Micromolding of Thermoplastic Polymers for Direct Fabrication of Discrete, Multilayered Microparticles

Sadeghi, Ilin; Lu, Xueguang; Sarmadi, Morteza; Langer, Robert; Jaklenec, Ana

doi:10.1002/smtd.202200232

Cited by 9 publications

(6 citation statements)

References 67 publications

(64 reference statements)

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“…In order to determine in vivo release kinetics, we employed an In Vivo Imaging System (IVIS, PerkinElmer, Hopkinton, MA) to track the release of a fluorescent payload from PULSED microparticles. We validated a previously existing in vivo quantification method, [31,36,40] by monitoring the release of Alexa Fluor 647-labeled 10 kDa dextran from PLGA particles incubated in a 96-well plate. As previously demonstrated, fluorescent signal was not detected until the release of the Alexa Fluor 647-labeled 10 kDa dextran, likely due to the high concentration of the dye self-quenching prior to release.…”

Section: Resultsmentioning

confidence: 99%

A Scalable Platform for Fabricating Biodegradable Microparticles with Pulsatile Drug Release

et al. 2023

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Despite the success of therapeutics and prophylactics in prolonging life and improving quality of life, these benefits are limited by poor patient adherence, which can be as low as 50% in patients with chronic conditions. [3][4][5] This lack of patient adherence contributes to negative outcomes, including death, and results in an additional $289 billion in healthcare costs each year in the United States alone. [6][7][8] Reducing drug dosing frequency has been identified as one of the most effective means to increase patient adherence. [9,10] However, many diseases including diabetes, cancer, human immunodeficiency virus infection, depression, and autoimmune disorders, are typically treated with frequent, repeated, and longterm administration of therapeutics, often as frequently as multiple times a day, to maintain drug levels that are both safe and effective. Controlled drug delivery systems represent a promising solution to mitigate compliance issues. By releasing drugs over an extended period of time, these systems can be administered less frequently, thereby improving adherence and patient outcomes. For example, the FDA-approved Lupron Depot, composed of drug-loaded biodegradable microspheres, has been shown to improve patient adherence and convenience by reducing administration frequency from a once-daily injection to one injection every one to six months. [11,12] Oral delivery systems are convenient, but their rapid passage through the gastrointestinal tract limits their duration of action, often requiring frequent re-dosing that can lead to lower levels of patient adherence compared to less frequent parenteral injection(s). [13] Unfortunately, most injectable controlled-release systems generate an initial burst release followed by first-order release kinetics in which drug is released at a perpetually lower rate over time. [14,15] Although these devices extend the duration of drug activity, their front-loaded and slowing rate of release limits their ability to maintain therapeutic efficacy over a long period of time, especially when the biological half-life of the drug is short or the therapeutic window is small. Increasing initial drug loading can extend the duration of release in these Pulsatile drug delivery systems have the potential to improve patient adherence and therapeutic efficacy by providing a sequence of doses in a single injection. Herein, a novel platform, termed Particles Uniformly Liquified and Sealed to Encapsulate Drugs (PULSED) is developed, which enables the high-throughput fabrication of microparticles exhibiting pulsatile release. In PULSED, biodegradable polymeric microstructures with an open cavity are formed using high-resolution 3D printing and soft lithography, filled with drug, and sealed using a contactless heating step in which the polymer flows over the orifice to form a complete shell around a drug-loaded core. Poly(lactic-co-glycolic acid) particles with this structure can rapidly release encapsulated material after delays of 10 ± 1, 15 ± 1, 17 ± 2, or 36 ± 1 days in vivo, ...

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Section: Resultsmentioning

confidence: 99%

A Scalable Platform for Fabricating Biodegradable Microparticles with Pulsatile Drug Release

et al. 2023

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“…These methods usually utilize hard or semi-hard templates with defined geometry of a given size and shape to form polymeric microparticles. In some approaches, microstructures like vaterite particles, micelles, or other micro particulates can serve as a template on which polymer coating could be deposited by the electrostatic or other bonding forces [20][21][22][23][24][25].…”

Section: Template-based Methodsmentioning

confidence: 99%

Template-Free Manufacturing of Defined Structure and Size Polymeric Microparticles

Abdurashitov,

Proshin,

Sukhorukov

2023

Nanomaterials

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Complex-structured polymeric microparticles hold significant promise as an advance in next-generation medicine mostly due to demand from developing targeted drug delivery. However, the conventional methods for producing these microparticles of defined size, shape, and sophisticated composition often face challenges in scalability, reliance on specialized components such as micro-patterned templates, or limited control over particle size distribution and cargo (functional payload) release kinetics. In this study, we introduce a novel and reliably scalable approach for manufacturing microparticles of defined structures and sizes with variable parameters. The concept behind this method involves the deposition of a specific number of polymer layers on a substrate with low surface energy. Each layer can serve as either the carrier for cargo or a programmable shell-former with predefined permeability. Subsequently, this layered structure is precisely cut into desired-size blanks (particle precursors) using a laser. The manufacturing process is completed by applying heat to the substrate, which results in sealing the edges of the blanks. The combination of the high surface tension of the molten polymer and the low surface energy of the substrate enables the formation of discrete particles, each possessing semi-spherical or other designed geometries determined by their internal composition. Such anisotropic microparticles are envisaged to have versatile applications.

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“…Microfluidic can be conveniently combined with the UV-lithography technique for continuously synthesizing microparticles featuring a variety of different shapes and sizes [ 89 , 90 ]. Recent advances in micro/nanotechnology have also allowed for the fabrication of microparticles made of thermoplastic polymers with uniform sizes and well-defined shapes and compositions, providing new building block libraries for modular TE and load bearing applications [ 91 ]. As shown in Figure 3 , micro-modules can incorporate cells (microscaffolds), or may be achieved by the direct assembly of cells (tissue spheroids) [ 92 , 93 ].…”

Section: Cad Assembly Of Cell-free and Cell Laden Micro-modules To Me...mentioning

confidence: 99%

Review on Bioinspired Design of ECM-Mimicking Scaffolds by Computer-Aided Assembly of Cell-Free and Cell Laden Micro-Modules

Salerno

Netti

2023

JFB

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Tissue engineering needs bioactive drug delivery scaffolds capable of guiding cell biosynthesis and tissue morphogenesis in three dimensions. Several strategies have been developed to design and fabricate ECM-mimicking scaffolds suitable for directing in vitro cell/scaffold interaction, and controlling tissue morphogenesis in vivo. Among these strategies, emerging computer aided design and manufacturing processes, such as modular tissue unit patterning, promise to provide unprecedented control over the generation of biologically and biomechanically competent tissue analogues. This review discusses recent studies and highlights the role of scaffold microstructural properties and their drug release capability in cell fate control and tissue morphogenesis. Furthermore, the work highlights recent advances in the bottom-up fabrication of porous scaffolds and hybrid constructs through the computer-aided assembly of cell-free and/or cell-laden micro-modules. The advantages, current limitations, and future challenges of these strategies are described and discussed.

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Micromolding of Thermoplastic Polymers for Direct Fabrication of Discrete, Multilayered Microparticles

Cited by 9 publications

References 67 publications

A Scalable Platform for Fabricating Biodegradable Microparticles with Pulsatile Drug Release

A Scalable Platform for Fabricating Biodegradable Microparticles with Pulsatile Drug Release

Template-Free Manufacturing of Defined Structure and Size Polymeric Microparticles

Review on Bioinspired Design of ECM-Mimicking Scaffolds by Computer-Aided Assembly of Cell-Free and Cell Laden Micro-Modules

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