Needle-free jet injectors (NFJIs) are one of the alternatives to hypodermic needles for transdermal drug delivery. These devices use a high-velocity jet stream to puncture the skin and deposit drugs in subcutaneous tissue. NFJIs typically exhibit two phases of jet injection – namely – an initial peak-pressure phase (< 5 ms), followed by a constant jet speed injection phase (≳ 5 ms). In NFJIs, jet velocity and jet diameter are tailored to achieve the required penetration depth for a particular target tissue (e.g., intradermal, intramuscular, etc.). Jet diameter and jet velocity, together with the injectant volume, guide the design of the NFJI cartridge and thus the required driving pressure. For device manufacturers, it is important to rapidly and accurately estimate the cartridge pressure and jet velocities to ensure devices can achieve the correct operational conditions and reach the target tissue. And thus, we seek to understand how cartridge design and fluid properties affect the jet velocity and pressure profiles in this process. Starting with experimental plunger displacement data, transient numerical simulations were performed to study the jet velocity profile and stagnation pressure profile. We observe that fluid viscosity and cartridge-plunger friction are the two most important considerations in tailoring the cartridge geometry to achieve a given jet velocity. Using empirical correlations for the pressure loss for a given cartridge geometry, we extend the applicability of an existing mathematical approach to accurately predict the jet hydrodynamics. By studying a range of cartridge geometries such as asymmetric sigmoid contractions, we see that the power of actuation sources and nozzle geometry can be tailored to deliver drugs with different fluid viscosities to the intradermal region.
more »
« less
Understanding the effect of counterpressure buildup during syringe injections
The pain felt during injection, typically delivered via a hypodermic needle as a single bolus, is associated with the pressure build-up around the site of injection. It is hypothesized that this counterpressure is a function of the target tissue as well as fluid properties. Given that novel vaccines target different tissues (muscle, adipose, and
skin) and can exhibit a wide range of fluid properties, we conducted a study of the effect of volumetric flow rate, needle size, viscosity and rheology of fluid, and hyaluronidase as an adjuvant on counterpressure build-up in porcine skin and muscle tissues. In particular, we found a significant increase in counterpressure for intradermal (ID) injections compared to intramuscular (IM) injections, by an order of magnitude in some cases. We also
showed that the addition of adjuvant affected the tissue back pressure only in case of subcutaneous (SC) injections. We observed that the volumetric flow rate plays an important role along with the needle size. This study aims to improve the current understanding and limitations of liquid injectability via hypodermic needles, however, the results also have implications for other technologies, such as intradermal jet injection where a liquid bleb is formed under the skin.
more »
« less
- Award ID(s):
- 1749382
- NSF-PAR ID:
- 10312993
- Date Published:
- Journal Name:
- International journal of pharmaceutics
- Volume:
- 602
- ISSN:
- 0378-5173
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
more » « less
Abstract Transdermal drug delivery offers a promising alternative to traditional methods such as oral ingestion and hypodermic injection. Hypodermic injections are painful, while oral ingestion requires higher doses due to enzymatic degradation and poor absorption. While microneedles address the pain issue, they are limited to delivering small amounts of drugs and can be impractical due to peeling off with motion and sweat. Herein, this work proposes soft injectables using drug‐carrying sutures for painless and localized sustained delivery in the dermis. These sutures can remain in place during delivery and are suitable for all skin types. Surgical sutures can also serve as open capillary microfluidic channels carrying drug from a wearable drug reservoir to enable long‐term (weeks to months) transdermal drug delivery. The experiments focus on delivering 5‐fluorouracil (5‐FU), a cancer drug, and rhodamine B, a drug model. A fixed‐length suture of 60 cm delivers 0.43 mg of 5‐flurouracil in 15 min. The experiments also demonstrate a continuous drug delivery of rhodamine B for over 8 weeks at a rate of 0.0195 mL h−1. The results highlight that soft injectable sutures are promising candidates for long‐term sustained delivery of varying quantities of drugs over weeks period compared to hypodermic injection, oral ingestion, or microneedles.
-
Agriculture is facing new challenges, with global warming modifying the survival chances for crops, and new pests on the horizon. To keep up with these challenges, gene delivery provides tools to increase crop yields. On the other hand, gene delivery also opens the door for molecular farming of pharmaceuticals in plants. However, towards increased food production and scalable molecular farming, there remain technical difficulties and regulatory hurdles to overcome. The industry-standard is transformation of plants via Agrobacterium tumefaciens , but this method is limited to certain plants, requires set up of plant growth facilities and fermentation of bacteria, and introduces lipopolysaccharides contaminants into the system. Therefore, alternate methods are needed. Mechanical inoculation and spray methods have already been discussed in the literature – and here, we compare these methods with a newly introduced petiole injection technique. Because our interest lies in the development of plant viruses as immunotherapies targeting human health as well as gene delivery vectors for agriculture applications, we turned toward tobacco mosaic virus as a model system. We studied the effectiveness of three inoculation techniques: mechanical inoculation, Silwet-77 foliar spray and petiole injections. The foliar spray method was optimized, and we used 0.03% Silwet L-77 to induce infection using either TMV or a lysine-added mutant TMV-Lys. We developed a method using a needle-laden syringe to target and inject the plant virus directly into the vasculature of the plant – we tested injection into the stem and petiole. Stem inoculation resulted in toxicity, but the petiole injection technique was established as a viable strategy. TMV and TMV-Lys were purified from single plants and pooled leaf samples – overall there was little variation between the techniques, as measured by TMV or TMV-Lys yields, highlighting the feasibility of the syringe injection technique to produce virus nanoparticles. There was variation between yields from preparation to preparation with mechanical, spray and syringe inoculation yielding 40–141 mg, 36–56 mg, 18–56 mg TMV per 100 grams of leaves. Similar yields were obtained using TMV-Lys, with 24–38 mg, 17–28, 7–36 mg TMV-Lys per 100 grams of leaves for mechanical, spray and syringe inoculation, respectively. Each method has its advantages: spray inoculation is highly scalable and therefore may find application for farming, the syringe inoculation could provide a clean, aseptic, and controlled approach for molecular farming of pharmaceuticals under good manufacturing protocols (GMP) and would even be applicable for gene delivery to plants in space.more » « less
-
Guidelines identifying best practices for harvesting tissues that lead to optimal DNA preservation are few but are important curatorial concerns for genetic resource collections. We conducted a temporal study to establish rate of DNA degradation of tissue samples extracted from field-caught museum specimens. Five individuals of Sigmodon hispidus were collected and their liver and muscle tissues were harvested. Each tissue type was sectioned into 15 subsamples, and each was preserved in liquid nitrogen at different time intervals (2, 4, 8, 16 and 32 minutes; 1, 2, 4, 8 and 16 hours; and 1, 2, 4, 8 and 16 days) following death. DNA was extracted using an automated robotic instrument and molecular mass profiles were determined fluorometrically. Post-mortem DNA degradation was continuous and dependent on time, but also was significantly affected by differences among individual cotton rats. DNA fragments of ≥10,000 base pair in length were present in muscle samples across all time intervals, whereas DNA fragments of this size in liver samples were no longer present after 8 to 16 hours post-mortem. DNA molecular mass profiles showed that muscle samples retained 80% of their longest fragments (≥10,000 bp) until 1 day post-mortem, whereas liver samples retained the same percentage only until 8 minutes after death. Although rates of decay were measured from samples in a laboratory (not field) setting, rates of decay presented here can guide field and museum workers in best practices. Results suggest that opportunistic samples, such as those from roadkill specimens, are more likely to be of use for a variety of molecular methods when muscle is preserved. Considerations of differences in rates of degradation may also guide selection of tissue types housed in genetic resource collections, especially under space-limited circumstances.more » « less
-
more » « less
Abstract Meniscus allograft transplantations (MATs) represent established surgical procedures with proven outcomes. Yet, storage as frozen specimens and limited cellular repopulation may impair graft viability. This proof‐of‐concept study tests the feasibility of injecting allogeneic mesenchymal stromal/stem cells (MSCs) in meniscus allograft tissue. We investigated the injectable cell quantity, survival rate, migration, and proliferation ability of MSCs up to 28 days of incubation. In this controlled laboratory study, seven fresh‐frozen human allografts were injected with human allogeneic MSCs. Cells were labeled and histological characteristics were microscopically imaged up to 28 days. Mock‐injected menisci were included as negative controls in each experiment. Toluidine blue staining demonstrated that a 100‐µl volume can be injected while retracting and rotating the inserted needle. Immediately after injection, labeled MSCs were distributed throughout the injection channel and eventually migrated into the surrounding tissues. Histological assessment revealed that MSCs cluster in disc‐like shapes, parallel to the intrinsic lamination of the meniscus and around the vascular network. Quantification showed that more than 60% of cells were present in horizontally injected grafts and more than 30% were observed in vertically injected samples. On Day 14, cells adopted a spindle‐shaped morphology and exhibited proliferative and migratory behaviors. On Day 28, live/dead ratio assessment revealed an approximately 80% cell survival. The study demonstrated the feasibility of injecting doses of MSCs (>0.1 million) in meniscus allograft tissue with active cell proliferation, migration, and robust cell survival.
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1016/j.ijpharm.2021.120530
