Optimization of PLG microspheres for tailored drug release

Area of Science:

• Biomaterials Science
• Pharmaceutical Sciences
• Drug Delivery Systems

Background:

• Microcapsules offer potential for controlled therapeutic drug release.
• Poly(lactic-co-glycolic acid) (PLG) microcapsules are a validated system for drug delivery.
• Tailoring drug release profiles is crucial for optimizing therapeutic efficacy.

Purpose of the Study:

• To develop an inverse design algorithm for creating tailored drug release profiles from microcapsules.
• To optimize combinations of microcapsule populations (building blocks) for specific release histories.
• To validate the mathematical model for drug release from PLG microcapsules with varying polymer molecular weights.

Main Methods:

• Utilized an inverse design algorithm based on a validated mathematical model for drug release from PLG microcapsules.
• Employed "building blocks" comprising microcapsule populations with varying mean diameter, polydispersity, and polymer molecular weight.
• Applied constrained optimization to a basis of six microcapsule systems to fit a prescribed release profile.

Main Results:

• The inverse design algorithm successfully predicted optimal microcapsule combinations for desired release profiles.
• Experimental validation demonstrated excellent agreement between predicted and measured drug release, with correlation coefficients > 0.98.
• A triple-pulse drug release design was successfully demonstrated, showcasing the method's capability.

Conclusions:

• The developed inverse design algorithm provides a powerful tool for engineering tailored drug release from microcapsules.
• This approach allows for precise control over drug release kinetics by optimizing microcapsule characteristics.
• The method holds significant promise for advancing personalized medicine and improving therapeutic outcomes.