Microneedles in Smart Drug Delivery

Abstract

Significance: In biomedical setup, at large, and drug delivery, in particular, transdermal patches, hypodermal needles, and/or dermatological creams with the topical appliance are among the most widely practiced routes for transdermal drug delivery. Owing to the stratum corneum layer of the skin, traditional drug delivery methods are inefficient, and the effect of the administered therapeutic cues is limited. Recent Advances: The current advancement at the microlevel and nanolevel has revolutionized the drug delivery sector. Particularly, various types of microneedles (MNs) are becoming popular for drug delivery applications because of safety, patient compliance, and smart action. Critical Issues: Herein, we reviewed state-of-the-art MNs as a smart and sophisticated drug delivery approach. Following a brief introduction, the drug delivery mechanism of MNs is discussed. Different types of MNs, that is, solid, hollow, coated, dissolving, and hydrogel forming, are discussed with suitable examples. The latter half of the work is focused on the applied perspective and clinical translation of MNs. Furthermore, a detailed overview of clinical applications and future perspectives is also included in this review. Future Directions: Regardless of ongoing technological and clinical advancement, the focus should be diverted to enhance the efficacy and strength of MNs. Besides, the possible immune response or interference should also be avoided for successful clinical translation of MNs as an efficient drug delivery system.

Keywords: drug delivery system; fabrication strategies; influencing factors; microneedles; microneedles types.

Muhammad Bilal, PhD

Figure 1.

Schematic illustration of drug release from different types of MNs. (1) Stratum corneum, (2) epidermis, and (3) dermis. MNs, microneedles.

Figure 2.

Illustration of various designs of solid MNs with respect to shape and tips. (a) Cylindrical; (b) tapered tip; (c) canonical; (d) square base; (e) pentagonal-base canonical tip; (f) side-open single lumen; (g) double lumen; (h) side-open double lumen. Reprinted from Ashraf et al. with permission under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0). Copyright (2011) the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.

Figure 3.

(a) Shapes of PLA MNs with 600, 700, and 800 μm sizes. (b) Percentage of successful insertion of different sized MNs. (c) The blood glucose level of mice treated with insulin with MN pretreatment without MN. Subcutaneous insulin injection and nontreated. PLA, poly(lactic acid). (d) Relationship between percentage of successful insertions and the number of insertions with MNs with different heights. The microscopic images of porcine skin treated with the MNs at 1^st, 10^th and 20^th insertion are provided on the left, top and right of the graph respectively. Each data point represents the average of 5 experiments. Standard deviation bars are shown. and (e) Blood glucose levels as a percentage of the initial value in mice after subcutaneous hypodermic insertions of insulin (▾), transdermal insulin delivery using MNs (▪), transdermal insulin delivery without MNs pretreatment (•) and time control (▴). Each data point represents the average of 5 experiments. Standard deviation bars are shown. Reprinted from Li et al. with permission under the terms and conditions of a Creative Commons Attribution-Non Commercial 3.0 Unported Licence. An open-access article published by the Royal Society of Chemistry.

Figure 4.

(A) Schematics of the fabrication process of dissolving gelatin/CMC MN patches. The drug was localized in the tip of the needles. (B) Gross view of the gelatin/CMC MN patch. Scale bar = 5 mm. (C) Average dimensions of geometrical parameters of gelatin/CMC MN patches. Reprinted from Chen et al. with permission under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0). Copyright (2018) the authors; Licensee MDPI, Basel, Switzerland.

Figure 5.

(A) Stereomicroscopy images and (B, C) scanning electron microscopy images of gelatin/CMC MNs before insertion. (D–F) The MNs 10 min after insertion. (G–I) The MNs 30 min after insertion. Scale bar = 500 μm. Reprinted from Chen et al. with permission under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0). Copyright (2018) the authors; Licensee MDPI, Basel, Switzerland.

Figure 6.

Potential applications of MNs. Each application strongly depends on the MN type and materials used for fabrication.

Figure 7.

Co-delivery of M2e virus-like particles with influenza split vaccine to the skin using MNs. Reprinted from Kim et al. with permission under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0). Copyright (2019) the authors; Licensee MDPI, Basel, Switzerland.