Three-Dimensional Printing of Curcumin-Loaded Biodegradable and Flexible Scaffold for Intracranial Therapy of Glioblastoma Multiforme

Abstract

A novel drug delivery system preventing Glioblastoma multiforme (GBM) recurrence after resection surgery is imperatively required to overcome the mechanical limitation of the current local drug delivery system and to offer personalised treatment options for GBM patients. In this study, 3D printed biodegradable flexible porous scaffolds were developed via Fused Deposition Modelling (FDM) three-dimensional (3D) printing technology for the local delivery of curcumin. The flexible porous scaffolds were 3D printed with various geometries containing 1, 3, 5, and 7% (w/w) of curcumin, respectively, using curcumin-loaded polycaprolactone (PCL) filaments. The scaffolds were characterised by a series of characterisation studies and in vitro studies were also performed including drug release study, scaffold degradation study, and cytotoxicity study. The curcumin-loaded PCL scaffolds displayed versatile spatiotemporal characteristics. The polymeric scaffolds obtained great mechanical flexibility with a low tensile modulus of less than 2 MPa, and 4 to 7-fold ultimate tensile strain, which can avoid the mechanical mismatch problem of commercially available GLIADEL wafer with a further improvement in surgical margin coverage. In vitro release profiles have demonstrated the sustained release patterns of curcumin with adjustable release amounts and durations up to 77 h. MTT study has demonstrated the great cytotoxic effect of curcumin-loaded scaffolds against the U87 human GBM cell line. Therefore, 3D printed curcumin-loaded scaffold has great promise to provide better GBM treatment options with its mechanical flexibility and customisability to match individual needs, preventing post-surgery GBM recurrence and eventually prolonging the life expectancy of GBM patients.

Polymeric long-acting drug delivery systems (LADDS) for treatment of chronic diseases: Inserts, patches, wafers, and implants

“…FDM was employed for fabricating various geometry of curcumin-loaded PCL filaments. results suggest the therapeutic potential of drug loaded implants for controlling the recurrence of malignant cancers [198].…”

Role of 3D Printing in the Development of Biodegradable Implants for Central Nervous System Drug Delivery

“…Encapsulating ATRA in PCL prevented the fast degradation of ATRA (t 1/2 = 1 h, in water). 3D-printed biodegradable and flexible scaffolds of curcumin-loaded, polycaprolactone-fused deposition modeling against glioblastomas displayed sustained release of curcumin up to 77 h. 114 The amount released varied with the designs selected with the high cytotoxicity of scaffolds seen against the U87 human glioblastoma cell line. In vivo evaluation, however, was not investigated.…”

“…In vivo evaluation, however, was not investigated. 114 Alginate hydrogel-based mesh loaded with temozolomide microparticles was microextruded on a 3D printer to deliver amphiphilic temozolomide for an extended period at the tumor site. 25 The porous mesh permits higher diffusion of the drug to the external environment due to greater surface-to-volume ratios.…”

Development and Validation of a Novel Tool for Assessing the Environmental Impact of 3D Printing Technologies: A Pharmaceutical Perspective

“…Solvents constitute a major part of some feeds used for 3DP. For instance, in the case of FDM, the components could be melted together [ 62 ] or dissolved in solvent(s) which is then evaporated [ 63 ], and the uniform blend is then extruded into filaments. SSE involves the preparation of feed in a gel form and adjusting it to a suitable viscosity [ 64 ].…”