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Analysis of In Vitro Cytotoxicity of Carbohydrate-Based Materials Used for Dissolvable Microneedle Arrays

Authors
  • Yalcintas, Ezgi P.1
  • Ackerman, Daniel S.1, 1
  • Korkmaz, Emrullah1
  • Telmer, Cheryl A.1
  • Jarvik, Jonathan W.1, 1
  • Campbell, Phil G.1, 1
  • Bruchez, Marcel P.1, 1, 1
  • Ozdoganlar, O. Burak1, 1, 1
  • 1 Carnegie Mellon University, Pittsburgh, Pennsylvania, 15213, USA , Pittsburgh (United States)
Type
Published Article
Journal
Pharmaceutical Research
Publisher
Springer-Verlag
Publication Date
Jan 15, 2020
Volume
37
Issue
3
Identifiers
DOI: 10.1007/s11095-019-2748-7
Source
Springer Nature
Keywords
License
Yellow

Abstract

PurposeDissolvable 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).MethodsEach 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.ResultsQualitative 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.ConclusionsIt 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.

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