Ezgi P Yalcintas1, Daniel S Ackerman2,3, Emrullah Korkmaz1, Cheryl A Telmer3, Jonathan W Jarvik2,3, Phil G Campbell3,4, Marcel P Bruchez2,3,5, O Burak Ozdoganlar6,7,8. 1. Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, 15213, USA. 2. Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, 15213, USA. 3. Molecular Biosensor and Imaging Center, Carnegie Mellon University, Pittsburgh, Pennsylvania, 15213, USA. 4. Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, 15213, USA. 5. Department of Chemistry, Carnegie Mellon University, Pittsburgh, Pennsylvania, 15213, USA. 6. Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, 15213, USA. ozdoganlar@cmu.edu. 7. Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, 15213, USA. ozdoganlar@cmu.edu. 8. Department of Materials Science and Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, 15213, USA. ozdoganlar@cmu.edu.
Abstract
PURPOSE: Dissolvable microneedle arrays (MNAs) can be used to realize enhanced transdermal and intradermal drug delivery. Dissolvable MNAs are fabricated from biocompatible and water-soluble base polymers, and the biocargo to be delivered is integrated with the base polymer when forming the MNAs. The base polymer is selected to provide mechanical strength, desired dissolution characteristics, and compatibility with the biocargo. However, to satisfy regulatory requirements and be utilized in clinical applications, cytotoxicity of the base polymers should also be thoroughly characterized. This study systematically investigated the cytotoxicity of several important carbohydrate-based base polymers used for production of MNAs, including carboxymethyl cellulose (CMC), maltodextrin (MD), trehalose (Treh), glucose (Gluc), and hyaluronic acid (HA). METHODS: Each material was evaluated using in vitro cell-culture methods on relevant mouse and human cells, including MPEK-BL6 mouse keratinocytes, NIH-3T3 mouse fibroblasts, HaCaT human keratinocytes, and NHDF human fibroblasts. A common laboratory cell line, human embryonic kidney cells HEK-293, was also used to allow comparisons to various cytotoxicity studies in the literature. Dissolvable MNA materials were evaluated at concentrations ranging from 3 mg/mL to 80 mg/mL. RESULTS: Qualitative and quantitative analyses of cytotoxicity were performed using optical microscopy, confocal fluorescence microscopy, and flow cytometry-based assays for cell morphology, viability, necrosis and apoptosis. Results from different methods consistently demonstrated negligible in vitro cytotoxicity of carboxymethyl cellulose, maltodextrin, trehalose and hyaluronic acid. Glucose was observed to be toxic to cells at concentrations higher than 50 mg/mL. CONCLUSIONS: It is concluded that CMC, MD, Treh, HA, and glucose (at low concentrations) do not pose challenges in terms of cytotoxicity, and thus, are good candidates as MNA materials for creating clinically-relevant and well-tolerated biodissolvable MNAs.
PURPOSE: Dissolvable microneedle arrays (MNAs) can be used to realize enhanced transdermal and intradermal drug delivery. Dissolvable MNAs are fabricated from biocompatible and water-soluble base polymers, and the biocargo to be delivered is integrated with the base polymer when forming the MNAs. The base polymer is selected to provide mechanical strength, desired dissolution characteristics, and compatibility with the biocargo. However, to satisfy regulatory requirements and be utilized in clinical applications, cytotoxicity of the base polymers should also be thoroughly characterized. This study systematically investigated the cytotoxicity of several important carbohydrate-based base polymers used for production of MNAs, including carboxymethyl cellulose (CMC), maltodextrin (MD), trehalose (Treh), glucose (Gluc), and hyaluronic acid (HA). METHODS: Each material was evaluated using in vitro cell-culture methods on relevant mouse and human cells, including MPEK-BL6 mouse keratinocytes, NIH-3T3mouse fibroblasts, HaCaT human keratinocytes, and NHDF human fibroblasts. A common laboratory cell line, humanembryonic kidney cells HEK-293, was also used to allow comparisons to various cytotoxicity studies in the literature. Dissolvable MNA materials were evaluated at concentrations ranging from 3 mg/mL to 80 mg/mL. RESULTS: Qualitative and quantitative analyses of cytotoxicity were performed using optical microscopy, confocal fluorescence microscopy, and flow cytometry-based assays for cell morphology, viability, necrosis and apoptosis. Results from different methods consistently demonstrated negligible in vitro cytotoxicity of carboxymethyl cellulose, maltodextrin, trehalose and hyaluronic acid. Glucose was observed to be toxic to cells at concentrations higher than 50 mg/mL. CONCLUSIONS: It is concluded that CMC, MD, Treh, HA, and glucose (at low concentrations) do not pose challenges in terms of cytotoxicity, and thus, are good candidates as MNA materials for creating clinically-relevant and well-tolerated biodissolvable MNAs.
Authors: Emrullah Korkmaz; Emily E Friedrich; Mohamed H Ramadan; Geza Erdos; Alicia R Mathers; O Burak Ozdoganlar; Newell R Washburn; Louis D Falo Journal: Acta Biomater Date: 2015-06-18 Impact factor: 8.947
Authors: Fouad Damiri; Nagavendra Kommineni; Samuel Ogbeide Ebhodaghe; Raviteja Bulusu; Vaskuri G S Sainaga Jyothi; Amany A Sayed; Aeshah A Awaji; Mousa O Germoush; Hamdan S Al-Malky; Mohammed Z Nasrullah; Md Habibur Rahman; Mohamed M Abdel-Daim; Mohammed Berrada Journal: Pharmaceuticals (Basel) Date: 2022-02-03
Authors: Stephen C Balmert; Zohreh Gholizadeh Ghozloujeh; Cara Donahue Carey; Li'an H Williams; Jiying Zhang; Preeti Shahi; Maher Amer; Tina L Sumpter; Geza Erdos; Emrullah Korkmaz; Louis D Falo Journal: iScience Date: 2022-08-30