Stimuli responsiveness of recent biomacromolecular systems (concept to market): A review

Stimuli responsive delivery systems, also known as smart/intelligent drug delivery systems, are specialized delivery vehicles designed to provide spatiotemporal control over drug release at target sites in various diseased conditions, including tumor, inflammation and many others. Recent advances in the design and development of a wide variety of stimuli-responsive (pH, redox, enzyme, temperature) materials have resulted in their widespread use in drug delivery and tissue engineering. The aim of this review is to provide an insight of recent nanoparticulate drug delivery systems including polymeric nanoparticles, dendrimers, lipid-based nanoparticles and the design of new polymer-drug conjugates (PDCs), with a major emphasis on natural along with synthetic commercial polymers used in their construction. Special focus has been placed on stimuli-responsive polymeric materials, their preparation methods, and the design of novel single and multiple stimuli-responsive materials that can provide controlled drug release in response a specific stimulus. These stimuli-sensitive drug nanoparticulate systems have exhibited varying degrees of substitution with enhanced in vitro/in vivo release. However, in an attempt to further increase drug release, new dual and multi-stimuli based natural polymeric nanocarriers have been investigated which respond to a mixture of two or more signals and are awaiting clinical trials. The translation of biopolymeric directed stimuli-sensitive drug delivery systems in clinic demands a thorough knowledge of its mechanism and drug release pattern in order to produce affordable and patient friendly products.