Simultaneous release of melatonin and methylprednisolone from an injectable in situ self‐crosslinked hydrogel/microparticle system for cartilage tissue engineering

Abstract

Recently, injectable hydrogel/microparticle systems have so considered for tissue engineering and regenerative medicine. In this study, we produced an injectable in situ self-crosslinked hydrogel/microparticle system for simultaneous dual drug delivery. First, melatonin conjugated chitosan microparticle loaded with methylprednisolone (MCC-MP) microparticle was fabricated by the covalent linkage of melatonin to chitosan by N-hydroxysuccinimide (NHS)1-Ethyl-3-(3-dimethylamino propyl)-carbodiimide (EDC) followed by an ionic gelation of MCC and MP using tripolyphosphate (TPP). Second, the hydrogel was prepared by the connection between the aldehyde group of alginate oxide (AD) and the amine group belonging to carboxymethyl chitosan (CMC) via Schiff base reaction. Finally, microparticle was incorporated into the AD-CMC hydrogel to produce a hydrogel/microparticle system. Hydrogel/microparticle was assessed by many techniques including microscopy, spectroscopy, particle size measurements, mechanical analysis, injectability, rheological analyses to ascertain hydrogel/microparticle properties. The biological assays of mesenchymal stem cells (MSCs) culture, 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), acridine orange/propidium iodide (AO/PI), and 4, 6-diamidino-2-phenylindole (DAPI) to assess cell viability and dimethylmethylene blue (DMMB) to evaluate proteoglycan content were done. The release profiles of melatonin and MP showed acceptable release after 60 and 20 days, respectively. The hydrogel/microparticle system has the ability to sustain cells alive. A higher rate of proteoglycan content was observed in hydrogel/microparticle as compared with hydrogel. With appropriate biocompatibility and adequate properties, this system can be a proper alternative for cartilage tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1932-1940, 2018.

Hydrogel as a Biomaterial for Bone Tissue Engineering: A Review

“…The water-holding capacity of hydrogel samples was determined through a centrifugation method [ 100 ]. The encapsulation efficiency can be measured by different materials such as spectrophotometer or high-performance liquid chromatography (HPLC) according to the different properties of the entrapped drug, which is also an important physical property of hydrogel [ 101 ].…”

“…Cell growth and proliferation can be quantified by MTT (tetrazolium salt, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay. AO/PI (acridine orange/propidium iodide) staining, DAPI (4,6-diamidino-2-phenylindole) staining, and resazurin assay are also useful methods [ 101 ]. Cell growth was also evaluated at protein levels by analysis of the biosynthesis of the ECM, stained with toluidine blue dye, and observed under an inverted microscope [ 106 ].…”

Cartilage regeneration with dual‐drug‐releasing injectable hydrogel/microparticle system: In vitro and in vivo study

“…OA and CMC were synthesized according to our previous reports (Naghizadeh et al, 2018a(Naghizadeh et al, , 2018b. To synthesis OA, sodium metaperiodate (1 g/ml) solution was added to the sodium alginate dispersion in ethanol (0.1 g/ml) overnight in the dark.…”

“…Then, 60 g monochloroacetic acid was added to the mixture. At the end, the hydrogel was made through a Schiff base reaction (Naghizadeh et al, 2018a(Naghizadeh et al, , 2018b.…”

Pharmacokinetic Profile and Anti-Adhesive Effect of Oxaliplatin-PLGA Microparticle-Loaded Hydrogels in Rats for Colorectal Cancer Treatment

“…However, pharmacokinetic evaluation of oxaliplatin-loaded HC hydrogels was not carried out. Several reports of microparticles-loaded hydrogels in various drug delivery system showed controlled drug release for over a prolonged period [19,20]. Therefore, to provide an adequate anti-adhesion barrier effect after cytoreductive surgery and deliver intraperitoneal chemotherapy, oxaliplatin-loaded PLGA microparticles were prepared, characterized, and loaded into HC hydrogels.…”