Mechanics of needle-free drug delivery

Despite its long history and widespread applications, needle-free jet injection remains under-utilized in healthcare systems and the detailed mechanism of needle-free injection is poorly understood. Enhanced understanding of needle-free injection may improve clinical outcomes by informing evidence-based techniques. Increased uptake may then benefit clinicians by eliminating the risk of needle-stick injuries and transfection. Patients will benefit from a pain-free alternative, potentially avoiding complications such as needle phobia, which may result in avoidance of necessary medical procedures.In the present study, a needle-free liquid jet injection (NFLJI) device (MED-Jet, MIT Canada Inc., 80-220 psi supply pressure, orifice diameter 120 μm) was characterized for application in dental local anesthesia. A tissue phantom was first devised to mimic porcine oral tissue. The mechanical properties and porosity of fresh tissue were measured using torsional rheometry and scanning electron microscopy, respectively. Candidate phantom materials included hydrogels of type-II bovine gelatin, glycol chitosan and polyhydroxyethylmethacrylate (pHEMA), and type-II bovine gelatin cryogel. The phantom was then used to compare needle injection and NFLJI via a test apparatus comprising a strain gauge transducer, linear motorized traverse, and high-speed camera. Effects of various parameters on injection forces and wound morphology were then characterized, including injection volume (0.1-1 mL) and pneumatic supply pressure (413.7-1241.1 kPa) for NFLJI; and insertion speed (2-37.5 mm/s), needle geometry (18-27 gauge, flat and beveled tips), injection volume (0.3-1 mL), and volumetric flow rate (0.9-7.2 mL/minute) for needle injection. Type-II bovine gelatin (5% mass concentration) provided a reasonable facsimile for the storage modulus and viscosity of porcine oral tissue. The wound morphology in gelatin, however, differed from that of tissue. A porous pHEMA phantom was then found to mimic the mechanical and porous characteristics of porcine oral mucosa, facilitating a wound morphology which better approximated that of injection into tissue. The characteristics of needle insertion, needle injection, and NFLJI were investigated in gelatin and pHEMA phantoms. In needle insertion, increased needle gauge and beveled tip geometry corresponded with decreased insertion forces and fracture toughness. The observed relationship between insertion speed and force amplitude was nonlinear and warrants further investigation in silico. In needle injection, increased volume corresponded with greater force amplitude and impulse, while the relationship between injection volume and work was non-linear. Increased volumetric flow rate correlated with decreased impulse and increased work. Finally, for NFLJI it was found that increased injection volume produced increased force amplitude, impulse, and work. Increased pneumatic supply pressure correlated with greater impulse, work, and force amplitude at volumes of 0.1 mL and 0.3 mL. Increased pneumatic supply pressure also correlated with increased penetration depth of the jet.In comparing needle injection and NFLJI, injection force amplitudes were comparable but the duration of NFLJI was significantly shorter. Additionally NFLJI produced vibrations, absent in needle injection, which should be explored in future work. In comparing the energy delivered to the phantom, for most configurations a 1 mL injection produced greater energy when delivered via NFLJI. This may indicate greater tissue damage. However, clinical investigations have found decreased injection pain associated with NFLJI, indicating that temporal aspects of injection pain sensation may be more relevant than energetic aspects. The results of this investigation are informing clinical pilot testing of NFLJI for local anesthesia at the McGill Dental Clinic. They will help define best clinical practices for the widespread use of needle-free jet injection

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