000041293 001__ 41293
000041293 005__ 20240125142327.0
000041293 0247_ $$2doi$$a10.6083/bpxhc41293
000041293 037__ $$aETD
000041293 041__ $$aeng
000041293 245__ $$aAn enzyme-responsive nanoplatform for preventing collagen degradation in dental tissues
000041293 260__ $$bOregon Health and Science University
000041293 269__ $$a2023-07-19
000041293 336__ $$aAbstract
000041293 520__ $$aThe collagen degradation mediated by host proteolytic enzymes, such as the metalloproteinases (MMPs), is strongly associated to the development of secondary caries at the restorative material-dental tissues interface and periodontal disease. While some potent MMP inhibitors have been identified, their incorporation in the dental biomaterials remains as a challenge due to chemical incompatibility, poor diffusion, and limited substantivity. Therefore, this study is aimed at developing an innovative MMP-responsive nanocarrier to serve as a delivery vehicle for enzyme inhibitors and promote their sustainable and on-demand release.


	newly designed nanocarrier is based on a micellar nanoparticle composed of a block-copolymer with MMP-9 recognizable/cleavable sequences. For the block-copolymer synthesis, the compounds (N-Benzyl)-5-norbornene-exo-2,3-dicarboximide and 1-{[(2S)-bicyclo[2.2.1]hept-5-en-2-ylcarbonyl]oxy}-2,5-pyrrolidinedione were synthesized. polymerization was catalyzed by a modified Grubbs catalyst. final block-copolymer was obtained via precipitation in cold methanol and centrifugation, and characterized by NMR spectroscopy.


The copolymer (50 mg/mL) was dissolved in an anhydrous mixture of dimethylformamide and dimethyl sulfoxide containing peptides with the amino acid sequence GPLGLAGGWGERDGS and N,N-Diisopropylethylamine (1:4:16 copolymer:peptide:DIPEA). After stirring for 27 hr, the solution was precipitated in cold methanol and centrifuged—the peptide-copolymer was characterized by NMR spectroscopy.


To form micelles, the block copolymer-peptide compound was first dissolved in DMSO and distilled water was added until reaching the critical micelle concentration (30% v/v aqueous). After 2 days of stirring, water was added until reaching 50% v/v aqueous. The final solution was transferred to dialysis tubing and placed in water. The buffer was exchanged 3x per day for 2 days, then the procedure was repeated once with Dulbecco’s phosphate-buffered saline solution.
 

The micelles were characterized by transmission electron microscopy after being concentrated. The responsivity to MMP-9 was tested by incubating the micelles in buffer for 24 hr at 37 °C, and further analyzed by TEM.
000041293 540__ $$fCC BY
000041293 542__ $$fIn copyright - single owner
000041293 650__ $$aChemistry$$016438
000041293 650__ $$aOral Health$$023251
000041293 650__ $$aPeptide Hydrolases$$023761
000041293 650__ $$aMatrix Metalloproteinases$$032691
000041293 650__ $$aDental Caries Susceptibility$$017486
000041293 650__ $$aPeriodontal Diseases$$023822
000041293 6531_ $$ammp
000041293 6531_ $$ananomicelles
000041293 6531_ $$ainhibition
000041293 6531_ $$acaries
000041293 6531_ $$agum disease
000041293 6531_ $$amicelles
000041293 691__ $$aSchool of Dentistry$$041368
000041293 692__ $$aDepartment of Integrative Biomedical and Diagnostic Sciences$$041418
000041293 7001_ $$aHuynh, Bao$$uOregon Health and Science University$$041354
000041293 711__ $$aResearch Week$$uOregon Health and Science University$$d2023
000041293 7201_ $$aFugolin, Ana P.P.$$7Personal
000041293 7201_ $$aRajasekaran, Sivashankari$$eCollaborator$$7Personal
000041293 8564_ $$90fec6a9a-fbe8-4051-b28b-1af7e7f6b25d$$s135305$$uhttps://digitalcollections.ohsu.edu/record/41293/files/ResearchWeek.2023.Huynh.Bao.pdf
000041293 980__ $$aResearch Week
000041293 981__ $$aPublished$$b2023-07-19