Dual Responsive Poly(N-vinylcaprolactam) Based Degradable Microgels for Drug Delivery

Abstract

Poly(N‐vinylcaprolactam)‐based biodegradable microgels are prepared for drug delivery application via precipitation polymerization using diacetone acrylamide (DAAM) and dimethyl itaconate (IADME) as comonomers. The microgel particles are subsequently crosslinked by addition of adipic acid dihydrazide, which reacts with the ketone groups of DAAM. Itaconic acid (IA) groups are generated by the hydrolysis of IADME units inside the microgels resulting into both pH and temperature sensitive microgel particles. Volume phase transition temperature of the obtained microgels is influenced by both IA content and pH of the surrounding medium. Due to the incorporation of hydrazone linkages, the microgels show degradation under acidic conditions. These microgels can effectively encapsulate doxorubicin (DOX) as a model drug and show low DOX leakage under physiological conditions while rapid DOX release is observed at low pH. The results of the cytotoxicity assay further display that the DOX‐loaded microgels exhibit effective antitumor activity against HeLa cells demonstrating their great potential as drug delivery carriers for cancer therapy.

Functional Microgels: Recent Advances in Their Biomedical Applications

“…A brief overview of these chemical methods is given here. Readers are referred to various other reviews and articles for detailed study …”

“…Agrawal et al designed temperature‐ and pH‐responsive PVCL/diacetone acrylamide (DAAM)/dimethyl itaconate (IADME) microgels via precipitation polymerization . During synthesis, adipic acid dihydrazide was added to generate hydrazone‐based crosslinking.…”

“…In general, microgels can be loaded with drugs using physical interactions such as electrostatic interaction, hydrophobic interaction, and hydrogen bonding . Furthermore, drug loading can also be achieved by redispersing the freeze‐dried microgels in drug solution.…”

“…Despite the extensive research on various nanosystems such as nanoparticles, liposomes, micelles, polymerosomes, and dendrimers, their widespread clinical use is still hampered due to premature drug release, shorter blood circulation time, insufficient renal clearance, insufficient in vivo biodistribution, lack of cytospecificity, and high toxicity . As compared to other nanosized counterparts, microgels, aqueous, 3D‐crosslinked, polymeric particles exhibit tunable size, functionalized porous network for encapsulation, and excellent biocompatibility .…”

“…Once the target site is reached, microgels can release the encapsulated drugs and bioactive molecules with the help of a number of stimuli‐responsive mechanisms. Based on their chemical design during synthesis or postmodification process, these functional microgels can respond to various stimuli such as temperature, pH, redox potential, magnetic field, enzymes, etc., and thus controlled drug release can be achieved. Additionally, microgels that can fully or partially degrade under the desired conditions further facilitate the release process and ensure better biocompatibility by renal clearance of the degraded by‐products …”