Biodegradable β-Cyclodextrin Conjugated Gelatin Methacryloyl Microneedle for Delivery of Water-Insoluble Drug

Xingwu Zhou; Zhimin Luo; Avijit Baidya; Han-Jun Kim; Canran Wang; Xing Jiang; Moyuan Qu; Jixiang Zhu; Li Ren; Fereshteh Vajhadin; Peyton Tebon; Niyuan Zhang; Yumeng Xue; Yudi Feng; Chengbin Xue; Yi Chen; KangJu Lee; Junmin Lee; Shiming Zhang; Chun Xu; Nureddin Ashammakhi; Samad Ahadian; Mehmet Remzi Dokmeci; Zhen Gu; Wujin Sun; Ali Khademhosseini

doi:10.1002/adhm.202000527

Biodegradable β-Cyclodextrin Conjugated Gelatin Methacryloyl Microneedle for Delivery of Water-Insoluble Drug

Adv Healthc Mater. 2020 Jun;9(11):e2000527. doi: 10.1002/adhm.202000527. Epub 2020 May 4.

Authors

Xingwu Zhou^{1

2

3}, Zhimin Luo^{1

2

4}, Avijit Baidya^{1

2}, Han-Jun Kim^{1

2}, Canran Wang^{1

2}, Xing Jiang^{1

2

5}, Moyuan Qu^{1

2

6}, Jixiang Zhu^{1

2

7}, Li Ren^{1

2}, Fereshteh Vajhadin^{1

2

8}, Peyton Tebon^{1

2}, Niyuan Zhang^{1

2}, Yumeng Xue^{1

2}, Yudi Feng^{1

2}, Chengbin Xue^{1

2}, Yi Chen^{1

2}, KangJu Lee^{1

2}, Junmin Lee^{1

2}, Shiming Zhang^{1

2}, Chun Xu^{1

2

9}, Nureddin Ashammakhi^{1

2

10}, Samad Ahadian^{1

2

10

11}, Mehmet Remzi Dokmeci^{1

2

10

11}, Zhen Gu^{1

2

12}, Wujin Sun^{1

2}, Ali Khademhosseini^{1

2

3

10

11

12}

Affiliations

¹ Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
² Center for Minimally Invasive Therapeutics, California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
³ Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
⁴ School of Pharmacy, Xi'an Jiaotong University, Xi'an, 710061, China.
⁵ School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
⁶ State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
⁷ Department of Biomedical Engineering, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
⁸ Department of Chemistry, Yazd University, Yazd, 89195, Iran.
⁹ School of Dentistry, The University of Queensland, Herston, QLD, 4006, Australia.
¹⁰ Department of Radiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
¹¹ Terasaki Institute for Biomedical Innovation, Los Angeles, CA, 90064, USA.
¹² Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, 90095, USA.

Abstract

Transdermal delivery of water-insoluble drugs via hydrogel-based microneedle (MN) arrays is crucial for improving their therapeutic efficacies. However, direct loading of water-insoluble drug into hydrophilic matrices remains challenging. Here, a biodegradable MN array patch that is fabricated from naturally derived polymer conjugates of gelatin methacryloyl and β-cyclodextrin (GelMA-β-CD) is reported. When curcumin, an unstable and water-insoluble anticancer drug, is loaded as a model drug, its stability and solubility are improved due to the formation of an inclusion complex. The polymer-drug complex GelMA-β-CD/CUR can be formulated into MN arrays with sufficient mechanical strength for skin penetration and tunable drug release profile. Anticancer efficacy of released curcumin is observed in three-dimensional B16F10 melanoma models. The GelMA-β-CD/CUR MN exhibits relatively higher therapeutic efficacy through more localized and deeper penetrated manner compared with a control nontransdermal patch. In vivo studies also verify biocompatibility and degradability of the GelMA-β-CD MN arrays patch.

Keywords: gelatin methacryloyl; microneedles; transdermal delivery; water insoluble drugs; β-cyclodextrin.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Administration, Cutaneous
Drug Delivery Systems
Gelatin*
Needles
Water
beta-Cyclodextrins*

Substances

beta-Cyclodextrins
Water
Gelatin

Abstract

Publication types

MeSH terms

Substances

Grants and funding