Microneedle-mediated drug delivery for cutaneous diseases

Abstract

Microneedles have garnered significant interest as transdermal drug delivery route owing to the advantages of nonselective loading capacity, minimal invasiveness, simple operation, and good biocompatibility. A number of therapeutics can be loaded into microneedles, including hydrophilic and hydrophobic small molecular drugs, and macromolecular drugs (proteins, mRNA, peptides, vaccines) for treatment of miscellaneous diseases. Microneedles feature with special benefits for cutaneous diseases owing to the direct transdermal delivery of therapeutics to the skin. This review mainly introduces microneedles fabricated with different technologies and transdermal delivery of various therapeutics for cutaneous diseases, such as psoriasis, atopic dermatitis, skin and soft tissue infection, superficial tumors, axillary hyperhidrosis, and plantar warts.

Keywords: cutaneous disease; drug delivery; microneedle; microneedle fabrication; transdermal route.

FIGURE 1

Number of publications on microneedle based on PubMed database (https://www.ncbi.nlm.nih.gov/pubmed/) and Web of Science (http://apps.webofknowledge.com) on 12 November 2021.

FIGURE 2

Types of microneedles. (A) Solid microneedles. Reproduced with permission (Henry et al., 1998). Copyright 1998, Elsevier. (B) Hollow microneedles. Reproduced with permission (Martanto et al., 2006). Copyright 2006, Springer Nature. (C) Dissolving microneedles. Reproduced with permission (Lee et al., 2008). Copyright 2008, Elsevier. (D) Coated microneedles. Copyright 2007, Springer Nature.

FIGURE 3

The relationship between needle and skin at different stages of insertion: (A) pre-puncture, (B) puncture, and (C) post-puncture. The microneedles are applied to the skin (D), and then used for drug delivery (E). Copyright 2017, Elsevier.

FIGURE 4

(A) Preparation of MTX-loaded dissoluble microneedles. Comparison of orally administered MTX and MTX loaded microneedles with transdermal administration on (B) left ear lesions, (C) H&E staining and (D) Ki67 IHC staining of skin sections (red arrows). Copyright 2019, American Chemical Society.

FIGURE 5

(A) Preparation of soluble high-molecule-wight poly-γ-PGA microneedles. (B) Poly-γ-PGA microneedles performing therapeutic effect within 4 h after transdermal administration. (C) Poly-γ-PGA microneedles could be retained in the skin for 6 days for sustained therapeutic effect. Copyright 2020, Elsevier.

FIGURE 6

(A) Manufacturing process of VAN-loaded microneedle arrays. Application of MN arrays at same CFU counts (B) or same infection length (C). Copyright 2021, John Wiley and Sons.

FIGURE 7

(A) Schematic diagram of a cross-section of warts. (B) Insertion of the bleomycin-coated microneedle. (C) Transdermal delivery of bleomycin into warts. Copyright 2017, Springer Nature.

FIGURE 8

(A) Schematic illustration of co-loaded photosensitizers and small-molecule inhibitors into microneedles for synergistic therapy of deep-seated melanoma. (B) Antitumor effects for these transdermally delivered drugs. Copyright 2018, American Chemical Society.

FIGURE 9

Preparation of granulocyte-macrophage colony-stimulating factor (GM-CSF) loaded microneedles and immune response after transdermal delivery performed using GM-CSF-loaded microneedles. Copyright 2018, Elsevier.