Efficacy and safety of needle-free jet injector-assisted intralesional treatments in dermatology—a systematic review

Drug Delivery and Translational Research https://doi.org/10.1007/s13346-023-01295-x REVIEW ARTICLE Efficacy and safety of needle‑free jet injector‑assisted intralesional treatments in dermatology—a systematic review Vazula Zulfra Bekkers1 · Liora Bik1 · Johanna Catharina van Huijstee1 · Albert Wolkerstorfer2 · Errol Prospero Prens1 · Martijn Bastiaan Adriaan van Doorn1 Accepted: 4 January 2023 © The Author(s) 2023 Abstract Needle-free jet injectors are used for the intralesional treatment of various dermatological indications. However, a systematic review that evaluates the efficacy and safety of these treatments has not been published. The objectives of this study are to evaluate the efficacy and safety of needle-free jet injections for dermatological indications and to provide evidence-based treatment recommendations. An electronic literature search was conducted in April 2022. Two reviewers independently selected studies based on predefined criteria and performed a methodological quality assessment using the Cochrane Collaborations risk-of-bias 2.0 assessment tool and Newcastle–Ottawa Scale. Thirty-seven articles were included, involving 1911 participants. Dermatological indications included scars, alopecia areata, hyperhidrosis, nail diseases, non-melanoma skin cancer, common warts, local anesthesia, and aesthetic indications. Keloids and other types of scars (hypertrophic, atrophic, and burn scars) were investigated most frequently (n = 7). The included studies reported favorable efficacy and safety outcomes for intralesional jet injector-assisted treatment with triamcinolone acetonide/hexacetonide, 5-fluorouracil, bleomycin, or hyaluronic acid. Two high-quality studies showed good efficacy and tolerability of intralesional jet injections with a combination of 5-fluorouracil and triamcinolone acetonide in hypertrophic scars and with saline in boxcar and rolling acne scars. No serious adverse reactions and good tolerability were reported in the included studies. Overall, the methodological quality of the included studies was low. Limited evidence suggests that needle-free jet injector-assisted intralesional treatment is efficacious and safe for hypertrophic and atrophic acne scars. More well-powered RCTs investigating the efficacy and safety of jet injector treatment in dermatology are warranted to make further evidence-based recommendations. Keywords Jet injection · Needle-free injection · Efficacy · Safety · Dermatology · Systematic review Abbreviations 5-ALA 5-Aminolevulinic acid BCC Basal cell carcinoma CCTs Controlled clinical trial DCJIs Disposable cartridge jet injectors GAIS Global Aesthetic Improvement Scale HDSS Hyperhidrosis disease severity scale MB Morbus Bowen MUNJIs Multi-use nozzle jet injectors NAPSI Nail Psoriasis Severity Index NOS Newcastle Ottawa Scale * Vazula Zulfra Bekkers 1 Department of Dermatology, Erasmus Medical Center, Rotterdam, the Netherlands 2 Department of Dermatology, Amsterdam University Medical Center, Location AMC, Amsterdam, the Netherlands PDT Photodynamic therapy PRISMA Preferred Reporting Items for Systematic Reviews and Meta-analyses PROSPERO International Prospective Register of Systematic Reviews RCTs Randomized controlled trial ROB Risk of bias tool Robvis Risk of bias visualization SCC Squamous cell carcinoma TCA Triamcinolone acetonide Introduction Intradermal drug delivery has many advantages over other routes of administration, especially high bioavailability in the skin [1, 2]. Over the past decades, a variety of needle-free devices that enable intradermal drug delivery has been developed, including fractional ablative lasers, 13 Vol.:(0123456789) Drug Delivery and Translational Research iontophoresis, sonophoresis, and various types of mechanical and energy-based jet injectors [3–5]. Jet injectors are commonly used for the intralesional treatment of several dermatological conditions such as keloids, hypertrophic scars, and recalcitrant viral warts [6, 7]. Traditional mechanical jet injectors act with a fixed pressure predetermined by spring size [8]. Innovative electronically controlled pneumatic jet injectors are devices in which volume and pressure can be controlled by accelerated and compressed gas as pressure source, which dispense fluids into the skin [7, 9]. Other types of jet injectors are controlled by Lorentz or piezoelectric actuators, lasers, and shockwaves to pressurize the injected drug [10]. In contemporary healthcare, we are moving towards more patient-centered care. It is important to improve patient comfort and avoid physical or psychological harm as much as possible. According to a previous study, 63% of children and 24% of the adult population in the USA fear needles [11]. This is one of the reasons why jet injectors can be a viable alternative for conventional needles. Needle-free jet injectors can be an attractive alternative for hypodermic needles for patients experiencing needle phobia, minimize treatment-related pain, and are free of risk for needlestick injuries and cross-contamination. Additionally, jet injectors enable accurate and reproducible dermal delivery of liquid drugs and disperse the drug more evenly in the skin than conventional needle injections [7, 9, 12, 13]. At present, there are a few overviews and narrative reviews describing the use of jet injector-assisted intralesional treatment for different dermatological indications [7, 10, 12, 14]. However, a systematic and critical review that evaluates the efficacy and safety of jet injector-assisted intralesional treatment in dermatology is lacking. In this review, we aimed to systematically review and evaluate the quality of clinical evidence for intralesional treatment of dermatological indications using needle-free jet injector systems and provide evidence-based recommendations for clinical practice. Materials and methods A literature search was conducted in April 2022 using Embase, MEDLINE ALL Ovid, Web of Science, and Cochrane Central Register of Controlled Trials databases, to identify relevant publications. This systematic review was registered in the PROSPERO (CRD42021258278) and followed the Preferred Reporting Items for the PRISMA 2020 checklist [15]. Studies were included if they were human studies, written in English, published from inception to April 2022, randomized controlled trials (RCTs), controlled clinical trials (CCTs), prospective or retrospective cohort studies, and case 13 series and included patients of all ages with dermatological indications eligible for intralesional treatment using needlefree jet injectors. Exclusion criteria included studies with fewer than 10 patients and intramuscular or subcutaneous drug delivery. Selection of the articles, standardized data extraction, and methodological quality assessment of the included studies were performed independently by two authors (V.B. and J.V.H.). Articles were screened based on title and abstract. The primary outco (...truncated)