The introduction of antibiotic therapy reformed modern medicine radically; however, conventional antibiotic delivery, such as oral, parenteral, and topical, poses considerable challenges [1]. Orally administered antibiotics are efficacious; however, demonstrate poor bioavailability, resulting in poor absorption in the bloodstream [2]. These antibiotics undergo first-pass metabolism in the liver, resulting in sub-therapeutic effectiveness. Moreover, oral intake can overexpose gut microbiota to antibiotics, resulting in gut dysbiosis, gastrointestinal side effects, and antimicrobial resistance (AMR) development [2, 3, 4]. Therefore, antibiotics with lower oral bioavailability are administered via the parenteral route, which is invasive and painful, especially for individuals with needle phobia [5]. The parenteral route is associated with systemic toxicity, displays limited suitability for self-administration, and is less patient-compliant [6,7]. Further, the topical route is considered for skin-related infections, however, the inability of larger molecular-weight (MW) antibiotics to penetrate the skin barrier and loss through perspiration, etc., limits their therapeutic efficacy [8]. Additionally, conventional antibiotics encounter the challenge of penetrating through the host cell membrane, as they must be delivered inside the subcellular compartment where the target bacteria reside [9]. Overall, conventional antibiotics have low therapeutic indices, an inability to target intracellular pathogens or reach the site of action, and display wide range of adverse effects [9].

To overcome the limitations of conventional antibiotic delivery, transdermal drug delivery (TDD) technology was introduced in the late 1970s [10]. TDD allows antibiotics to penetrate through the physical skin barrier, i.e., the stratum corneum (SC) and pass through the skin's epidermal and dermal layers, where it's absorbed through diffusion. This mode of delivery is safe, minimally invasive, self-administered, offers a probability of steady-state drug levels, and provides better bioavailability. TDD also allows for sustained drug release, bypasses the first hepatic metabolism, reduces GI side effects, and is patient-compliant [11]. However, passive TDD limits the penetration and absorption of antibiotics of MW > 500 kDa [8]. Therefore, many active techniques were proposed for delivering the antibiotics to the dermal layer by breaching the SC barrier, which resulted in the introduction of microneedles (MNs) [12,13]. MNs are micro-sized miniature needles that facilitate the delivery of antibiotics to the subcutaneous tissues without reaching the nerve endings located in the dermis. Extensive research has been conducted in the area of MNs to bring about the advancement in this promising drug delivery technique [14, 15, 16, 17]. Different materials such as glass, silicon, polymers, etc., have been used to fabricate advanced designs of MN arrays by applying different fabrication methods to enhance the delivery of the antibiotic across the skin layers. This review uniquely focuses on MN systems for antibiotic delivery, a niche yet critical area often overshadowed by MN applications in vaccines or insulin delivery. Unlike prior works, it comprehensively synthesizes advancements in MN designs—including solid, coated, hollow, dissolvable, and smart stimuli-responsive systems—tailored to overcome limitations of conventional antibiotic administration. The review highlights innovative MN-nanomaterial hybrids that enhance drug loading, controlled release, and biofilm penetration, addressing challenges like intracellular pathogen targeting and antibiotic resistance. It critically evaluates preclinical successes against resistant pathogens and chronic wounds, underscoring MN's potential to minimize systemic toxicity and improve bioavailability through localized, pain-free delivery. By consolidating design strategies, material innovations, and translational outcomes, the review bridges gaps between experimental MN platforms and real-world clinical needs.