Strategies to develop polymeric microneedles for controlled drug release

The remarkable appeal of microneedle controlled-release systems has captivated both the academic community and pharmaceutical industry due to their great potential for achieving spatiotemporally controlled release, coupled with the minimally invasive nature and ease of application. Over the years, scientists have dedicated their efforts to advancing microneedle systems by manipulating the physicochemical properties of matrix materials, refining microneedle designs, and interfacing with external devices to provide tailored drug release profiles in a spatiotemporally controllable manner. Expanding upon our understanding of drug release mechanisms from polymeric microneedles, which include diffusion, swelling, degradation, triggering, and targeting, there is a growing focus on manipulating the location and rate of drug release through innovative microneedle designs. This burgeoning field of microneedle-based drug delivery systems offers further prospects for precise control over drug release. The design strategies of polymeric microneedle systems for temporally controlled and locally targeted release, as well as the delivery mechanisms by which drugs can be released from a microneedle system are critically reviewed in this work. Furthermore, this review also puts forward some perspectives on the potential and challenges involved in translating these microneedle-based delivery systems into the next generation therapies.

Introduction

Technological innovations in pharmaceutical drug release systems in recent decades have and expect to fundamentally change the field of pharmacotherapy. The development of controlled-release systems provides substantial benefits in numerous diseases treatment by maintaining steady therapeutic concentration for the desired treatment duration while eliminating the need for frequent or specialized drug administration [1]. Research endeavors in this field predominantly aim to develop a diverse range of controlled-release formulations for the treatment of various pathological and clinical disorders. From the view of patient compliance, oral controlled-release formulations have been the emphasis of pharmaceutical research owing to ease of administration and cost-effective manufacturing processes, but the drug release profile is susceptible to the frequently changing gastrointestinal physiology during the practical application [2]. Along these lines, parenteral injections or surgical implants are typically required to provide the desired systemic effect for therapeutic biologics that are susceptible to first-past metabolism [3]. The fundamental disadvantage of these controlled-release devices, however, is that they are associated with painful and invasive medical procedures, which significantly limits their wider applicability. Early efforts to achieve minimally invasive drug delivery involved the use of transdermal controlled-release systems, complexes of drugs with chemical enhancers, or physical methods including iontophoresis and phonophoresis delivery techniques [4], [5], [6], [7], [8]. In recent years, the development and improvement of microneedle-based patches has attracted increased interest in this field since it allows for controlled drug release over time without the discomfort and complexity of current transdermal devices [9], [10], [11], [12].

The microneedle system is built on the integral formation of micron-scale needles onto a patch substrate, which can expand the range of drug molecules and formulations open to dermal delivery through the pain-free mechanical disruption of the skin barriers [13], [14]. For such a barrier-disruption mechanism, effective transport of diverse bioactive materials into the skin by a brief microneedle administration is desirable while avoiding skin injury, neatly integrating the benefits of skin injection and the safety of transdermal patch [15], [16], [17]. Overall, this system provides patients with convenience while also having the potential to bring further pharmacoeconomic benefits. Diligent research endeavors over the last few decades have yielded substantial evidence supporting the versatile potential of the microneedle system, characterized by prominent attributes, across a myriad of biomedical applications including immunobiological administration [18], disease diagnosis [19], cosmetic uses [20], and more typically, delivery of drugs across the skin [21], [22]. Clinical findings, combined with tissue tolerability, patient acceptability, and the ability to self-administer, position the microneedle system as a user-friendly platform for controlled transdermal drug release in a variety of contexts [23], [24].

As per current understanding, the design of a microneedle system with a controllable drug-release pattern is predominantly influenced by the inherent properties of matrix materials, drug-binding affinity, and the interior body environment. In the absence of additional external stimulus, the mechanisms governing controlled drug release in microneedles include generally delayed diffusion, swelling, and degradation controls [25]. Related studies have also explored the synergistic integration of stimuli-responsive materials with microneedle systems, envisioning intelligent and automatic drug delivery in response to specific biological triggers or target sites [26], [27], [28]. Furthermore, encouraged by the triumphs witnessed in transdermal controlled drug delivery through microneedles, several innovative designs have emerged, showcasing the potential to achieve targeted and controlled delivery of therapeutic agents to precise cells, tissues, or sites. This innovative approach holds promise in enhancing treatment efficacy and minimizing system toxicity [29]. In this review, we concentrated on the recent advancements of the microneedle system in terms of controlled drug release and discussed the mechanisms of controlled delivery from microneedles in detail.

Bo Zhi Chen, Yu Ting He, Ze Qiang Zhao, Yun Hao Feng, Ling Liang, Juan Peng, Chen Yu Yang, Hiroshi Uyama, Mohammad-Ali Shahbazi, Xin Dong Guo, Strategies to develop polymeric microneedles for controlled drug release, Advanced Drug Delivery Reviews, Volume 203, 2023, 115109, ISSN 0169-409X,
https://doi.org/10.1016/j.addr.2023.115109.