Preparation of PLGA nanoparticle/sodium alginate composites by pressurized Gas-eXpanded liquid technology for drug delivery applications

A dried, homogeneous porous composite containing poly(lactic-co-glycolic acid) nanoparticles (PLGA-NP) entrapped in a sodium alginate (SA) aerogel matrix was developed using the Pressurized Gas-eXpanded liquid Technology (PGX TEC ) and compared to the same material dried by lyophilization. The size and stability of PLGA-NP in all stages of the processes were studied using dynamic light scattering and Field Emission Scanning Electron Microscopy. The morphology of the composites was investigated using helium ion microscopy, and fluorescence confocal microscopy. A fluorescently labeled dextran analogue (Tetramethylrhodamine Dextran, TMRD) as model for macromolecular drugs was loaded onto PLGA-NP and processed into PGX TEC -processed and freeze-dried composites. The release kinetics of TMRD from composites were measured and compared with unprocessed PLGA-NP. The results revealed that the processing of PLGA-NP using the PGX TEC expanded the particles leading to porous structures that facilitate the release of encapsulated macromolecules. Both composites prepared by PGX TEC or lyophilisation showed an initial burst release of TMRD in HEPES buffer solution in the first 8 h, reaching up to 8 % and 22 %, respectively. The PGX TEC processed composite outperformed the lyophilized composite for the total cumulative TMRD release after 400 h reaching 100 % release, while the lyophilized composite reached a plateau of about 32.7 %. The results suggest that PGX TEC -processed PLGA-NP entrapped in a SA matrix forming a PLGA-NP/SA composite have potential for delivery of macromolecular drugs such as peptides and proteins. • PLGA nanoparticles/sodium alginate aerogel (PLGA-NP/SA) was developed using Pressurized Gas-eXpanded liquid Technology (PGX TEC ). • PLGA-NP expanded by PGX TEC to a porous structure facilitating loading and release of bioactives of high molecular weight. • The PGX TEC generated PLGA-NP/SA composites have potential to deliver macromolecules, such as proteins or peptides.