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1. Biodegradable 3D printed polymer microneedles for transdermal drug delivery

   https://doi.org/10.1039/c8lc00098k  

   Luzuriaga, Michael A.; Berry, Danielle R.; Reagan, John C.; Smaldone, Ronald A.; Gassensmith, Jeremiah J. (January 2018, Lab on a Chip)

   Biodegradable polymer microneedle (MN) arrays are an emerging class of transdermal drug delivery devices that promise a painless and sanitary alternative to syringes; however, prototyping bespoke needle architectures is expensive and requires production of new master templates. Here, we present a new microfabrication technique for MNs using fused deposition modeling (FDM) 3D printing using polylactic acid, an FDA approved, renewable, biodegradable, thermoplastic material. We show how this natural degradability can be exploited to overcome a key challenge of FDM 3D printing, in particular the low resolution of these printers. We improved the feature size of the printed parts significantly by developing a post fabrication chemical etching protocol, which allowed us to access tip sizes as small as 1 μm. With 3D modeling software, various MN shapes were designed and printed rapidly with custom needle density, length, and shape. Scanning electron microscopy confirmed that our method resulted in needle tip sizes in the range of 1–55 μm, which could successfully penetrate and break off into porcine skin. We have also shown that these MNs have comparable mechanical strengths to currently fabricated MNs and we further demonstrated how the swellability of PLA can be exploited to load small molecule drugs and how its degradability in skin can release those small molecules over time. 

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2. 3D‐Printed Microinjection Needle Arrays via a Hybrid DLP‐Direct Laser Writing Strategy

   https://doi.org/10.1002/admt.202201641  

   Sarker, Sunandita; Colton, Adira; Wen, Ziteng; Xu, Xin; Erdi, Metecan; Jones, Anthony; Kofinas, Peter; Tubaldi, Eleonora; Walczak, Piotr; Janowski, Miroslaw; et al (February 2023, Advanced Materials Technologies)

   Abstract Microinjection protocols are ubiquitous throughout biomedical fields, with hollow microneedle arrays (MNAs) offering distinctive benefits in both research and clinical settings. Unfortunately, manufacturing‐associated barriers remain a critical impediment to emerging applications that demand high‐density arrays of hollow, high‐aspect‐ratio microneedles. To address such challenges, here, a hybrid additive manufacturing approach that combines digital light processing (DLP) 3D printing with “ex situ direct laser writing (esDLW)” is presented to enable new classes of MNAs for fluidic microinjections. Experimental results foresDLW‐based 3D printing of arrays of high‐aspect‐ratio microneedles—with 30 µm inner diameters, 50 µm outer diameters, and 550 µm heights, and arrayed with 100 µm needle‐to‐needle spacing—directly onto DLP‐printed capillaries reveal uncompromised fluidic integrity at the MNA‐capillary interface during microfluidic cyclic burst‐pressure testing for input pressures in excess of 250 kPa (n = 100 cycles). Ex vivo experiments perform using excised mouse brains reveal that the MNAs not only physically withstand penetration into and retraction from brain tissue but also yield effective and distributed microinjection of surrogate fluids and nanoparticle suspensions directly into the brains. In combination, the results suggest that the presented strategy for fabricating high‐aspect‐ratio, high‐density, hollow MNAs could hold unique promise for biomedical microinjection applications. 

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3. Design of Topical Ocular Ciprofloxacin Nanoemulsion for the Management of Bacterial Keratitis

   https://doi.org/10.3390/ph14030210  

   Youssef, Ahmed Adel; Cai, Chuntian; Dudhipala, Narendar; Majumdar, Soumyajit (March 2021, Pharmaceuticals)

   Bacterial keratitis (BK) is a critical ocular infection that can lead to serious visual disability. Ciprofloxacin (CIP), moxifloxacin (MOX), and levofloxacin (LFX) have been accepted as monotherapies by the US Food and Drug Administration for BK treatment. CIP is available commercially at 0.3% w/v concentration as an ophthalmic solution and as an ointment for ocular delivery. Because of solubility issues at physiological pH, CIP precipitation can occur at the corneal surface post instillation of the solution dosage form. Consequently, the ocular bioavailability of CIP is reduced. The ointment dosage form is associated with side effects such as blurred vision, itching, redness, eye discomfort, and eye dryness. This study aimed to design a CIP loaded nanoemulsion (NE; CIP-NE) to facilitate drug penetration into the corneal layers for improved therapeutic outcomes as well as to overcome the drawbacks of the current commercial ophthalmic formulations. CIP-NE formulations were prepared by hot homogenization and ultrasonication, using oleic acid (CIP-O-NE) and Labrafac® Lipophile WL 1349 (CIP-L-NE) as the oily phase, and Tween® 80 and Poloxamer 188 as surfactants. Optimized CIP-NE was further evaluated with respect to in vitro release, ex vivo transcorneal permeation, and moist heat sterilization process, using commercial CIP ophthalmic solution as a control. Optimized CIP-O-NE formulation showed a globule size, polydispersity index, and zeta potential of 121.6 ± 1.5 nm, 0.13 ± 0.01, and −35.1 ± 2.1 mV, respectively, with 100.1 ± 2.0% drug content and was spherical in shape. In vitro release and ex vivo transcorneal permeation studies exhibited sustained release and a 2.1-fold permeation enhancement, respectively, compared with commercial CIP ophthalmic solution. Autoclaved CIP-O-NE formulation was found to be stable for one month (last time-point tested) at refrigerated and room temperature. Therefore, CIP-NE formulation could serve as an effective delivery system for CIP and could improve treatment outcomes in BK. 

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4. 3D Printing of Succulent‐Inspired Microneedle Array for Enhanced Tissue Adhesion and Controllable Drug Release

   https://doi.org/10.1002/admt.202400216  

   Sun, Yazhi; Wang, Xiaocheng; Tang, Min; Melarkey, Mary_K; Lu, Ting‐yu; Xiang, Yi; Chen, Shaochen (May 2024, Advanced Materials Technologies)

   Abstract Controllable and long‐term release remains a great challenge in current drug delivery systems. Benefiting from their efficient drug loading and painless administration, microneedles (MNs) have emerged as a promising platform for transdermal drug delivery, while they often fail to achieve long‐term tissue adhesion and controllable extended drug release. Here, 3D printing of an innovative MN patch is presented with succulent‐inspired responsive microstructures and light‐controllable long‐term release capability. The MN exhibits a reversible shrink‐swell volume change behavior in response to surrounding humidity, which enables sufficient mechanical strength for skin penetration under the shrinkage conditions and efficient long‐term adhesion when swollen in skin tissues. Moreover, the MN patch introduces a controllable long‐term drug release system, achieved through the integration of thiolated heparin (Hep‐SH) for sustained growth factor release and graphene oxide (GO) nanosheets for controlled drug release via near infrared (NIR) laser irradiation. The MN patches with growth factor loading have good biocompatibility and can promote the proliferation, migration, and proangiogenesis of endothelial cells is further demonstrated. Thus, it is believed that such flexible MN patches can be promising candidates for controllable long‐term transdermal drug delivery as well as other related tissue engineering applications. 

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5. Enhancing Penetration Performance and Drug Delivery of Polymeric Microneedles Using Silica Nanoparticle Coatings

   https://doi.org/10.1002/admi.202400212  

   Kim, Sohyun; Choi, Hyewon; Jeong, Hyejoong; Ortiz, Wilfredo_Méndez; Cheon, Hwayeong; Jeon, Jae_Yong; Lee, Jae_Hyeon; Han, Jeong_Hwan; Stebe, Kathleen_J; Lee, Daeyeon; et al (June 2024, Advanced Materials Interfaces)

   Abstract Microneedle (MN) technology offers a powerful approach for transdermal delivery enabling painless injection and facilitating self‐administration without the need for professional assistance. However, the weak mechanical strength of MNs can lead to inefficient drug delivery and serious skin irritation if the MNs fracture during administration and leave fragments under the skin. Thus, the MNs need to be mechanically robust to avoid fracture during penetration through the skin while maintaining efficient drug delivery. Herein, the polymer‐based MNs with layer‐by‐layer (LbL) films of silica (SiO₂) nanoparticles (NPs) and a polycation (poly(diallyldimethylammonium chloride) (PDADMAC)) followed by hydrothermal calcination are reinforced. The mechanical strength of the MNs is significantly improved after LbL assembly and shows lower threshold pressure to penetrate skins. Moreover, their drug loading and releasing properties are significantly enhanced due to an increase in the surface area and interfacial interaction. These SiO₂nanoparticle‐containing LbL thin films have great potential for the surface modification of 3D microstructured devices such as MNs, as evidenced by their enhanced mechanical strength and drug coating efficiency that result in a promising MN drug delivery model. 

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