Dose-effect relationship of copolymer on enhancing aqueous lubrication of a hybrid osteoarthritis drug delivery nanocarrier.

Developing stimulus-responsive properties of drug delivery nanocarriers combined with enhanced joint lubrication is an effective synergistic strategy for treating osteoarthritis. Poly(N-isopropylacrylamide) (PNIPAm) is a typical thermo-responsive polymer, which can achieve drug delivery by transition from swollen state to collapsed state. However, undesired transition temperature, limited drug loading capacity, and weakened mechanical properties in joint present obstacles to use as drug delivery nanocarriers. In this work, we demonstrate dose-effect relationship between the PNIPAm-based copolymer and nanoscale metal-organic frameworks on enhancing both aqueous lubrication and drug delivery performance of a hybrid osteoarthritis (OA) nanocarrier. A series of NIPAm and poly(ethylene glycol)methacrylate (PEGMa) copolymer microgels with different feeding content are optimized to grow on the surface of MIL-101(Cr) nanoparticles via one-pot soap-free emulsion copolymerization method. By changing the feeding mass ratio of NIPAm and PEGMa, MIL-101(Cr)@P(NIPAm-g-PEGMa _x ) (x = 0, 1, 2, 3, and 4, named MPNP _x ) hybrids can ameliorate the lower critical solution temperature to match with OA and enhance the aqueous lubrication performance. Among the as-synthesized hybrids, MPNP ₃ hybrids manifested the notable enhanced thermo-responsive tribological performance due to the synergistic effect of "hydration lubrication" and "ball-bearing" function of the optimized copolymer microgel layer on the surface of metal-organic frameworks (MOFs). Anti-inflammatory drug loading is enabled by the high surface area and porosity of the MOFs, and the MPNP ₃ drug delivery nanocarriers achieve thermo-responsive release in vitro. Our work establishes the dose-effect relationship between thermo-responsive NIPAm and hydrophilic PEGMa of the copolymer grown on the surface of MOFs, providing valuable insights for improving the versatility of stimuli-responsive for biomedical application.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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