Design of Protein‐Releasing Chitosan Channels

Abstract

After traumatic injury to the spinal cord, the neural tissue degenerates, resulting in lost function below the site of injury. Promoting axonal regeneration after injury remains a challenge; however, guidance channels have demonstrated some success when combined with cellular and protein therapies. One of the limitations of current guidance channels is the inability to deliver therapeutically relevant molecules in situ, within the guidance channel, to enhance regeneration. In an effort to provide a system for local and sustained drug release, poly(lactide-co-glycolide) (PLGA) microspheres were embedded into chitosan guidance channels by a novel spin-coating technique. The method was designed to create guidance channels with the appropriate dimensions for implantation into the spinal cord, with special attention paid to the wall thickness. The release and bioactivity of a model protein, alkaline phosphatase, was followed from the channels and compared to those from free-floating microspheres over a 90-day period. Since chitosan formulations often require the use of acidic solutions, careful attention was paid to redesign the process to minimize exposure of PLGA microspheres to acid. This was achieved as demonstrated by release and bioactivity data where alkaline phosphatase released from chitosan/microsphere channels followed a profile and bioactivity similar to those of free floating microspheres.

Combination therapy of stem cell derived neural progenitors and drug delivery of anti-inhibitory molecules for spinal cord injury

“…PLGA microspheres, with a 50:50 lactic acid to glycolic acid ratio, were fabricated using a water in oil in water double emulsion solvent evaporation technique [53]. PLGA (10% w/v, intrinsic vis.…”

Sustained dual drug delivery of anti-inhibitory molecules for treatment of spinal cord injury

“…The ability to deliver active drugs to the injury using an implanted biomaterial scaffold may provide an improved alternative drug delivery method. PLGA microspheres were chosen to release the NEP1-40 peptide for their well-established formation methods, which allow for tunable control over the release rate and a longer release period [36, 44, 71]. The release rate is dependent upon the rate of hydrolytic degradation of the PLGA microspheres, which can be controlled by altering the ratio of lactic acid to glycolic acid, the intrinsic viscosity of the polymer (related to the molecular weight), or by changing formation conditions.…”

“…PLGA microspheres, with a 50:50 lactic acid to glycolic acid ratio, were fabricated using a water in oil in water double emulsion solvent evaporation technique [36]. PLGA (10% w/v, intrinsic vis.…”

Current tissue engineering and novel therapeutic approaches to axonal regeneration following spinal cord injury using polymer scaffolds

“…Alternatively, as shown in chitosan scaffolds (Fig. 10), the spheres can be localized directly to the channel wall by centrifugation (spin-coating) techniques (Kim et al, 2008). Nanoshells may be useful in the delivery of hydrophobic drugs from scaffolds.…”

“…(C) Scanning electron microscopy shows microspheres (arrowheads) embedded by the secondary chitosan coating. Figure from Kim et al (2008) with permission.…”