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      Edible Matrix Code with Photogenic Silk Proteins

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          Abstract

          Counterfeit medicines are a healthcare security problem, posing not only a direct threat to patient safety and public health but also causing heavy economic losses. Current anticounterfeiting methods are limited due to the toxicity of the constituent materials and the focus of secondary packaging level protections. We introduce an edible, imperceptible, and scalable matrix code of information representation and data storage for pharmaceutical products. This matrix code is digestible as it is composed of silk fibroin genetically encoded with fluorescent proteins produced by ecofriendly, sustainable silkworm farming. Three distinct fluorescence emission colors are incorporated into a multidimensional parameter space with a variable encoding capacity in a format of matrix arrays. This code is smartphone-readable to extract a digitized security key augmented by a deep neural network for overcoming fabrication imperfections and a cryptographic hash function for enhanced security. The biocompatibility, photostability, thermal stability, long-term reliability, and low bit error ratio of the code support the immediate feasibility for dosage-level anticounterfeit measures and authentication features. The edible code affixed to each medicine can serve as serialization, track and trace, and authentication at the dosage level, empowering every patient to play a role in combating illicit pharmaceuticals.

          Abstract

          An edible code affixed to each medicine offers anticounterfeit measures and authentication features at the dosage level, empowering every patient to play a role in combating illicit pharmaceuticals.

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          Most cited references113

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          Drug delivery and nanoparticles: Applications and hazards

          The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s) may or may not be soluble in biological matrices, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation for the preparation of nanoparticles for drug delivery, varying from biological substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles. It is obvious that the potential interaction with tissues and cells, and the potential toxicity, greatly depends on the actual composition of the nanoparticle formulation. This paper provides an overview on some of the currently used systems for drug delivery. Besides the potential beneficial use also attention is drawn to the questions how we should proceed with the safety evaluation of the nanoparticle formulations for drug delivery. For such testing the lessons learned from particle toxicity as applied in inhalation toxicology may be of use. Although for pharmaceutical use the current requirements seem to be adequate to detect most of the adverse effects of nanoparticle formulations, it can not be expected that all aspects of nanoparticle toxicology will be detected. So, probably additional more specific testing would be needed.
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            Materials fabrication from Bombyx mori silk fibroin.

            Silk fibroin, derived from Bombyx mori cocoons, is a widely used and studied protein polymer for biomaterial applications. Silk fibroin has remarkable mechanical properties when formed into different materials, demonstrates biocompatibility, has controllable degradation rates from hours to years and can be chemically modified to alter surface properties or to immobilize growth factors. A variety of aqueous or organic solvent-processing methods can be used to generate silk biomaterials for a range of applications. In this protocol, we include methods to extract silk from B. mori cocoons to fabricate hydrogels, tubes, sponges, composites, fibers, microspheres and thin films. These materials can be used directly as biomaterials for implants, as scaffolding in tissue engineering and in vitro disease models, as well as for drug delivery.
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              Silk-based biomaterials.

              Silk from the silkworm, Bombyx mori, has been used as biomedical suture material for centuries. The unique mechanical properties of these fibers provided important clinical repair options for many applications. During the past 20 years, some biocompatibility problems have been reported for silkworm silk; however, contamination from residual sericin (glue-like proteins) was the likely cause. More recent studies with well-defined silkworm silk fibers and films suggest that the core silk fibroin fibers exhibit comparable biocompatibility in vitro and in vivo with other commonly used biomaterials such as polylactic acid and collagen. Furthermore, the unique mechanical properties of the silk fibers, the diversity of side chain chemistries for 'decoration' with growth and adhesion factors, and the ability to genetically tailor the protein provide additional rationale for the exploration of this family of fibrous proteins for biomaterial applications. For example, in designing scaffolds for tissue engineering these properties are particularly relevant and recent results with bone and ligament formation in vitro support the potential role for this biomaterial in future applications. To date, studies with silks to address biomaterial and matrix scaffold needs have focused on silkworm silk. With the diversity of silk-like fibrous proteins from spiders and insects, a range of native or bioengineered variants can be expected for application to a diverse set of clinical needs.
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                Author and article information

                Journal
                ACS Cent Sci
                ACS Cent Sci
                oc
                acscii
                ACS Central Science
                American Chemical Society
                2374-7943
                2374-7951
                13 April 2022
                25 May 2022
                : 8
                : 5
                : 513-526
                Affiliations
                []Weldon School of Biomedical Engineering, Purdue University , West Lafayette, Indiana 47907, United States
                []Department of Mechanical System Engineering, Kumoh National Institute of Technology , 61 Daehak-ro, Gumi-si, Gyeongsangbuk-do 39177, Republic of Korea
                [§ ]Department of Agricultural Biology, National Institute of Agricultural Sciences, Rural Development Administration , Wanju, Jeollabuk-do 55365, Republic of Korea
                []Purdue University Center for Cancer Research , West Lafayette, Indiana 47907, United States
                []Regenstrief Center for Healthcare Engineering , West Lafayette, Indiana 47907, United States
                [# ]Purdue Quantum Science and Engineering Institute , West Lafayette, Indiana 47907, United States
                Author notes
                [* ]Email: tarupa@ 123456korea.kr (S.-W.K.).
                [* ]Email: youngkim@ 123456purdue.edu (Y.L.K.).
                Author information
                https://orcid.org/0000-0001-5008-2356
                https://orcid.org/0000-0003-3796-9643
                Article
                10.1021/acscentsci.1c01233
                9136975
                35647284
                55525e1e-68f5-43f7-a209-4b85f650eb76
                © 2022 The Authors. Published by American Chemical Society

                Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 07 October 2021
                Funding
                Funded by: National Institute of Biomedical Imaging and Bioengineering, doi 10.13039/100000070;
                Award ID: NA
                Funded by: Rural Development Administration, doi 10.13039/501100003627;
                Award ID: PJ015364
                Funded by: Purdue University, doi 10.13039/100006377;
                Award ID: NA
                Funded by: Air Force Office of Scientific Research, doi 10.13039/100000181;
                Award ID: FA2386-17-1-4072
                Categories
                Research Article
                Custom metadata
                oc1c01233
                oc1c01233

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