In Situ Cross-Linkable High Molecular Weight Hyaluronan Bisphosphonate Conjugate for Localized Delivery and Cell-Specific Targeting: A Hydrogel Linked Prodrug Approach

摘要

In recent years considerable effort has been given to improve site specific biodistribution and time-controlled delivery of drugs to minimize undesired side effects and to improve the efficacy of the treatment.Most of the polymeric drug delivery systems are designed for intravenous administration on the basis of EPR (enhanced permeability retention) effect and include nanoparticles, dendrimers, liposomes, and polymeric micelles. An injectable hydrogel based delivery system has mainly been employed to deliver large protein based drugs such as growth factors and very recently was used for small molecule drugs such as doxorubicin and cisplatin. The incorporation of small molecule drugs limits the applicability due to their passive diffusion out of highly porous hydrogels. Polymer-drug conjugates, however, having a specific cell targeting ligand could be incorporated into an implantable drug delivery device and may provide precise dose control, high release efficiency, low toxicity, and cell specificity. This provides a platform to overcome disadvantages associated with conventional drug delivery systems by closely mimicking the natural cell targeting mechanism. The localized delivery of such drugs at the surgical resection site could open up new avenues to control tumor recurrence after removal of the tumor.