Systematic development and optimization of a microfluidic formulation protocol for liposomal azithromycin

Area of Science:

• Pharmaceutical Sciences
• Nanotechnology
• Cardiovascular Research

Background:

• Liposomal azithromycin (L-AZM) shows promise for treating cardiac injury post-myocardial infarction.
• Conventional thin film hydration (TFH) for L-AZM production faces scalability and reproducibility issues, hindering clinical translation.

Purpose of the Study:

• To optimize liposomal azithromycin (L-AZM) formulation using microfluidic nanoprecipitation for improved manufacturing and clinical applicability.
• To evaluate critical quality attributes (CQAs) of L-AZM produced via microfluidics compared to TFH.

Main Methods:

• Systematic optimization of microfluidic nanoprecipitation parameters (flow rate ratio, total flow rate).
• Formulation adjustment using DSPC:DSPG:Chol:AZM molar ratios.
• Evaluation of liposome size, polydispersity index (PDI), encapsulation efficiency, and leakage.
• Comparison of in vitro macrophage polarization activity between microfluidic and TFH methods.

Main Results:

• Optimal microfluidic parameters determined as 4:1 flow rate ratio and 10 mL/min total flow rate.
• An optimized formulation (DSPC:DSPG:Chol:AZM 1:1:1:0.5) exhibited reduced size and PDI compared to TFH.
• No significant difference in in vitro macrophage polarization activity was observed between the two formulation methods.

Conclusions:

• Microfluidic nanoprecipitation provides a reproducible and scalable method for producing L-AZM with enhanced quality attributes.
• The optimized L-AZM formulation is suitable for further preclinical development and potential clinical translation for myocardial infarction treatment.
• This study establishes a manufacturing pathway for advanced liposomal drug delivery systems.