Polyamine-salt aggregate assembly of capsules as responsive drug delivery vehicles

Responsive capsular delivery systems that can partly mimic the complexity of cellular systems hold great promise for the future of medicine. Simple self-assembled systems like liposomes are already in clinical use and others like polymeric micelles are under clinical trials. Unlike these self-assembled systems, the greater flexibility and versatility offered by template-based routes will likely drive the development of sophisticated capsules. The focus of this review is to introduce one such template-based route, which is based on polyamine-salt aggregate or 'PSA' assembly. The basic synthesis premise involves the assembly of cationic polymer (like poly-L-lysine) by ionic crosslinking with multivalent anionic salts (like citrate) into metastable templates for cargo encapsulation and shell material deposition. The technique offers several benefits: (i) the synthesis procedure involves simple mixing at ambient conditions, (ii) the capsule size is easy to control in the sub-100 nm to micron range, and (iii) a wide range of formulations is readily available with the use of different polymer, salt, cargo, and shell-forming precursors. In this review, the current state of this technique, the materials chemistry of the capsule assembly, and the demonstrated applications, including photothermal therapy, MRI contrast agent development and protease-responsive NIR imaging, will be discussed.