Enhancing transdermal drug delivery with dissolving microneedles: A review of optimization strategies and challenges

Abstract

Microneedles represent a novel transdermal drug delivery technology that relies on micron-sized needle structures. This approach effectively penetrates the stratum corneum to achieve localized or systemic therapeutic effects, addressing the pain associated with traditional injections and the low bioavailability issues of oral administration. It addresses the pain associated with traditional injections and the low bioavailability of oral administration. Dissolving microneedles have emerged as a research hotspot in microneedle technology due to their distinctive advantages, including dissolvability, ease of operation, and absence of sharp waste. They have garnered widespread attention and application in the pharmaceutical field as an efficient means to enhance transdermal drug absorption. However, many drugs (particularly poorly soluble ones) require higher transdermal absorption enhancement factors, which traditional dissolving microneedles struggle to meet. In light of this, this paper will compare dissolving microneedles with other types of microneedles, propose optimization strategies for dissolving microneedle technology, discuss existing challenges, and outline future research directions, aiming to provide valuable references for the further development of dissolving microneedles.

Introduction

Transdermal drug delivery systems refer to a technological framework that administers drugs through the skin, employing methodologies from pharmaceutics, physics, chemistry, and other disciplines to facilitate drug penetration across the skin surface into systemic circulation, thereby achieving localized or systemic therapeutic effects.1 This technology has garnered widespread attention due to its advantages in bypassing hepatic first-pass metabolism and improving patient compliance.2 However, the barrier function of the skin, particularly the stratum corneum, limits the transdermal absorption efficiency of most drugs.3 As the largest organ of Homo sapiens, the stratum corneum exhibits a unique “brick-and-mortar” microstructure of Broussonetia papyrifera,4 forming a relatively dense and continuous barrier at the outermost layer of the skin. This barrier effectively prevents water loss while protecting against external physical, chemical, and biological insults, thereby maintaining skin health and normal function.5 Such barrier properties restrict the transdermal absorption efficiency of most topical formulations (e.g., ointments, patches, emulsions, etc.), necessitating the development of efficient TDDS to overcome this challenge.

The emergence of microneedle technology offers an innovative solution to this problem. Microneedles are needle-like structures fabricated via microfabrication techniques, with tip diameters typically ranging from tens of micrometers and lengths spanning from tens of micrometers to several millimeters, which can be configured as single needles or multi-needle arrays.6 Owing to their good skin-penetrating capability, microneedles demonstrate minimally invasive, convenient, and precise characteristics, enabling their widespread application across multiple fields, as shown in Fig. 1. Specifically, they exhibit strong potential in drug delivery (encompassing traditional Chinese medicine,7 chemical drugs,8 and biologics9), clinical diagnostics (including interstitial fluid extraction,10 blood glucose monitoring,11 and tumor screening12), medical aesthetics (e.g., alopecia treatment,13 facial acne management,14 and pigmentation improvement15), as well as interdisciplinary research16 (involving engineering, physics, chemistry, pharmacology, etc.).

Dissolving microneedle technology, as a successful approach for promoting transdermal drug absorption, has achieved some accomplishments in the pharmaceutical field that have captured the attention of Homo sapiens. It has overcome numerous limitations of traditional transdermal drug delivery,17 providing an innovative pathway for drugs to efficiently penetrate deep into the skin, enhancing transdermal absorption efficiency, transforming the administration methods of many drugs, and improving both patient medication experience and therapeutic outcomes. However, it is undeniable that many drugs, particularly those with poor solubility, impose higher demands on transdermal absorption efficiency. Due to their inherent physicochemical properties, these poorly soluble drugs face multiple barriers during skin penetration.18 Although conventional dissolving microneedle technology has demonstrated excellent performance, it still struggles to meet the stringent requirements for transdermal absorption efficiency, failing to achieve the desired therapeutic dosage and efficacy.

Therefore, how to further improve the transdermal absorption-enhancing effects of dissolving microneedles has become a focal point of current research in the pharmaceutical field. This not only concerns the full realization of the therapeutic potential of poorly soluble drugs but also determines whether more effective treatment options can be provided to a broader patient population. Based on this, we have conducted a comprehensive review in this field. By comparing the characteristics of dissolving microneedles with other types of microneedles, we systematically summarize the common preparation techniques for dissolving microneedles, propose design optimization strategies, and discuss potential challenges and corresponding solutions associated with this technology. Our aim is to provide valuable insights for the future development and application of dissolving microneedles.

Solid microneedles

Solid microneedles are typically fabricated from silicon,19 ceramics,20 glass,21 metals (such as stainless steel).22 Their primary mechanism involves piercing the skin to create microchannels, thereby enhancing skin permeability for subsequent drug or bioactive substance delivery.23 For instance, silicon microneedles exhibit excellent mechanical properties and precise manufacturing processes, enabling the production of highly uniform microneedle arrays. Metal microneedles, on the other hand, possess superior conductivity, making them suitable for electro-assisted drug delivery or biosensing applications.24 However, since solid microneedles are primarily composed of metals and non-degradable components, needle breakage or damage during administration may result in retention within the skin, posing safety risks to patients. Additionally, the dynamic recovery of microchannels created by solid microneedles can lead to inaccurate dosing.25

Hollow microneedles

Hollow microneedles resemble miniature syringe needles, featuring internal channels for direct drug injection. Their working principle involves inserting the microneedles into the skin and delivering drugs through the hollow channels under pressure.26 Materials used for fabrication include polylactic acid,27 silicon,28 metals, and silica.29 Compared to conventional syringes, hollow microneedles can reduce pain and tissue damage during injection. For example, in insulin administration, hollow microneedles offer a more convenient and comfortable option for diabetic patients.30 It should be noted that the fabrication of hollow microneedles is a complex process requiring rigorous manufacturing techniques to create hollow structures. Additionally, the presence of drug residues or skin fragments may obstruct the hollow channels, thereby impeding or compromising the effective delivery of drugs.31

Coated microneedles

Coated microneedles are solid microneedles coated with drugs or bioactive substances, using similar materials as solid microneedles. Upon skin penetration, the coated substances are released. The principle involves coating water-soluble drug formulations onto the microneedle surface to form a drug film. After insertion, the drug dissolves and diffuses into the skin, followed by microneedle removal to complete drug release.32 Materials include titanium,33 silicon,34 ceramics,35 stainless steel, and polylactic acid.36 While coated microneedles simplify drug delivery, their limited surface area restricts drug-loading capacity.37

Dissolving microneedles

Dissolving microneedles are fabricated using biodegradable, water-soluble polymers or polysaccharides as matrix materials to encapsulate drugs. Common materials include hyaluronic acid (HA),38 chitosan,39 polyvinylpyrrolidone (PVP),40 polyvinyl alcohol (PVA),41 gelatin (GEL), and starch.42 Upon insertion, the microneedle matrix dissolves upon contact with interstitial fluid, releasing the drug locally. Dissolving microneedles address issues like needle breakage and retention associated with silicon or glass microneedles while improving drug-loading capacity and expanding applications. By selecting different materials and needle geometries, rapid-release, controlled-release, or sustained-release dissolving microneedles can be designed.43 However, due to the unique properties of the preparation materials, the mechanical strength of dissolving microneedles is insufficient, which may lead to bending of the needle body and consequently affect the efficiency of drug delivery.44

Hydrogel microneedles

Hydrogel microneedles are fabricated from hydrogel polymer matrices, similar to dissolving microneedles. Materials include hyaluronic acid-methacrylate copolymer (HA-MA),45 poly(acrylic acid-co-maleic acid) (PAMA), and PVA.46 Upon insertion, the microneedle array rapidly absorbs interstitial fluid, causing the hydrogel to swell and create continuous drug-release channels. Drugs permeate and diffuse into the skin through these channels. Hydrogel microneedles resist pore closure and can be fully retrieved after insertion. Moreover, drug release rates can be modulated by adjusting the crosslinking density of hydrogel fibers. However, hydrogel swelling may cause skin irritation or redness.47

Bioresponsive microneedles

Bioresponsive microneedles are systems designed to respond to pathological signals (e.g., pH, glucose concentration, enzyme activity) or external stimuli (e.g., light, heat, electricity, magnetism) in vivo. Their design leverages stimuli-responsive polymers or materials to activate under specific conditions, enabling precise drug release, biomarker detection, or tissue microenvironment modulation.48 For example, glucose-responsive microneedles can autonomously regulate insulin release based on blood glucose levels, improving the quality of life for insulin-dependent diabetic patients.48

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Zixuan Zhanga, Yongbing Suna, Haocheng Lia, Jianfang Feng, Meng Cheng, Enhancing transdermal drug delivery with dissolving microneedles: A review of optimization strategies and challenges, Journal of Pharmaceutical Sciences, 2026; 115, Volume 115, Issue 7104189July 2026