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Dissolvable Carboxymethylcellulose Microneedles for Noninvasive and Rapid Administration of Diclofenac Sodium
Authors:Ana C Q Silva  Bárbara Pereira  Nicole S Lameirinhas  Paulo C Costa  Isabel F Almeida  Patrícia Dias-Pereira  Inês Correia-Sá  Helena Oliveira  Armando J D Silvestre  Carla Vilela  Carmen S R Freire
Institution:1. CICECO–Aveiro Institute of Materials and Department of Chemistry, University of Aveiro, Aveiro, 3810-193 Portugal;2. UCIBIO–Applied Molecular Biosciences Unit, MedTech–Laboratory of Pharmaceutical Technology & Associate Laboratory i4HB–Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, Porto, 4050-313 Portugal;3. Institute of Biomedical Sciences Abel Salazar, ICBAS-UPorto, University of Porto, Porto, 4050-313 Portugal;4. Department of Plastic, Aesthetic, Reconstructive and Aesthetic Surgery, Centro Hospitalar de S. João, Porto, 4200-319 Portugal;5. Department of Biology & CESAM, University of Aveiro, Aveiro, 3810-193 Portugal
Abstract:The aim of this study is to prepare dissolvable biopolymeric microneedle (MN) patches composed solely of sodium carboxymethylcellulose (CMC), a water-soluble cellulose derivative with good film-forming ability, by micromolding technology for the transdermal delivery of diclofenac sodium salt (DCF). The MNs with ≈456 µm in height displayed adequate morphology, thermal stability up to 200 °C, and the required mechanical strength for skin insertion (>0.15 N needle−1). Experiments in ex vivo abdominal human skin demonstrate the insertion capability of the CMC_DCF MNs up to 401 µm in depth. The dissolution of the patches in saline buffer results in a maximum cumulative release of 98% of diclofenac after 40 min, and insertion in a skin simulant reveals that all MNs completely dissolve within 10 min. Moreover, the MN patches are noncytotoxic toward human keratinocytes. These results suggest that the MN patches produced with CMC are promising biopolymeric systems for the rapid administration of DCF in a minimally invasive manner.
Keywords:carboxymethylcellulose  diclofenac sodium salt  micromolding  microneedles  pain relief  transdermal drug delivery
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