Evaluation of Mass Spectrometry Compatible Reagents for Determining Small Molecule Loading in Poly(lactic acid)...

Area of Science:

• Materials Science
• Analytical Chemistry
• Pharmaceutical Sciences

Background:

• Poly(lactic acid) nanoparticles (PLA-NPs) are widely used drug delivery systems.
• Accurate quantification of encapsulated drugs is crucial for formulation development.
• Traditional methods for drug release from PLA-NPs can be cumbersome.

Purpose of the Study:

• To assess the efficacy of ammonium hydroxide, a mass spectrometry-friendly base, for hydrolyzing PLA-NPs.
• To evaluate the impact of nanoparticle formulation parameters on drug loading.
• To establish a simplified quantitative method for drug loading analysis in PLA-NPs.

Main Methods:

• Microfluidics was employed to generate a library of PLA-NPs with varied formulation parameters.
• Dynamic light scattering was used for nanoparticle characterization (size, PDI, zeta potential).
• Hydrophobic drugs were encapsulated, and their release was induced by base hydrolysis (NaOH or NH4OH) followed by LC-MS/MS quantification.

Main Results:

• Ammonium hydroxide demonstrated comparable efficacy to sodium hydroxide in releasing encapsulated hydrophobic drugs from PLA-NPs.
• The developed method using ammonium hydroxide is compatible with LC-MS/MS quantitative analysis.
• Nanoparticle formulation parameters, including flow rate ratio and surfactant type, significantly influenced NP characteristics and drug loading.

Conclusions:

• Ammonium hydroxide is an effective and mass spectrometry-friendly base for hydrolyzing PLA-NPs.
• This approach simplifies the quantitative analysis of drug loading in nanoparticle formulations.
• The findings enable more efficient evaluation of drug loading influenced by NP formulation parameters.