Recent advances in mechanical force-assisted transdermal delivery of macromolecular drugs

Wang, Ruxuan; Bian, Qiong; Xu, Yihua; Xu, Dong; Gao, Jian

doi:10.1016/j.ijpharm.2021.120598

Cited by 20 publications

(16 citation statements)

References 121 publications

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“…High pressure-based or velocity-based delivery devices such as jet injections have recently joined the battery of transdermal delivery enhancement techniques, the need to deliver high amounts of therapeutics at higher speeds having driven the development of such devices [14,39]. An attractive alternative to needle-based injection, the needle-free jet injector is a device that generates high-speed (120-200 m/s) jets of either powder or liquid jet injections that puncture the skin and deliver drugs using a power source such as compressed gas or a spring [14,272]. Although jet injections rupture the epidermal layer, which is reversible in nature [273], this technique is known to be painless and noninvasive [14].…”

Section: High Pressure-based Devicesmentioning

confidence: 99%

“…The liquid jet injector consists of a compartment (drug reservoir) which holds a drug formulation, a piston, a power source such as a spring or compressed gas, and an actuation mechanism consisting of a piezoelectric transducer which controls liquid delivery volume and injection velocity (Figure 7A) [275]. To deliver the drug formulation, the liquid within the compartment is compressed and pushed through a narrow orifice of 100 to 300 µm diameter [272]. By varying the jet velocity and orifice diameter, the jet injector can transport drug molecules intradermally, subcutaneously, or intramuscularly [14].…”

Section: High Pressure-based Devicesmentioning

confidence: 99%

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Beneath the Skin: A Review of Current Trends and Future Prospects of Transdermal Drug Delivery Systems

et al. 2022

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The ideal drug delivery system has a bioavailability comparable to parenteral dosage forms but is as convenient and easy to use for the patient as oral solid dosage forms. In recent years, there has been increased interest in transdermal drug delivery (TDD) as a non-invasive delivery approach that is generally regarded as being easy to administer to more vulnerable age groups, such as paediatric and geriatric patients, while avoiding certain bioavailability concerns that arise from oral drug delivery due to poor absorbability and metabolism concerns. However, despite its many merits, TDD remains restricted to a select few drugs. The physiology of the skin poses a barrier against the feasible delivery of many drugs, limiting its applicability to only those drugs that possess physicochemical properties allowing them to be successfully delivered transdermally. Several techniques have been developed to enhance the transdermal permeability of drugs. Both chemical (e.g., thermal and mechanical) and passive (vesicle, nanoparticle, nanoemulsion, solid dispersion, and nanocrystal) techniques have been investigated to enhance the permeability of drug substances across the skin. Furthermore, hybrid approaches combining chemical penetration enhancement technologies with physical technologies are being intensively researched to improve the skin permeation of drug substances. This review aims to summarize recent trends in TDD approaches and discuss the merits and drawbacks of the various chemical, physical, and hybrid approaches currently being investigated for improving drug permeability across the skin.

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Section: High Pressure-based Devicesmentioning

confidence: 99%

Section: High Pressure-based Devicesmentioning

confidence: 99%

Beneath the Skin: A Review of Current Trends and Future Prospects of Transdermal Drug Delivery Systems

et al. 2022

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“…Some examples of these effects include (i) increase in the paracellular permeability as a consequence of rearrangement of the intercellular junctions; and (ii) enhancement of molecular permeation across cell membranes and intracellular accumulation as a result of pore formation (sonoporation) or enhanced endocytosis [ 8 , 9 ]. These effects have been exploited to increase the permeability of the BRB [ 10 , 11 , 12 ], the BBB [ 8 , 13 ] (including some clinical trials NCT03119961, NCT04417088, NCT04440358, NCT04528680), the blood-labyrinth barrier in the ear [ 14 , 15 ], and the skin barrier (epidermis) [ 16 , 17 , 18 , 19 ] for a variety of materials (small molecule drugs, antibodies, nanoparticles) that otherwise have limited permeation in these barriers. These studies focused on the importance of a single physicochemical feature of a drug, the molecular weight.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Microbubble-Assisted Ultrasound on Molecular Permeability across Cell Barriers

et al. 2022

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The combination of ultrasound and microbubbles (USMB) has been applied to enhance drug permeability across tissue barriers. Most studies focused on only one physicochemical aspect (i.e., molecular weight of the delivered molecule). Using an in vitro epithelial (MDCK II) cell barrier, we examined the effects of USMB on the permeability of five molecules varying in molecular weight (182 Da to 20 kDa) and hydrophilicity (LogD at pH 7.4 from 1.5 to highly hydrophilic). Treatment of cells with USMB at increasing ultrasound pressures did not have a significant effect on the permeability of small molecules (molecular weight 259 to 376 Da), despite their differences in hydrophilicity (LogD at pH 7.4 from −3.2 to 1.5). The largest molecules (molecular weight 4 and 20 kDa) showed the highest increase in the epithelial permeability (3-7-fold). Simultaneously, USMB enhanced intracellular accumulation of the same molecules. In the case of the clinically relevant anti- C-X-C Chemokine Receptor Type 4 (CXCR4) nanobody (molecular weight 15 kDa), USMB enhanced paracellular permeability by two-fold and increased binding to retinoblastoma cells by five-fold. Consequently, USMB is a potential tool to improve the efficacy and safety of the delivery of drugs to organs protected by tissue barriers, such as the eye and the brain.

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“…In fact, commercially available injectors that are capable of producing such pressure peaks can routinely deliver 0.1 to 1 mL of fluid at depths greater than 10 mm. For summary, a number of recent review articles on this technology and its state-of-the-art can be found in the literature, e.g., [1][2][3][4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Design and Analysis: Servo-Tube-Powered Liquid Jet Injector for Drug Delivery Applications

Portaro

2022

Applied Sciences

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The current state of commercially available needle-free liquid jet injectors for drug delivery offers no way of controlling the output pressure of the device in real time, as the driving mechanism for these injectors provides a fixed delivery pressure profile. In order to improve the delivery efficiency as well as the precision of the targeted tissue depth, it is necessary to develop a power source that can accurately control the plunger velocity. The duration of a liquid jet injection can vary from 10 to 100 ms, and it generate acceleration greater than 2 g (where g is the gravity); thus, a platform for real-time control must exhibit a response time greater than 1 kHz and good accuracy. Improving the pioneering work by Taberner and others whereby a Lorentz force actuator based upon a voice coil is designed, this study presents a prototype injector system with greater controllability based on the use of a fully closed-loop control system and a classical three-phase linear motor consisting of three fixed coils and multiple permanent magnets. Apart from being capable of generating jets with a required stagnation pressure of 15–16 MPa for skin penetration and liquid injection, as well as reproducing typical injection dynamics using commercially available injectors, the novelty of this proposed platform is that it is proven to be capable of shaping the real-time jet injection pressure profile, including pulsed injection, so that it can later be tailored for more efficient drug delivery.

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Recent advances in mechanical force-assisted transdermal delivery of macromolecular drugs

Cited by 20 publications

References 121 publications

Beneath the Skin: A Review of Current Trends and Future Prospects of Transdermal Drug Delivery Systems

Beneath the Skin: A Review of Current Trends and Future Prospects of Transdermal Drug Delivery Systems

The Effect of Microbubble-Assisted Ultrasound on Molecular Permeability across Cell Barriers

Design and Analysis: Servo-Tube-Powered Liquid Jet Injector for Drug Delivery Applications

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