Development and characterization of 3D printed ethylene vinyl acetate (EVA) as drug delivery device for the treatment of overactive bladder

Abstract

The overactive bladder is a condition characterized by a sudden urge to urinate, even with small volumes of urine present in the bladder. The current treatments available for this pathology consist on conservative approaches and the continuous administration of drugs, which when made by conventional methods has limitations related to the first pass metabolism, bioavailability, severe side effects, and low patient adherence to treatments, ultimately leading to low effectiveness. Within this context, the present work proposes the design, manufacture, and characterization of an intravesical implant for the treatment of overactive bladder pathology, using EVA copolymer as a matrix and oxybutynin as a drug. The fabrication of devices through two manufacturing techniques (extrusion and additive manufacturing by fused filament fabrication, FFF) and the evaluation of the implants through characterization tests was proposed. The usability and functionality were evaluated through simulated insertion of the device/prototype in a bladder model through catheter insertion tests. The safety and effectiveness of the devices was investigated from mechanical testing as well as drug release assays. Drug release assays presented a burst release in the first 24 h, followed by a release of 1.8 and 2.8 mg/d, totalizing 32 d. Mechanical tests demonstrated an increase in the stiffness of the specimens due to the addition of the drug, showing a change in maximum stress and strain at break. The released dose was higher than that usually presented when considering the oral administration route, showing the optimization of the development of this implant has the potential to improve the quality of life of patients with overactive bladder.

Keywords:

• Polymers
• ethylene vinyl acetate
• high density polyethylene
• oxybutynin
• overactive bladder
• drug delivery

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article.

CRediT author statement

Study design: Gustavo Ferrari, Loise S. Silva, Renata Cerruti, Carlos Rodrigo de Mello Roesler, Gean Vitor Salmoria, Izabelle de Mello Gindri.

Study development: Gustavo Ferrari, Loise S. Silva, Renata Cerruti.

Data Analysis: Gustavo Ferrari, Loise S. Silva, Renata Cerruti.

Manuscript drafting: Gustavo Ferrari, Loise S. Silva, Renata Cerruti.

Manuscript critical revision: Carlos Rodrigo de Mello Roesler, Gean Vitor Salmoria, Izabelle de Mello Gindri.

Additional information

Funding

Izabelle de Mello Gindri is supported with scholarship by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Gustavo Ferrari is supported with scholarship by the Conselho Nacional de Desenvolvimento Científico e Tecnológico – Brasil (CNPq) – Grant Number 160162/2019-0; Loise Silva is supported with scholarship by the Conselho Nacional de Desenvolvimento Científico e Tecnológico – Brasil (CNPq) – Grant Number 350124/2021-3; Renata Cerruti is supported with scholarship by the Conselho Nacional de Desenvolvimento Científico e Tecnológico – Brasil (CNPq) – Grant Number 350404/2021-6. Professor Gean Vitor Salmoria is supported with scholarship by the Conselho Nacional de Desenvolvimento Científico e Tecnológico – Brasil (CNPq); Professor Carlos Rodrigo de Mello Roesler is supported with scholarship by the Conselho Nacional de Desenvolvimento Científico e Tecnológico – Brasil (CNPq). This study was financed in part by the Conselho Nacional de Desenvolvimento Científico e Tecnológico – Brasil (CNPq).