Recent progress of polymeric microneedle-assisted long-acting transdermal drug delivery

Abstract

Microneedle (MN)-assisted drug delivery technology has gained increasing attention over the past two decades. Its advantages of self-management and being minimally invasive could allow this technology to be an alternative to hypodermic needles. MNs can penetrate the stratum corneum and deliver active ingredients to the body through the dermal tissue in a controlled and sustained release. Long-acting polymeric MNs can reduce administration frequency to improve patient compliance and therapeutic outcomes, especially in the management of chronic diseases. In addition, long-acting MNs could avoid gastrointestinal reactions and reduce side effects, which has potential value for clinical application. In this paper, advances in design strategies and applications of long-acting polymeric MNs are reviewed. We also discuss the challenges in scale manufacture and regulations of polymeric MN systems. These two aspects will accelerate the effective clinical translation of MN products.

Keywords: drug delivery systems; long-acting drug release; microneedles; polymeric; transdermal.

FIGURE 1

Application fields of MNs: drug delivery, cosmetic medicine, and medical devices. [9] Copyright 2016, Materials Science and Engineering: R: Reports. [10] Copyright 2023, Biomaterials science. [11] Copyright 2022, Journal of Controlled Release.

FIGURE 2

Four different types of long-acting polymeric MNs. (A) Nano/microparticle-loaded dissolving MNs, (B) Biodegradable polymeric MNs, (C) Swellable polymeric MNs, and (D) Back-layer reservoir polymeric MNs.

FIGURE 3

Design strategies of a rapidly separable degradable polymer MN patch for contraception. (i) Effervescent MN patch: A) Schematic plot. B) Microscope images before and after MN patch was placed in PBS solution. C) Pharmacokinetics in rats [42] copyright 2019, Science Advances. (ii) Porous-backing MN patch: A) Schematic plot. B) Microscopy and scanning electron microscopy images. C) In vitro release curve [45] copyright 2021, Journal of Controlled Release.

FIGURE 4

Three types of long-acting polymeric MNs loaded with insulin. (i) Smart MNs fabricated with a two-layer strategy: A) The equilibria between phenylboronic acid (PBA) derivatives and glucose. B) Fabricating schematic. C) Morphology of MNs before and after being inserted into skin within 3 h. D) In vitro insulin release in response to glucose [82] copyright 2019, American Chemical Society. (ii) Basal-bolus insulin-integrated MN patch: A) Schematic of MNs fabricated by three types of materials or loaded with three types of insulin. B) Microscope images of the integrated MNs. C) Blood glucose levels of diabetic rats after application of integrated MNs [75] copyright 2020, Science Advances. (iii) MNs loaded with insulin powder: A) Fabrication and application schematic. B) Microscope images of a single micro-cavity loaded with drug powder. C) Blood glucose levels [68] copyright 2020, Biomaterials.

FIGURE 5

Two types of long-acting polymeric MNs for vaccine. (i) An implanted silk-PVA composite MN patch: A) Optical image of the MN patch. B) confocal image of this MN patch showing Alexa-647 OVA (red) was restricted in needle-tips. C) Release kinetics of OVA loaded in the composite MN patches or PVA MN patches [81]. copyright 2022, Journal of Controlled Release. (ii) Vaccine MNs containing PLGA controlled-release particles: A) Pedestal patch with sulforhodamine B. B) Confocal image of individual pedestal needle containing microparticles loaded with Ovalbumin-Alexa Fluor 647 (fOVA) conjugate. Scale = 250 μm. C) fOVA-loaded ASE microparticles remain in the skin for several days [97]. copyright 2018, Wiley.