An Implantable Micro-Caged Device for Direct Local Delivery of Agents

Abstract

Local and controlled delivery of therapeutic agents directly into focally afflicted tissues is the ideal for the treatment of diseases that require direct interventions. However, current options are obtrusive, difficult to implement, and limited in their scope of utilization; the optimal solution requires a method that may be optimized for available therapies and is designed for exact delivery. To address these needs, we propose the Biocage, a customizable implantable local drug delivery platform. The device is a needle-sized porous container capable of encasing therapeutic molecules and matrices of interest to be eluted into the region of interest over time. The Biocage was fabricated using the Nanoscribe Photonic Professional GT 3D laser lithography system, a two-photon polymerization (2PP) 3D printer capable of micron-level precision on a millimeter scale. We demonstrate the build consistency and features of the fabricated device; its ability to release molecules; and a method for its accurate, stable delivery in mouse brain tissue. The Biocage provides a powerful tool for customizable and precise delivery of therapeutic agents into target tissues.

Advanced implantable drug delivery technologies: transforming the clinical landscape of therapeutics for chronic diseases

“…(b) Biocage device boxed in orange in relation to pencil tip and dime to appreciate its minute size and how it can be inserted using a 22-gauge needle. (Image 2B adapted from (Son et al 2017) licensed under CC BY 4.0). c Vantas® and SUPPRELIN® LA 50 mg histrelin acetate implants for prostate cancer symptom relief and childhood central precocious puberty treatment, respectively (Image reproduced from (Rudlang and Brasso 2016).…”

“…By contrast, biodegradable implants use naturally occurring polymers (e.g., human serum albumin, collagen, gelatin) or synthetic polymers (e.g., polylactic acid, polyglycolic acid, polylactic-co-glycolic acid copolymer) (Kumar and Pillai 2018;Yang and Pierstorff 2012). Son et al (2017) developed a 3D-printed porous cylindrical device called Biocage that can be filled with a drug. The Biocage is small enough to fit inside a 22-gauge needle for direct delivery and robust enough to be implanted directly into the target issue.…”

3D Printing in Drug Delivery Systems

“…Chitosan-based magnetic swimmers were fabricated to provide light-triggered doxorubicin drug release in a controlled manner [19]. A porous cylindrical cage with dimensions of 0.34 × 0.9 mm (d × h) was fabricated with the aim of generating a controlled and localized drug delivery device [20]. Fluorescent particles were loaded into an agarose gel inside the cylinder which was then capped with cyanoacrylates.…”

3-D Printed Biocompatible Micro-Bellows Membranes

“…Especially, the introduction of the two-photon polymerization (TPP) technique allowed 3D printing to overcome the micrometer barrier, achieving a resolution in the nanometer range [14], [15]. TPP was employed in different domains such as microelectromechanical systems [16], biomedical devices [17], [18], micro-photonics and imaging [19], [20], and tissue engineering [21]- [23]. Although this technology offers a very high resolution, it has been used to fabricate structures having a dimension in the millimeter scale and feature size in the micrometer resolution [18]- [23].…”