Development and evaluation of sustained-release clonidine-loaded PLGA microparticles

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Polymer Chemistry

Background:

• Sustained intra-articular drug delivery is crucial for managing joint conditions.
• Poly(lactic-co-glycolic) acid (PLGA) is a widely used biodegradable polymer for drug encapsulation.
• Achieving long-term, controlled release of hydrophilic drugs remains a challenge.

Purpose of the Study:

• To encapsulate clonidine, a small hydrophilic molecule, into PLGA microparticles.
• To achieve sustained intra-articular release of clonidine for over one month.
• To optimize microparticle formulation for efficient encapsulation and desired particle size.

Main Methods:

• Utilized a double emulsion (w(1)/o/w(2)) solvent evaporation method for microparticle preparation.
• Systematically modulated parameters including polymer molecular weight, phase volumes, drug loading, and surfactant concentration.
• Employed blends of PLGA and PLGA-PEG copolymers, adjusting pH for optimal encapsulation efficiency.

Main Results:

• Successfully prepared PLGA microparticles with clonidine, targeting a mean size of approximately 30 μm.
• Physico-chemical characterization included DSC, PXRD, and SEM to assess microparticle properties.
• In vitro dissolution studies demonstrated controlled release of clonidine for up to 30 days with optimized formulations.

Conclusions:

• Developed PLGA microparticle formulations capable of sustained intra-articular clonidine release exceeding one month.
• Diffusion was identified as the primary drug release mechanism in the initial stages.
• The study highlights the potential of optimized PLGA microparticles for long-term intra-articular therapy.