Macromolecular Therapeutics: Development and Delivery Engineering

Macromolecular therapeutics have been developed to improve the efficacy and safety profile of varied therapeutic agents for different diseases more than 50 years ago. N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers as a drug delivery platform have been extensively studied and applied in the clinical trials. Recently, the application of HPMA copolymers in the treatment of noncancerous diseases such as infectious diseases, musculoskeletal diseases, and traumatic brain injury has also been explored widely. In this chapter, different formulations of macromolecular therapeutics will be discussed. The design principles illustrated in the development of HPMA copolymer drug conjugates are also valid for other hydrophilic polymers, and they will be the principal focus of our discussion. The linker chemistry of the HPMA copolymer drug conjugates and its fine tuning will be discussed. Active targeting of HPMA copolymers based on targeting moieties and passively targeting HPMA copolymers based on the enhanced permeability and retention effect for cancer disease and extravasation through leaky vasculature and subsequent inflammatory cell-mediated sequestration mechanism for inflammation disease will be discussed. The most recent macromolecular prodrug-based thermoresponsive hydrogels designed for local injection to provide extended release with minimized systemic distribution will also be discussed in this chapter.