3D-Printed Drug/Cell Carrier Enabling Effective Release of Cyclosporin a for Xenogeneic Cell-Based Therapy

Abstract

Systemic administration of the immunosuppressive drug cyclosporin A (CsA) is frequently associated with a number of side effects; therefore, sometimes it cannot be applied in sufficient dosage after allogeneic or xenogeneic cell transplantation. Local delivery is a possible solution to this problem. We used 3D printing to develop a CsA-loaded 3D drug carrier for the purpose of local and sustained delivery of CsA. The carrier is a hybrid of CsA-poly(lactic-co-glycolic acid) (PLGA) microsphere-loaded hydrogel and a polymeric framework so that external force can be endured under physiological conditions. The expression of cytokines, which are secreted by spleen cells activated by Con A, and which are related to immune rejection, was significantly decreased in vitro by the released CsA from the drug carrier. Drug carriers seeded with xenogeneic cells (human lung fibroblast) were subcutaneously implanted into the BALB/c mouse. As a result, T-cell-mediated rejection was also significantly suppressed for 4 weeks. These results show that the developed 3D drug carrier can be used as an effective xenogeneic cell delivery system with controllable immunosuppressive drugs for cell-based therapy.

Tissue Engineered Bio‐Blood‐Vessels Constructed Using a Tissue‐Specific Bioink and 3D Coaxial Cell Printing Technique: A Novel Therapy for Ischemic Disease

“…[29] Briefly, 120 mg poly(d,llactic-co-glycolic) acid (Cat.no. 430471, Sigma-Aldrich) and 12 mg atorvastatin calcium salted trihydrate (Cat.no.…”

Polysaccharide 3D Printing for Drug Delivery Applications

“…As discussed with CS, to control the release of an API, the active ingredient is often encapsulated in polymeric nanoparticles, before being introduced in the printing ink. For example, Song et al incorporated cyclosporin A-loaded PLGA microspheres in an Alg hydrogel and achieved a sustained release over 4 weeks [178], while Gao et al observed a sustained release over a month when atorvastatin-loaded PLGA nanoparticles were inserted in a hybrid bioink containing 2% w/w Alg and 3% w/w vascular-tissue derived decellularized extracellular matrix [179]. In the same vein, Liu et al developed an alginate/collagen hydrogel containing HAp nanoparticles and enrofloxacin-loaded PCL microspheres, for the printing of a long-term antimicrobial scaffold [180].…”

Advanced fabrication approaches to controlled delivery systems for epilepsy treatment

“…To note, although the alginate-PLGA tubes show high mechanical strength, incorporation of drugs decreases the overall mechanical properties and thus would need minor adjustments to improve the strength to a suitable level for implant-based applications. On the other hand, Song et al [59] were able to achieve proper mechanical properties by combing a drug-loaded PLGA hydrogel with a PCL-based polymeric framework for extra stability. This carrier allowed for sustained local delivery of cyclosporin A and a resulting reduction in a xenogeneic cell-based immune response.…”