3D-Printed cannabidiol stent for local treatment of urinary tract infections

Abstract

Urinary tract infections (UTIs) are highly prevalent among women and those assigned female at birth, and frequently necessitate the administration of systemic antibiotics, which contributes to the antibiotic resistance crisis due to overuse and suboptimal patient adherence. This study introduces an innovative 3D-printed stent designed specifically for the localized treatment of UTIs, aiming at reducing systemic drug exposure and lowering recurrence rates. Tailored for the female urethra, the stent consists of a laponite-alginate hydrogel scaffold integrated with cannabidiol (CBD)-loaded PLGA microparticles to facilitate controlled drug release. A Design of Experiments (DoE) approach was utilized to optimize printing parameters, ensuring structural integrity and printability. CBD, known for its analgesic and antimicrobial properties, was added as therapeutic agent. The composite system exhibited prolonged antimicrobial activity against both Gram-positive and Gram-negative bacteria. This localized strategy has the potential to enhance therapeutic effects while reducing the need for systemic administration, which may, in turn, help limit associated side effects and improve patient adherence. The integration of 3D printing technology and controlled drug release signifies a substantial advancement towards more effective and personalized interventions for UTI management.

Introduction

Urinary tract infections (UTIs) rank among the most prevalent bacterial infections affecting women and individuals assigned female at birth throughout various life stages, with nearly one in two women experiencing at least one UTI in their lifetime. (Foxman, 2010) The risk of infection increases with age, contributing to significant morbidity and healthcare costs. (Foxman, 2010) UTIs commonly manifest as discomfort and painful symptoms (Fig. 1A) and occur when bacteria from the perianal region infiltrate the urinary tract. (Flores-Mireles et al., 2015) The increased susceptibility of women to UTIs is primarily attributed to anatomophysiological factors, including a shorter urethra (3–5 cm), its close proximity to the rectum, and hormonal fluctuations that influence the urinary and vaginal microbiota. Additionally, behavioral and environmental factors − such as sexual activity, the frequent use of personal care products and dietary habits − further contribute to the elevated risk of infection. (Foxman, 2010, Antunes-Lopes et al., 2020, Horwitz et al., 2015) Endogenous bacteria from the rectal flora can travel through the fecal-perineal-urethral route, ascend the urethra, and reach the bladder, resulting in infection. (Flores-Mireles et al., 2015, Horwitz et al., 2015, Glover et al., 2014) Pregnancy further enhances susceptibility to UTIs due to hormonal changes, particularly the effect of progesterone, which relaxes the bladder muscles and predisposes individuals to bacterial colonization. (Cellat et al., 2023, Madane et al., 2024) Similarly, postmenopausal women experience a decline in protective Lactobacillus strains, increasing their vulnerability to be affected by UTIs. (Antunes-Lopes et al., 2020, Horwitz et al., 2015).

The urinary tract is traditionally considered a sterile environment due to the absence of uropathogenic bacteria; however, under certain disease conditions, pathogenic microbes can colonize the tract and cause infections, with some strains acquiring or exhibiting uropathogenic characteristics. (Antunes-Lopes et al., 2020, Horwitz et al., 2015, Hogins et al., 2022, Mahesh et al., 2024) Escherichia coli (UPEC) is the most predominant pathogen, responsible for approximately 75 % of UTIs. (Foxman, 2010, Flores-Mireles et al., 2015) The urethral environment is crucial for bacterial proliferation, with factors such as pH significantly affecting bacterial growth and antibiotic efficacy. (Yang et al., 2014) Many commonly prescribed antibiotics exhibit enhanced antibacterial activity in acidic conditions. (Yang et al., 2014, Mahdizade Ari et al., 2023).

Current UTI treatment regimens rely on symptomatic relief and systemic antibiotics. However, the use of systemic antibiotics is associated with side effects and contributes to the alarming rise of antibiotic resistance, a global health concern. (Flores-Mireles et al., 2015, Lin et al., 2025, Aggarwal et al., 2024) Resistance development is aggravated by non-compliance with treatment regimens, overuse and misuse of antibiotics, and the release of antimicrobial agents into the environment. (Aggarwal et al., 2024, Chen et al., 2023) Additional factors include limited antibiotic approvals, high development costs, changes in gut microbiota, and ongoing bacterial exposure to subtherapeutic antibiotic concentrations, all of which further drive resistance mechanisms. (Flores-Mireles et al., 2015, Chen et al., 2023) The escalating resistance crisis threatens effective treatment options, increases healthcare burdens, and leads to fatal outcomes. (Aggarwal et al., 2024, Chen et al., 2023) Consequently, there is an urgent need for novel antimicrobial agents and innovative drug delivery systems that minimize systemic exposure and reduce the development of resistance (Fig. 1B). (Chen et al., 2023).

Cannabidiol (CBD), a bioactive compound derived from Cannabis sativa, possesses analgesic and anti-inflammatory properties. (Cheng et al., 2023, Costa et al., 2007, Berrocoso et al., 2017, Tihăuan et al., 2025) Further, the compound has gained attention for its antimicrobial effects, making it a promising candidate for UTI treatment. (Tihăuan et al., 2025, Gildea et al., 2022, Feldman et al., 2018, Abichabki et al., 2022) In fact, CBD has demonstrated strong antibacterial activity, particularly against Gram-positive bacteria, by damaging bacterial cell walls and membranes and disrupting their integrity. (Feldman et al., 2018, Zeng et al., 2025) Additionally, localized application of CBD can offer therapeutic benefits while bypassing first-pass metabolism, thereby minimizing systemic drug exposure and reducing the risk of developing resistance. (Chen et al., 2023, Cheng et al., 2023, Tihăuan et al., 2025) However, despite evidence supporting CBD’s therapeutic potential, its pharmacological limitations and the absence of advanced delivery systems remain major barriers to broader clinical use. (Moniruzzaman et al., 2024).

Recent advancements have explored the integration of CBD into various drug delivery systems to enhance its therapeutic efficacy and bioavailability. (Tiboni et al., 2021) For instance, Monou et al. developed 3D-printed alginate films incorporating CBD and nanoparticles, demonstrating potential in wound-healing applications. (Monou et al., 2022) Similarly, 3D-printed bigel matrices and buccal films using nanostructured lipid carriers have been reported to improve cannabinoid delivery and patient compliance. (Abdella et al., 2024, Gościniak et al., 2024) In addition, 3D-printed stents with bioactive surfaces and polysaccharide-based carriers loaded with phytochemicals further highlight the versatility of additive manufacturing for localized, sustained drug release. (Lee et al., 2024, Archana et al., 2023).

Here, we propose to enhance localized drug delivery and improve treatment outcomes using a CBD-eluting urethral stent. To ensure extended release, CBD was loaded into biodegradable polymeric microparticles, which were then embedded into a laponite-alginate hydrogel scaffold. This composite material was used to create a soft stent designed to fit the unique anatomy of the female urethra, ensuring sustained antimicrobial action while minimizing systemic side effects, via additive manufacturing, a technology that enables the rapid customization of dosage forms to meet specific patient needs (Teworte et al., 2023, Eugster et al., 2023). Thanks to a Design of Experiments (DoE) approach, we optimized printing parameters and ensured a high-performing ink that allows for the continuous release of CBD, demonstrating antibacterial activity, as proven by our release study in artificial urine and ex vivo tissues.

Download the full article as PDF here 3D-Printed cannabidiol stent for local treatment of urinary tract infections

or read it here

Materials

Formic acid, PLGA Resomer® 502 (PLGA end-capped), PVA Mowiol 8–88, and alginate were purchased from Sigma–Aldrich, St. Louis, USA. Acetonitrile, methanol, and creatinine were sourced from Thermo Fisher Scientific, Waltham, USA. Dichloromethane was purchased at VWR Chemicals, Darmstadt, Germany. CBD was kindly supplied by Cantourage GmbH, Berlin, Germany, and Open Book Extracts, Roxboro, USA. BYK Additives & Instruments, Wesel, Germany, kindly provided Laponite®. TRIS Pufferan > 99.9 %, D (+) saccharose, sodium sulfate, uric acid, mono sodium citrate, urea, potassium chloride, calcium chloride, ammonium chloride, di-potassium oxalate monohydrate, magnesium sulfate, potassium dihydrogen phosphate, di-sodium hydrogen phosphate, Tween 80, sodium phosphate dibasic, potassium phosphate monobasic and sodium chloride were purchased at Carl Roth, Karlsruhe, Germany. Ultrapure water (UPW) from Barnstead Smart2Pure water purification system from Thermo Fisher Scientific. Printing needles (20/22G) and cartridges were bought at Cellink, a Bico Company, Boston, USA. The column used for the HPLC analytics was a Kinetex core–shell technology Xb-C18 150×2.1 mm and particle size 2.6 µm column from Phenomenex, Torrance, USA. The 6-well plates used were bought at TPP, Trasadingen, Switzerland. Bacteria (bacteria strain Escherichia coli W3110 and Staphylococcus aureus Col (MRSA) which is methicillin-resistant), and lysogeny broth were obtained from the Reymond lab, University of Bern, Switzerland.

Remo Eugster, Melanie Santschi, Giorgio Buttitta, Basak Olcay, Jean-Louis Reymond, Simone Aleandri, Paola Luciani,
3D-Printed cannabidiol stent for local treatment of urinary tract infections, International Journal of Pharmaceutics, Volume 680, 2025, 125761, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2025.125761.

Read also our introduction article on The Role of Excipients in CBD Products here: