A resistance-sensing mechanical injector for the precise delivery of liquids to target tissue

Abstract

The precision of the delivery of therapeutics to the desired injection site by using syringes and hollow needles typically depends on the operator. Here, we introduce a highly sensitive, completely mechanical and cost-effective injector for targeting tissue reliably and precisely. As the operator pushes on the syringe plunger, the injector senses the loss-of-resistance on encountering a softer tissue or a cavity, stops advancing the needle, and delivers the payload. We demonstrate that the injector can reliably deliver liquids to the suprachoroidal space — a challenging injection site that provides access to the back of the eye — for a wide range of eye sizes, scleral thicknesses and intraocular pressures, and to target sites relevant for epidural injections, subcutaneous injections and intraperitoneal access. The design of this simple and effective injector can be adapted for a broad variety of clinical applications.

Modeling, design, and machine learning-based framework for optimal injectability of microparticle-based drug formulations

“…S3 and table S1). To this end, two sets of experiments based on L 18 Taguchi orthogonal array were designed and conducted for a 1-ml and a 3-ml syringe with different design factors/levels (tables S2 and S3).…”

“…Multiple designs and manufacturing techniques have been used to fabricate microparticles with a range of sizes and functionality (5)(6)(7)(8)(9), and various release kinetics can be obtained by modulating morphology, material composition, or active perturbation of the drug carrier (4)(5)(6)(7)(8)(9)(10)(11). However, administration of microparticles and biomaterials via an injection holds several challenges (12)(13)(14)(15)(16)(17)(18). Depending on the application, the design of drug delivery systems may prioritize release kinetics, biocompatibility, or other factors that may conflict with optimal parameters used in parenteral injection, especially in subcutaneous administration (i.e., needle gauge, particle size, shape, and concentration) (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22).…”

“…However, administration of microparticles and biomaterials via an injection holds several challenges (12)(13)(14)(15)(16)(17)(18). Depending on the application, the design of drug delivery systems may prioritize release kinetics, biocompatibility, or other factors that may conflict with optimal parameters used in parenteral injection, especially in subcutaneous administration (i.e., needle gauge, particle size, shape, and concentration) (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Injectable microparticle formulations have been translated to the clinic for several controlled release drug applications (12,23).…”

Understanding the In Vivo Fate of Advanced Materials by Imaging

“…They found good co-localization of the stem cells with the collagen ECM (imaged by SHG) in the SCS. This site-specific delivery was also evaluated with micro computed tomography (µCT) [99] (Figure 3). OCT is routinely used in the clinic to image the eye, and has been used to evaluate the interaction between intravitreally injected poly(lactic-coglycolic acid) (PLGA) micromaterials [100] or surgically introduced Argus II medical implants [101,102] with the retina (Figure 4).…”

“…Adapted with permission. [99] Copyright 2019, Springer Nature Limited. hybridization, and mass spectrometry approaches.…”