Poly (lactic-co-glycolic acid)-based microneedles for drug delivery across different biological barriers

Abstract

Microneedles (MNs) are micro-sized needles that were originally designed as minimally invasive and painless devices capable of piercing the main skin barrier, the stratum corneum, without stimulating nerve fibers, showing promising prospects as an alternative to other drug administration routes. Poly (lactic-co-glycolic acid) (PLGA) is a biodegradable and biocompatible copolymer with favorable mechanical properties, making it particularly suitable for fabrication of MNs for controlled-release drug delivery. This review provides a comprehensive overview of the design, fabrication, and therapeutic potential of PLGA-based MN systems across a broad range of applications, including transdermal systemic delivery, vaccine delivery and topical skin applications. Due to their exceptional virtues, PLGA MNs are further utilized in nontransdermal applications such as ocular, oral cavity, nasal, and other emerging uses that are presented. Eventually, toxicity and safety profile are discussed, and a concluding section on future perspectives is provided.

Introduction

Microneedles (MNs) are minimally invasive devices composed of an array of short needles, typically less than 1 mm in length (Larrañeta et al., 2016a, Nguyen and Banga, 2025, Prausnitz, 2004). These arrays enable the delivery of drugs through the skin by bypassing the outermost layer, the stratum corneum, which acts as the primary barrier to transdermal drug administration (Aldawood et al., 2021). Due to their short size, MNs cause no bleeding and no pain upon application (Larrañeta et al., 2016a). They have been utilised to deliver a wide range of substances, including small drug molecules, protein/peptides, vaccines and micro/nanoparticles (Avcil and Çelik, 2021, Choo et al., 2023, Larrañeta et al., 2016b, Liu et al., 2021). Additionally, MNs have shown promise in alternative therapeutic applications, such as mucosal and ocular drug delivery (Ferreira et al., 2023, Glover et al., 2023).

Traditionally, MNs are used for rapid drug release, facilitating increased permeation across biological barriers. However, over the past decade, there is been growing interest in using MN arrays for sustained drug release over extended periods (Li et al., 2019a, Li et al., 2022, Mc Crudden et al., 2019, Vora et al., 2023b). This approach is particularly suitable for chronic conditions like HIV or schizophrenia (Li et al., 2025a; Tekko et al., 2022) and can also be employed for long-term delivery of potent agents such as hormones and contraceptives (Li et al., 2022; Li et al., 2019a, Li et al., 2019b). This application is attracting attention not only from academic researchers but also from the pharmaceutical industry. Reflecting this interest, the global market for long-acting drug delivery systems was estimated at $13.7 billion in 2023 and is forecast to grow by more than 10.6 % annually through 2034 (Larrañeta and Domínguez-Robles, 2025).

Several strategies have been explored to achieve sustained drug delivery using MN arrays. One such method involves incorporating long-acting suspensions into MNs (Mc Crudden et al., 2018, Rojekar et al., 2021, Tekko et al., 2022), which has been successfully used to deliver proprietary nanosuspension formulations for HIV treatment. However, this approach is generally limited to drugs with particular properties, such as low water solubility. A more versatile method involves using biodegradable polymers capable of prolonged drug release. Polymers like poly(lactic-co-glycolic acid) (PLGA) are widely employed in this context (Malek-Khatabi et al., 2023). These materials can be integrated into MNs in various forms, either as micron or nanoparticles containing the drug, or as implantable needle tips to function as micro-implants (Dawud and Abu Ammar, 2023, He et al., 2020 Lee et al., 2024a, Li et al., 2019a, Li et al., 2023, Peng et al., 2025 Yang et al., 2024a).

Among the polymers studied for controlled drug release, PLGA stands out as the most commonly used (Malek-Khatabi et al., 2023). Consequently, this review will focus on the integration of MNs with PLGA for the delivery of pharmaceuticals and vaccines. The following sections will introduce PLGA’s characteristics, explore different types of MNs reported in the literature, and present various applications of these systems. The review concludes with a discussion on future prospects in the field.

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Poly(lactic-co-glycolic acid)

This section summarises the basic physicochemical properties of PLGA and how this polymer can be processed. Other review articles have described extensively the properties of this polymer and its applications in drug delivery and tissue engineering (Gentile et al., 2014, Makadia and Siegel, 2011, Omidian and Wilson, 2025, Siepmann and Siepmann, 2025). PLGA is an aliphatic polyester copolymer formed by polylactic acid (PLA) and polyglycolic acid (PGA) units (Fig. 1A) (Maurus and Kaeding, 2004).

Shelly Keisar, Qonita Kurnia Anjani, Abraham M. Abraham, Lalitkumar K. Vora, Eneko Larrañeta, Ryan F. Donnelly, Aiman Abu Ammar, Poly (lactic-co-glycolic acid)-based microneedles for drug delivery across different biological barriers, International Journal of Pharmaceutics, Volume 690, 2026, 126529, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2025.126529.

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