Polymer Micelle Cross-Linking for Stable Drug Delivery

The patent applies preliminary action by performing cross-linking of polymer chains in the micellar core before drug administration. This pre-cross-linking stabilizes the micelle structure against disintegration and prevents rapid drug diffusion, while still allowing the micelle to maintain its ability to load and release drugs in a controlled manner after administration.

The patent introduces an intermediary approach by using a two-stage process: first cross-linking the polymer chains to stabilize the carrier structure, then incorporating drugs through covalent bonding to the cross-linked network. This intermediary cross-linked structure prevents both carrier disintegration and rapid drug diffusion, as the covalent bonds hold drugs firmly while the cross-linked network maintains structural integrity.

The patent applies segmentation by dividing the drug-polymer conjugation process into two independent stages: first, cross-linking the polymer chains to form a stable network structure; second, incorporating drugs through covalent bonding to this pre-formed cross-linked network. This segmentation simplifies the overall process compared to direct covalent bonding during polymer synthesis, as each stage can be optimized independently and the cross-linked structure provides a stable platform for drug incorporation.

The patent applies beforehand cushioning by cross-linking the polymer chains in the micellar core before subjecting the formulation to aggressive processing like freeze-drying. This pre-cross-linking creates a robust network structure that cushions and protects the micelle properties during the stress of freeze-drying, preventing degradation of micelle morphology and function while still achieving long-term storage stability.