Here, we present a new hybrid additive manufacturing (AM) process to create drug delivery systems (DDSs) with selectively incorporated drug depots. The matrix of a DDS was generated by stereolithography (SLA), whereas the drug depots were loaded using inkjet printing. The novel AM process combining SLA with inkjet printing was successfully implemented in an existing SLA test setup. In the first studies, poly(ethylene glycol) diacrylate-based specimens with integrated depots were generated. As test liquids, blue and pink ink solutions were used. Furthermore, bovine serum albumin labeled with Coomassie blue dye as a model drug was successfully placed in a depot inside a DDS. The new hybrid AM process makes it possible to place several drugs independently of each other within the matrix. This allows adjustment of the release profiles of the drugs depending on the size as well as the position of the depots in the DDS.
Novel fabrication techniques based on photopolymerization enable the preparation of complex multi-material constructs for biomedical applications. This requires an understanding of the influence of the used reaction components on the properties of the generated copolymers. The identification of fundamental characteristics of these copolymers is necessary to evaluate their potential for biomaterial applications. Additionally, knowledge of the properties of the starting materials enables subsequent tailoring of the biomaterials to meet individual implantation needs. In our study, we have analyzed the biological, chemical, mechanical and thermal properties of photopolymerized poly(ethyleneglycol) diacrylate (PEGDA) and specific copolymers with different photoinitiator (PI) concentrations before and after applying a post treatment washing process. As comonomers, 1,3-butanediol diacrylate, pentaerythritol triacrylate and pentaerythritol tetraacrylate were used. The in vitro studies confirm the biocompatibility of all investigated copolymers. Uniaxial tensile tests show significantly lower tensile strength (82% decrease) and elongation at break (76% decrease) values for washed samples. Altered tensile strength is also observed for different PI concentrations: on average, 6.2 MPa for 1.25% PI and 3.1 MPa for 0.5% PI. The addition of comonomers lowers elongation at break on average by 45%. Moreover, our observations show glass transition temperatures (Tg) ranging from 27 °C to 56 °C, which significantly increase with higher comonomer content. These results confirm the ability to generate biocompatible PEGDA copolymers with specific thermal and mechanical properties. These can be considered as resins for various additive manufacturing-based applications to obtain personalized medical devices, such as drug delivery systems (DDS). Therefore, our study has advanced the understanding of PEGDA multi-materials and will contribute to the future development of tools ensuring safe and effective individual therapy for patients.
Current research activities focus on personalized, comfortable and safe products for systemic or local drug application in patients. Poly(ethylene glycol) diacrylate is in particular interest as a drug delivery material, as it shows appropriate biological properties such as hydrophilicity and low toxicity. Additionally, as an easily photopolymerizable compound it can be also utilized for the production of scaffolds with the use of different techniques such as stereolithography. Even though it is often used as a biomaterial or as a copolymer in many photopolymer systems for drug delivery, thermomechanical analysis and basic understanding are rare.Therefore, we investigated the tensile stress and the glass transition temperature of pure PEGDA and of its copolymers with 1,3-butanediol diacrylate or pentaerythritol triacrylate, as a function of the photoinitiator (PI) or acrylate concentration. Additionally, we demonstrated that the washing procedure decreases the tensile stress values. We showed, that by the means of composing PEGDA with these, it is possible to influence thermomechanical properties of the sample. Our outcomes have revealed, that there is no clear influence of the PI concentration on the thermomechanical properties. However there is an influence of the monomer concentration. Therefore, it should be possible to modify drug release profiles in future experiments.
Individually tailored drug delivery systems (DDSs) are considered one of the most promising therapeutic tools for the creation of safe and effective treatments. DDSs as a novel approach should be beneficial in curing systemic as well as local ailments, where a high topical concentration of the drug and a reduction of side effects are desirable. It could also be favorable for patients requiring customized treatments, showing atypical profiles of drug metabolism. Development of particular drug delivery devices require the selection of a suitable scaffold material, which should exhibit proper mechanical and biological properties, but also enable adjustment of the drug release according to a specific need. Thus, it is extremely important to expand the knowledge concerning potential DDS components. Poly(ethylene glycol) diacrylate (PEGDA) according to its properties can be easily used as a DDS resin and shaped into a desired structure with the employment of techniques based on photopolymerization, including some novel 3D printing techniques. As a continuation of our previous works, in this paper drug release studies from conventionally prepared PEGDA scaffolds are presented. We have shown that in PEGDA materials, the release profile of the low molecular weight model drug acetylsalicylic acid can be altered by water content. PEGDA as a delivery material should be further investigated to specify its potential as a comonomer and a matrix for pharmaceutical agents.
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