Trigger strategies

LLP-assisted local delivery of dmgs is realized via several strategies. In the first strategy, soluble LLPs are injected and their coacervation is triggered by the body temperature. Here, the dmg can be covalently attached to the ELP or it can just be mixed with the ELP. In another approach, crosslinked ELP depots containing a dmg can be produced and then implanted to generate a stable release of the dmg. 

This first strategy was used by Setton and coworkers to trigger the in situ formation of an ELP-based dmg depot for sustained release. Biodistribution studies of radiolabeled LLPs with a below body temperature were performed after intra-articular injection in rats [94]. Later, dmg depots of ELPs with covalently attached immunomodulator therapeutics [95] and anti-TNLa therapeutics [96] were created. Respectively, ELP[V-120] and ELP[V-60] biopolymers with a transition below body temperature were used in these studies. 

Tumor tissues overexpress matrix metalloproteinases (MMPs). A liposomal pDNA carrier (MEND) was developed containing PEG conjugated to lipid via a peptide linker that is a target sequence for MMPs. In this strategy, PEG is removed from the carrier via MMP-triggered cleavage [198]. Intravenous administration in... 

Oupicky D, Parker AL, Seymour LW (2002) Laterally stabilized complexes of DNA with linear reducible polycations strategy for triggered intracellular activation of DNA delivery vectors. J Am Chem Soc 124 8-9... 

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