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Purpose <p>The study aims to develop and optimize a long-acting injectable formulation of Rasagiline Mesylate (RM) using poly(D, L-lactide-co-glycolide) (PLGA) microspheres for sustained management of Parkinson’s disease. RM, a selective monoamine oxidase-B (MAO-B) inhibitor is associated with controlling major symptoms such as muscle rigidity and bradykinesia. However, its oral formulation possesses drawbacks, including low bioavailability (~ 35%) and short elimination half-life (~ 1.5-3&#xa0;h).</p> Methods <p>To overcome these challenges associated with oral formulations, RM-loaded PLGA microspheres were fabricated using an oil-in-water (O/W) emulsion-solvent evaporation technique. Central Composite Design (CCD) was used for the optimization of microspheres by varying critical formulation parameters, including polymer-to-drug ratio, surfactant concentration, and stirring speed.</p> Results <p>The optimized formulation demonstrated a product yield of 82.07%, particle size of 18.199&#xa0;μm, and an entrapment efficiency of 71.69%. Morphological analysis by optical and Scanning Electron Microscopy (SEM) confirmed the spherical shape and size uniformity of the microspheres ideal for subcutaneous delivery. The incorporation of NaCl into the formulation enhanced entrapment efficiency by 6% and drug loading by 0.5%, while reducing the initial burst release by 2%. In vitro release studies showed sustained release for over two weeks, best fitted by zero-order kinetics. Furthermore, neuroprotection studies demonstrated prominent effects in the LPS-induced neuroinflammatory model, with PLGA microspheres exhibiting an IC<sub>50</sub> of 43.56&#xa0;µg/ml, and pure RM exhibited negligible cytotoxicity even at concentrations exceeding 1000&#xa0;µg/ml.</p> Conclusion <p>These findings demonstrate that RM-loaded PLGA microspheres represent a promising long-acting parenteral therapy with neuroprotective benefits for Parkinson’s disease management.</p> Graphical Abstract <p></p>

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Design, Optimization and In Vitro Neuroprotective Assessment of Rasagiline Mesylate-loaded PLGA Microspheres for the Parkinson’s Disease Management

  • 期刊论文

  • 发表日期：

    2026年3月23日

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  • Namrata Chaudhari,
  • Hrishikesh Khude,
  • Rohan Pai

摘要

Purpose

The study aims to develop and optimize a long-acting injectable formulation of Rasagiline Mesylate (RM) using poly(D, L-lactide-co-glycolide) (PLGA) microspheres for sustained management of Parkinson’s disease. RM, a selective monoamine oxidase-B (MAO-B) inhibitor is associated with controlling major symptoms such as muscle rigidity and bradykinesia. However, its oral formulation possesses drawbacks, including low bioavailability (~ 35%) and short elimination half-life (~ 1.5-3 h).

Methods

To overcome these challenges associated with oral formulations, RM-loaded PLGA microspheres were fabricated using an oil-in-water (O/W) emulsion-solvent evaporation technique. Central Composite Design (CCD) was used for the optimization of microspheres by varying critical formulation parameters, including polymer-to-drug ratio, surfactant concentration, and stirring speed.

Results

The optimized formulation demonstrated a product yield of 82.07%, particle size of 18.199 μm, and an entrapment efficiency of 71.69%. Morphological analysis by optical and Scanning Electron Microscopy (SEM) confirmed the spherical shape and size uniformity of the microspheres ideal for subcutaneous delivery. The incorporation of NaCl into the formulation enhanced entrapment efficiency by 6% and drug loading by 0.5%, while reducing the initial burst release by 2%. In vitro release studies showed sustained release for over two weeks, best fitted by zero-order kinetics. Furthermore, neuroprotection studies demonstrated prominent effects in the LPS-induced neuroinflammatory model, with PLGA microspheres exhibiting an IC50 of 43.56 µg/ml, and pure RM exhibited negligible cytotoxicity even at concentrations exceeding 1000 µg/ml.

Conclusion

These findings demonstrate that RM-loaded PLGA microspheres represent a promising long-acting parenteral therapy with neuroprotective benefits for Parkinson’s disease management.

Graphical Abstract