only ∼0.13%\nin aspect ratio deviation (AR<sub>DEV</sub>) and ∼19% (within\nthe tolerance limit) in release factor (RF) from the predicted experiment.\nMoreover, <i>P</i><sub>optimized</sub> exhibits ∼100%\nencapsulation efficiency of all three PD drugs, with the cumulative\nrelease of ∼100% LD, ∼97% CD, and ∼65% ENT within\n5 h of the <i>in vitro</i> study. In addition, <i>in\nvivo</i> studies such as pharmacokinetics (using healthy rats)\nand pharmacodynamics [using the MPTP (methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-injected\nPD-induced mice model] showed that the TCM can effectively control\nthe release of LD (primary drug) for a prolonged period, thereby promising\nsustained drug delivery and improved therapeutics outcomes.