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An Aqueous Self-Assembly Method to Fabricate Degradable Covalently Cross-Linked Microgels

McMaster researchers have developed a method of preparing monodisperse degradable gel-based nanoparticles based on thermoresponsive polymers (e.g. poly(N-isopropylacryalmide), PNIPAM, or poly(oligoethylene glycol methacrylate, POEGMA)) for use in a wide range of medical and other applications.
An Aqueous Self-Assembly Method to Fabricate Degradable Covalently Cross-Linked Microgels

Figure - Microgel suspension before and after acid treatment (1M HCL, 2 hours)

Abstract

McMaster researchers have developed a method of preparing monodisperse degradable gel-based nanoparticles based on thermoresponsive polymers (e.g. poly(N-isopropylacryalmide), PNIPAM, or poly(oligoethylene glycol methacrylate, POEGMA)) for use in a wide range of medical and other applications. Conventional thermally responsive microgels are non-degradable and cannot be cleared renally. Consequently, these materials are likely to accumulate in vivo, leading to potential chronic toxicity issues and a strong unlikelihood of any ultimate approval of such materials for clinical use.

In the current method, McMaster researchers have synthesized microgels by first using controlled polymerization to create linear polymer precursors with molecular weights below the renal filtration limit. These precursor polymers are then self-assembled in water (without any additional reagents) to form hydrazone crosslinked microgels that can undergo controlled degradation back into the precursor polymers over time, facilitating clearance and thus avoiding the potential for toxicity. Functionalization of the precursor polymers can additionally introduce pH-responsiveness or glucose-responsiveness to the microgel, with the smart responses achieved similar to conventional precipitation-based microgels. The microgels can also be lyophilized and redispersed without any change in colloidal stability or particle size and exhibit no significant cytotoxicity in vitro. Microgels fabricated using this approach may facilitate translation of the attractive properties of such microgels in vivo without the concerns regarding clearance that exist with other microgels.

Applications

  • Drug Delivery- Making microgels that are degradable and clearable solves one of the key barriers to their practical use in drug delivery.
  • Biomedical Applications- Mechanical supports for soft tissue, biological lubricants at joints, spinal column structuring agents.
  • Biosensors & Molecular Probes- Attachment of cognate ligands of target entities to microgel matrix may enable use as MRI and CT contrast agents.
  • Enhanced Oil Recovery- Used to plug rock crevices, thus reducing the pressure required to pump out oil.
  • Environmental Biosensing- Specific biomarkers can be covalently tagged or embedded within microgel matrix to detect target pathogen(s).

Advantages

  • Microgels are degradable hydrolytically, with enhanced degradation rates when exposed to mildly acidic conditions (e.g. endosomes).
  • Renal clearance of degradation products possible.

Tech ID

15-046

Inventors

D. Sivakumaran
T. Hoare

Patent Status

US Provisional Application filed

Stage of Research

Assessing drug release properties, cytotoxicity and bioaccumulation in vivo. Studies aimed at improving formulation also in progress.

Contact

Sunita Asrani
Business Development Manager
905-525-9140 ext. 28641
asranis@mcmaster.ca 
http://milo.mcmaster.ca