Sequential flash nanocomplexation and flash nanoprecipitation enables scalable assembly of doxorubicin-loaded
Yuanmuhuang Long1, Sachin V Kammula2, Yicheng Zhang3
1Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, United States of America; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States of America.
Abstract:
The study presents the sequential flash nanocomplexation (FNC)-flash nanoprecipitation (FNP) process as a scalable method for producing polymeric nanoparticles (NPs) with controlled encapsulation and release of doxorubicin (DOX). In the FNC step, DOX is first crosslinked with tannic acid (TA), then stabilized by human serum albumin (HSA) via hydrogen bonding, forming uniform DOX-TA-HSA nanocomplexes. The nanocomplexes are then encapsulated into poly(ethylene glycol)-b-poly(lactic acid-co-glycolic acid) (PEG-b-PLGA) dissolved in various water-miscible organic solvents through FNP. Solvent selection significantly influenced the release rate, with dimethyl sulfoxide (DMSO) enabling sustained release for up to two weeks. Additionally, the optimized process demonstrated excellent reproducibility and scalability, with minimal batch-to-batch variations. This NP assembly process is complemented by scalable purification with the tangential flow filtration (TFF) method, showing preserved size distribution and DOX release kinetics. This study underscores the technical advantages and translational potential of the FNC-FNP process for nanotherapeutic manufacturing.
