In vitro and in vivo suppression of cellular activity by guanidinoethyl disulfide released from hydrogel microspheres composed of partially oxidized hyaluronan and gelatin

Abstract

This paper describes the preparation of oxidized hyaluronan crosslinked gelatin microspheres for drug delivery. Microspheres were prepared by a modified water-in-oil-emulsion crosslinking method, where 3-dimensional crosslinked hydrogel microspheres formed in the absence of any extraneous crosslinker. SEM analyses of the microspheres showed rough surfaces in their dried state with an average diameter of 90 µm. Lyophilization of fully-swollen microspheres revealed a highly porous structure. Guanidinoethyl disulfide (GED) was used as a model drug for incorporation into the microspheres; encapsulation of GED was confirmed by HPLC. There was an inverse correlation between the diameters of the microspheres with their GED loading. Macrophage was used as a model cell to evaluate the in vitro efficacy of GED release from the microspheres. The in vivo efficacy of the microspheres was further validated in a mouse full-thickness transcutaneous dermal wound model through suppression of cell infiltration.

Repair of Chondral Defects With Allogenous Chondrocyte‐Seeded Hyaluronan/Collagen II Microspheres in a Rabbit Model

“…However, the poor mechanical properties of HA have prevented this unique biomaterial from being used for microspheres in a watery phase for a number of practical applications, such as those for long on-site duration. In the past, HA microspheres were typically prepared either by solvent evaporations from a water-in-oil emulsion or by spray-drying methods (11,12). The organic solvents and deoiling processes used in these methods could impede the biocompatibility of the microspheres and, thus, limit their use to encapsulate live cells or tissues and provide support for their growth.…”

Microfluidic formation of monodispersed spherical microgels composed of triple‐network crosslinking

“…For comparison, 3XN MPs were also prepared by a conventional bulk in‐emulsion‐crosslinking method previously described by us 3. In brief, aqueous Teleostean and CEC solutions (0.25 mL each) were mixed with 0.5 mL of an aqueous Odex solution.…”

“…Hydrogels are hydrophilic three‐dimensional polymer networks, crosslinked chemically and/or physically, capable of retaining a large amount of water 1, 2. The potentials of utilizing spherical hydrogel microparticles (MPs), or microgels as delivery vehicles for small molecules, macromolecules, and cells have been explored 3–5. By tailoring the properties of MPs, both the release‐rate and release‐profile of drug molecules can be optimized to for specific applications.…”

Understanding the in situ crosslinked gelatin hydrogel

“…Inci et al have recently investigated oxidized dextran crosslinked gelatin hydrogels loaded with hydroxyapatite as a scaffold for bone tissue engineering with an appreciable elastic modulus with interconnected porosity . In‐depth studies by Weng et al on the in vitro and in vivo responses of gelatin‐oxidized hyaluronan crosslinked hydrogels showed promising results . Balakrishnan et al have investigated gelatin crosslinked by oxidized CMC (OCMC) aided by borax for cartilage regeneration …”