Multilayer capsules made of weak polyelectrolytes: a review on the preparation, functionalization and applications in drug delivery

Multilayer capsules have been of great interest for scientists and medical communities in multidisciplinary fields of research, such as drug delivery, sensing, biomedicine, theranostics and gene therapy. The most essential attributes of a drug delivery system are considered to be multi-functionality and stimuli responsiveness against a range of external and internal stimuli. Apart from the highly explored strong polyelectrolytes, weak polyelectrolytes offer great versatility with a highly controllable architecture, unique stimuli responsiveness and easy tuning of the properties for intracellular delivery of cargo. This review describes the progress in the preparation, functionalization and applications of capsules made of weak polyelectrolytes or their combination with biopolymers. The selection of a sacrificial template for capsule formation, the driving forces involved, the encapsulation of a variety of cargo and release based on different internal and external stimuli have also been addressed. We describe recent perspectives and obstacles of weak polyelectrolyte/biopolymer systems in applications such as therapeutics, biosensing, bioimaging, bioreactors, vaccination, tissue engineering and gene delivery. This review gives an emerging outlook on the advantages and unique responsiveness of weak polyelectrolyte based systems that can enable their widespread use in potential applications.