Translation of Polymeric Microneedles for Treatment of Human Diseases: Recent Trends, Progress, and Challenges

Abstract

The ongoing search for biodegradable and biocompatible microneedles (MNs) that are strong enough to penetrate skin barriers, easy to prepare, and can be translated for clinical use continues. As such, this review paper is focused upon discussing the key points (e.g., choice polymeric MNs) for the translation of MNs from laboratory to clinical practice. The review reveals that polymers are most appropriately used for dissolvable and swellable MNs due to their wide range of tunable properties and that natural polymers are an ideal material choice as they structurally mimic native cellular environments. It has also been concluded that natural and synthetic polymer combinations are useful as polymers usually lack mechanical strength, stability, or other desired properties for the fabrication and insertion of MNs. This review evaluates fabrication methods and materials choice, disease and health conditions, clinical challenges, and the future of MNs in public healthcare services, focusing on literature from the last decade.

Keywords: human disease; polymeric microneedle; transdermal drug delivery; vaccine delivery.

Figure 1

Bar charts displaying the total number of publications on MNs, and the number of MN publications related to polymeric MNs over the 5-year intervals. Information accessed on 26 June 2021 at www.scopus.com.

Figure 2

A schematic diagram for the mechanism of drug delivery: (A) dissolving MNs and (B) swellable MNs. The MN completely dissolve in skin in the case of (A), while there is no polymer dissolution in skin for the case of (B).

Figure 3

Several parameters affecting the design and performance of polymeric MNs.

Figure 4

Illustrating the comparative penetration of hypodermic needle and microneedles (MNs), Reproduced with permission from [113], Elsevier, 2011.

Figure 5

Relationship between sumatriptan released and time by the model (solid line) and in vitro (solid dots) for dissolving MN formulations, reproduced with permission from [32], Elsevier, 2020.

Figure 6

Relationship between the accumulative (A) aspirin and (B) albumin release ratio vs. time for modelling results and experiments, as reported by Chavoshi et al., reproduced with permission from [21], Springer Nature, 2019.

Figure 7

Polymeric MNs manufacturing using micro molding method, reproduced with permission from [150], Elsevier, 2016.

Figure 8

Schematic illustration of dissolving microneedle fabrication via droplet-born air blowing method. (A) Biopolymer dispensing on the flat surface for base structure fabrication. (B) Dispensing of drug-containing droplet over the base structure. (C) Contact of dispensed droplet by downward movement of upperplate. (D) Control of microneedle length. (E) Air blowing-mediated solidification of droplet to shape microneedle structure. (F) Separation of two plates producing dissolving microneedle arrays on upper and lower plates. Droplet-born air blowing (DAB) technology for fabricating polymeric MNs, reproduced with permission from [70], Elsevier, 2013.

Figure 9

Illustration of the process involved in 3D printing of polymeric MNs. Adapted from [162], Springer Nature, 2019.

Figure 10

(A) The growth curves of B16-F10 tumors in mice. The asterisks (*) in (A) indicates that the values of the 5-FU cream group and the MN + 5-FU cream group are different on day 13, 15, and 17 (P < 0.05). (B) Digital photographs of tumors at the end of the study. (C) The weights of tumors at the end of the study. (D) The changes in the body weight of B16-F10 mice, reproduced with permission from [256], Elsevier, 2013.

Figure 11

The amount of 5-FU in an aqueous solution diffused through full-thickness mouse skin treated (●) or not treated (◌) with MNs as a function of time, reproduced with permission from [256], Elsevier, 2013.

Figure 12

Current MN devices. (A) Micro structured Transdermal System, (B) Microinfusor, (C) Macroflux^®, (D) MTS Roller™, (E) Micro-trans™, (F) h-patch™, (G) MicronJet, (H) Intanza^®, reproduced with permission from [326], Elsevier, 2014.

Figure 13

(A) Comparative percentage of completed MN clinical trials on ClinicalTrials.gov database. In total, 76 clinical trials data were found in distinct phases from the database. Information accessed on 21 February 2021 at www.clinicaltrials.gov, and (B) the number of issued US Patents for MN per year from 2000 to 2020. A total of 252 MN patents are available on the database. Information accessed on 21 February 2021 at http://patft.uspto.gov/.

Figure 14

(A) Schematic illustrating the overall configuration used for measuring therapeutic benefits of infarcted heart microsomal cells. This groundbreaking work paves the way for the potential production for organ recovery and reconstruction of cell integrated MNs, reproduced with permission from [400], American Association for the Advancement of Science, 2018. (B) MN patch-assisted PD1 scheme for the prevention of skin cancer. Innovative projects pave the way for the potential creation of cancer immunotherapy focused on MNs, reproduced with permission from [401], American Chemical Society, 2016.