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Review
. 2021 Jan 6;10(2):181.
doi: 10.3390/jcm10020181.

Microneedle Arrays Combined with Nanomedicine Approaches for Transdermal Delivery of Therapeutics

Vahid Alimardani  1 , Samira Sadat Abolmaali  1   2 , Gholamhossein Yousefi  2 , Zahra Rahiminezhad  1 , Mehdi Abedi  1 , Alimohammad Tamaddon  1   2 , Samad Ahadian  3
Affiliations
Review

Microneedle Arrays Combined with Nanomedicine Approaches for Transdermal Delivery of Therapeutics

Vahid Alimardani et al. J Clin Med. .

Abstract

Organic and inorganic nanoparticles (NPs) have shown promising outcomes in transdermal drug delivery. NPs can not only enhance the skin penetration of small/biomacromolecule therapeutic agents but can also impart control over drug release or target impaired tissue. Thanks to their unique optical, photothermal, and superparamagnetic features, NPs have been also utilized for the treatment of skin disorders, imaging, and biosensing applications. Despite the widespread transdermal applications of NPs, their delivery across the stratum corneum, which is the main skin barrier, has remained challenging. Microneedle array (MN) technology has recently revealed promising outcomes in the delivery of various formulations, especially NPs to deliver both hydrophilic and hydrophobic therapeutic agents. The present work reviews the advancements in the application of MNs and NPs for an effective transdermal delivery of a wide range of therapeutics in cancer chemotherapy and immunotherapy, photothermal and photodynamic therapy, peptide/protein vaccination, and the gene therapy of various diseases. In addition, this paper provides an overall insight on MNs' challenges and summarizes the recent achievements in clinical trials with future outlooks on the transdermal delivery of a wide range of nanomedicines.

Keywords: drug delivery; gene delivery; immunotherapy; microneedle arrays; nanomedicine; vaccination.

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Conflict of interest statement

The authors declare that they have no conflict of interests.

Figures

Figure 1
Figure 1
Vesicular, lipid and polymer-based nanoparticles (NPs) currently used in nanomedicine and their underlying mechanisms for enhanced transdermal delivery (TDD).
Figure 2
Figure 2
A schematic representation of delivery approaches using various types of microneedle arrays (MNs): (A) poke-and-patch (solid MNs), (B) coat-and-poke (coated MNs), (C) poke-and-flow (hollow MNs), (D) poke-and-dissolve (dissolvable MNs), and (E) poke-and-release (hydrogel forming MNs).
Figure 3
Figure 3
Combinatorial applications of microneedles (MNs) with nanoparticles (NPs).
Figure 4
Figure 4
Schematic preparation of the aPD1 containing hyaluronic acid microneedles (HA MNs) for the prevention of skin cancer: (a) MNs containing the pH-sensitive dextran nanoparticles encapsulating catalase/glucose oxidase (CAT/GOx) enzyme system that convert the blood glucose to gluconic acid and leading to aPD1 sustained release; (b) aPD1 released from the MNs blocks the PD-1 receptor, which resulted in activating the immune cells to kill skin cancer cells; CAT and GOx stand for the catalase and glucose oxidase, respectively. Reprinted with permission from [45].
Figure 5
Figure 5
Graphical presentation of the mechanism for the antitumor effect of microneedles in combination with indocyanine green-loaded chitosan NPs (ICG-NPs).
Figure 6
Figure 6
(a) PcNP@Drug synthesis and its skin penetration. Phthalocyanine was modified with four silicate units (Pc-Si), Pc units excited by far-red light and acting as photosensitizers, then the Pc-conjugated mesoporous organosilica nanoparticle (PcNP) was fabricated via silane co-condensation and hydrolysis using Pc-Si. In this process, hexadecyltrimethylammonium bromide (CTAB) acts as the structure-directing agent, triethanolamine (TEOA) acts as a basic catalyst and tetramethyl orthosilicate (TMOS) acts as the inorganic silica agent. To prepare PcNP@Drug, dabrafenib and trametinib, as small inhibitor drugs, were encapsulated into the PcNP pores. PcNP@Drug was then delivered to mice skin through a microneedle patch. (b) PcNP@Drug cellular uptake: under NIR light irradiation, PcNP@Drug produced reactive oxygen species (ROS) in-vivo and the drugs’ release of PcNP@Drug destroyed cancer cells. Reprinted with permission from [146].
Figure 7
Figure 7
Schematic presentation of the ZnO quantum dots QDs which capped the pores of mesoporous bioactive glass NPs (MBGNs) integrated with PVP MNs for the glucose mediated TDD of insulin. After penetration into the skin and participation in the body circulation, GOx and CAT in the MBGs convert glucose to gluconic acid, resulting in decreasing the local pH and dis-assembly of ZnO QD caps, leading to the opening of MBGs’ nanopores and then releasing the insulin molecules. Reprinted with permission from [109].
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