Devel. Kinnear C, Moore TL, Rodriguez-Lorenzo L, Rothen-Rutishauser B, Petri-Fink A. Chem Rev. Genet. Most notably amongst these application is Doxil [Barenholz (Chezy), 2012] a liposome encapsulated formulation of doxorubicin for the treatment of cancer, that reduces heart toxicity related to the drug. 2016;13:4452. Expert Opin. (2017). In his previous role he was Head of Preclinical Development at Tavanta Therapeutics. Nanotechnology employs curative agents at the nanoscale level to develop nanomedicines. Google Scholar. A recent trend in the natural product-based drug discovery has been the interest in designing synthetically amenable lead molecules, which mimic their counterparts chemistry [3]. Ouattara B, Simard RE, Holley RA. [177] have synthesized pH responsive quantum dots based on ZnO quantum dots decorated with PEG and hyaluronic acid for become stable in physiological conditions and for targeting specific cells with HA-receptor CD44, respectively. A nanocrystals suspension in a marginal liquid medium is normally alleviated by addition of a surfactant agent known as nano-suspension. This is a biocompatible, negatively charged glycosaminoglycan, and is one of the main constituents of the extracellular matrix [51, 52]. Furthermore, they must be properly folded and often require post-translational modifications (Li et al., 2015) that complicate the synthetic process. Curr Med Chem. Patisiran (Onpattro, Alnylam Pharmaceuticals, FDA approval in August 2018) was the first marketed siRNA-based drug (see Figure 3, Kristen et al., 2018). RNA Nat. Drug Delivery Systems Aptamers have great potential to replace monoclonal antibodies in therapeutic and diagnostic (Damase et al., 2018; Bauer et al., 2019) applications because they can be produced via chemical synthesis, are more cost-effective in manufacturing, simpler to modify, and elicit little immunogenicity. Mater Sci Eng. Further, Malapermal et al. Previously, he held managing positions at diverse international companies such as GSK and Orion Pharma. Available online at: https://www.businesswire.com/news/home/20181001005257/en/InteRNA-Presents-Expanded-Preclinical-Proof-of-concept-Data-Lead (accessed December 26, 2019). 2012;64:30215. [60] prepared perfluorohexane (PFH) nanodroplets stabilized with alginate to drive doxorubicin and then evaluated their sensitivity to ultrasound and imaging as well as their therapeutic properties. in Life Science Engineering, M. Sc. Gene therapy J Nanobiotechnol. Such systems can be easily developed and are capable of promoting the modified release of the active ingredients in the body. doi: 10.1074/jbc.273.32.20556, Russo, E. (2003). mRNA therapy improves metabolic and behavioral abnormalities in a murine model of citrin deficiency. Similarly to BNT162b2, this vaccine encodes stabilized SARS-CoV-2 spike immunogen, and like the BNT mRNA, is delivered intramuscularly as a lipid nanoparticle-encapsulated mRNA (Corbett et al., 2020; Jackson et al., 2020). doi: 10.1038/nbt.3589, Lim, K. R. Q., Maruyama, R., and Yokota, T. (2017). The silicon-lipid hybrid system includes silicon inside, outside, and in between the lipid bilayer. The vaccine consists of six modified mRNA constructs encoding CMV glycoproteins and pentameric complex and is delivered intramuscularly in lipid nanoparticles. 2016;93:5129. Adv. Nat. A minimum viscosity was observed when chitosan nanoparticles were placed in contact with mucin. The targeting of the drugs using different polymeric micelles as established by various mechanism of action including the boosted penetrability and the holding effect stimuli; complexing of a definite aiming ligand molecule to the surface of the micelle; or by combination of the monoclonal antibodies to the micelle corona [146]. 2016;116:282685. Drug Discov. They used their hybrid particles to deliver siRNA and doxorubicin to HeLa cells. 24, 5564. Immunogenicity is a major concern for AAV delivery. Aptamers were first described in 1990 independently by two groups, Ellington and Szostak (1990) and Tuerk and Gold (1990), through systematic evolution of ligand by exponential enrichment (SELEX) technique. Liposomal curcumin formulations have been developed for the treatment of cancer [242, 243]. Besides that, he works as a freelance Lead Auditor with a focus on ISO 13485, ISO 15378, MDSAP (Medical Device Single Audit Program) and Regulation (EU) 2017/745 (MDR) for two Notified Bodies / Auditing Organizations. These nanoparticles degrade into non-toxic products and are safely excreted (Mller et al., 2016; Paris and Vallet-Reg, 2020). Conventional drug strategy relies on the ability of small molecule drugs to target active sites of proteins so as to inhibit or alter their function. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Anything you can do, i can do better: can aptamers replace antibodies in clinical diagnostic applications? Roland Bodmeier is Professor of Pharmaceutical Technology at the College of Pharmacy at the Freie Universitt Berlin, Germany and is co-founder and managing director of Pensatech Pharma GmbH. WebPassword requirements: 6 to 30 characters long; ASCII characters only (characters found on a standard US keyboard); must contain at least 4 different symbols; Gupta U, Sharma S, Khan I, Gothwal A, Sharma AK, Singh Y, Chourasia MK, Kumar V. Enhanced apoptotic and anticancer potential of paclitaxel loaded biodegradable nanoparticles based on chitosan. Coll Surf B. (2014). drug delivery systems The potential for microRNA therapeutics and clinical research. In her current position by Bayer AG her focus is ensuring the regulatory compliance as well as high product quality of medical device and eHealth components of the Pharmaceuticals pipeline and portfolio. The use of large sized materials in drug delivery poses major challenges, including in vivo instability, poor bioavailability, and poor solubility, poor absorption in the body, issues with target-specific delivery, and tonic effectiveness, and probable adverse effects of drugs. Agarwal et al. Jain et al. 6. Examples of natural compounds extracted from higher plants used in nanomedicine aiming different approaches. Mirza AZ, Siddiqui FA. Prior to founding InnoCore in 2004, he worked for Polyganics, a venture capital funded biosurgical start-up company, where he played a key role in developing the company and managed the pre-clinical and clinical development of novel bioresorbable implants and tissue regeneration products in the fields of peripheral nerve repair and general surgery. Acta Biomaterialia. Since 2017 she is working as a (Sr.) formulation scientist at F-Hoffmann-La Roche in R&D Oral dosage forms with a focus on Pediatric formulations, leading and managing development of standard and age-appropriate solid dosage forms of portfolio projects. Efficacy, Safety, and Tolerability of Remlarsen (MRG-201) Following Intradermal Injection in Subjects With a History of Keloids - Full Text View - ClinicalTrials.gov. Epub 2019 May 21. Nature 346, 818822. Wagner-Hattler, L., et al., High Acceptability of an Orally Dispersible Tablet Formulation by Children. Subsequently, they are therapeutically modified ex vivo with mRNA encoding the desired proteins (such as CARs, reprogramming or transdifferentiation factors, telomerase, etc.). 2014;6:139. (2019). doi: 10.1128/MCB.4.10.2072, Tuerk, C., and Gold, L. (1990). Curr Opin Cardiol. (2016). Green Chem Lett Rev. The COVID-19 pandemic has showcased the utility and advantages of RNA technology for vaccination, as out of all COVID-19 vaccines under development, the first two to have received emergency use authorization by the FDA were RNA-based. 10:478. doi: 10.3389/fgene.2019.00478, Harvey, T. J., Anraku, I., Linedale, R., Harrich, D., Mackenzie, J., Suhrbier, A., et al. They were first discovered in C. elegans (Lee et al., 1993). Micellar delivery of dasatinib for the inhibition of pathologic cellular processes of the retinal pigment epithelium. Han-Seung Shin. He assesses biopharmaceutics risk for small-molecule oral programs and large-molecule injectable programs through use of in vitro, in silico, and in vivo methods. Houston Methodist Research Institute is adjacent to the Houston Methodist Hospital, which is ranked by US News and World Report as the No. Opsonins (immunoglobulins and fibronectin, for example) assist RES on recognizing and eliminating liposomes. The efficacy of these natural products has greatly improved through the use of nanocarriers formulated with gold, silver, cadmium sulphide, and titanium dioxide polymeric nanoparticles together with solid lipid nanoparticles, crystal nanoparticles, liposomes, micelles, superparamagnetic iron oxide nanoparticles and dendrimers. Nature 421, 456457. Int Nano Lett. 2015;105:118390. The AAV is a small (25 nm) icosahedral human parvovirus that contains a linear single-stranded DNA (4.7 kb). Alternatively, the AAV vector can be utilized to deliver interference RNA to downregulate the expression of a specific gene. The druggable genome. Sci. Pharmacol. 383, 19201931. Agarwal et al. 2015;33:941. 2, 465478. On the other hand, stimuli-responsive nanocarriers have shown the ability to control the release profile of drugs (as a triggered release) using external factors such as ultrasound [96], heat [97,98,99], magnetism [100, 101], light [102], pH [103], and ionic strength [104], which can improve the targeting and allow greater dosage control (Fig. doi: 10.1146/annurev.pharmtox.010909.105654, Berezhnoy, A., Stewart, C. A., Mcnamara, J. O. II, Thiel, W., Giangrande, P., Trinchieri, G., et al. Available online at: https://www.noxxon.com/index.php?option=com_content&view=article&id=21&Itemid=478 (accessed February 21, 2020). J Nucl Med. PubMed Metabolites. Dr Suha Dadou is currently a Postdoctoral Research Fellow at School of Pharmacy, Queens University Belfast. Drug delivery to the central nervous system Targeting inhibition of Foxp3 by a CD28 2-Fluro oligonucleotide aptamer conjugated to P60-peptide enhances active cancer immunotherapy. Laffleur F, Michalek M. Modified xanthan gum for buccal deliverya promising approach in treating sialorrhea. QDs could also bring benefits in the sustained and/or controlled release of therapeutic molecules. Pharm Res. The combined use of nanoscience along with bioactive natural compounds is very attractive, and growing very rapidly in recent times. J. Lapk L, Lapcik L, De Smedt S, Demeester J, Chabrecek P. Hyaluronan: preparation, structure, properties, and applications. The combination of lipid and polymer permits combination therapy. 2002;54:63151. J Mater Chem B. With this collaboration, we built a seamless transition for academic groups and small companies to go from pre-clinical development and first-in-man clinical trials supported by our hospital-based program, to late-stage clinical trials and commercialization supported by our industry partner VGXI, Inc. Theranostics. Alginate: properties and biomedical applications. McNamara K, Tofail SA. doi: 10.7150/thno.22078, Martinon, F., Krishnan, S., Lenzen, G., Magn, R., Gomard, E., Guillet, J.-G., et al. Asian J Pharm Sci. Pharmacol Res. Each gram of polymer was ligated with 252.5220.54mol of the binder. Patra JK, Baek K-H. Biosynthesis of silver nanoparticles using aqueous extract of silky hairs of corn and investigation of its antibacterial and anticandidal synergistic activity and antioxidant potential. Deliv. This biopolymer presents final carboxyl groups, being classified as anionic mucoadhesive polymer and presents greater mucoadhesive strength when compared with cationic and neutral polymers [59, 118]. Pharmacol. Alexandre earned his Ph.D. in Pharmaceutical Sciences from Paris XI University, France. JKP, LFF, MDPRT, RG, SS, SH and HSS edited the manuscript. Biotechnol Adv. She is currently Senior Technical Transfer Lead at Stein in Switzerland and responsible for the project management of launches and technical transfers of pre-filled syringe and medical device manufacturing.Anja graduated in Chemical and Biological Engineering at the Friedrich Alexander University in Erlangen, Germany and entered the pharmaceutical industry as Global Trainee at Sandoz gaining experience in different sites, countries, and departments. Joey has served as Marketing Director for CDMO division since 2017 and has been involved in pharmaceutical excipient new business development since 2013. Phys Chem Chem Phys. These nanostructures have a strong prospective for hydrophobic drug delivery since their interior core structure permits the assimilation of these kind of drugs resulting in enhancement of stability and bioavailability [141, 142]. The DOI In addition, nanostructures reportedly aid in preventing drugs from being tarnished in the gastrointestinal region and help the delivery of sparingly water-soluble drugs to their target location. 50, 259293. 2015;136:41323. CAS Whereas there is room for further improvement and innovation in each of these areas, the solutions have advanced to the point that RNA Therapeutics are now feasible. Having moved to pharmaceutical industry he developed nanoparticle products with application in cancer, inflammatory diseases autoimmune diseases and other indications. WebAbout Our Coalition. The current review, presents an updated summary of recent advances in the field of nanomedicines and nano based drug delivery systems through comprehensive scrutiny of the discovery and application of nanomaterials in improving both the efficacy of novel and old drugs (e.g., natural products) and selective diagnosis through disease marker molecules. 2011;74:153955. Delivery of therapeutic siRNA to specific tissues is a major challenge. 2013;5:830725. CRISPR (2019c). Drug Delivery Systems Desai, P. R., Marepally, S., Patel, A. R., Voshavar, C., Chaudhuri, A., Singh, M., et al. Vol. In 2019, the FDA Center for Drug Evaluation and Research (CDER) approved 48 new agents, of which 10 were recombinant proteins, peptides or drug-antibody conjugates (Mullard, 2020). Now Approved: GIVLAARITM (givosiran) GIVLAARI. doi: 10.1073/pnas.1118425109, Zheng, P.-P., Kros, J. M., and Li, J. Available online at: https://www.fda.gov/news-events/press-announcements/fda-approval-brings-first-gene-therapy-united-states (accessed August 18, 2020). Epub 2022 Jan 4. [63] prepared a nanoparticulate multifunctional composite system by encapsulating Fe3O4 nanoparticles in dextran nanoparticles conjugated to redox-responsive chlorine 6 (C6) for near infrared (NIR) and magnetic resonance (MR) imaging. Eteplirsen in the treatment of Duchenne muscular dystrophy. As regional technical service manager he is responsible to support R&D and introduce BASF innovations like new excipients and biopharmaceutical ingredients (e.g. Yescarta is another CD19-targeting CAR immunotherapy to treat large B cell lymphoma. This restores the reading frame of the DMD gene and a shortened but functional dystrophin protein is produced (Lim et al., 2017). The particles have high loading capacity for nucleic acids and efficient delivery. Nat. Cancer Res. The authors found that the fluorophore was able to diffuse in the entire bone marrow and label rare populations of cells, such as hematopoietic stem and progenitor cells [172]. New York: Elsevier; 2016. p. 329. Coll Surf B. Although the aforementioned pharmaceutical companies were pioneers in commercialization of mRNA therapeutics, there are many other research groups and biotech start-ups worldwide entering the field. Schematic illustration of intravenous administration of mRNA encapsulated in lipid nanoparticles (LNP) to restore missing/defective protein in hepatic cells (An et al., 2017). Available online at: https://www.jons-online.com/special-issues-and-supplements/2018/2018-third-annual-oncology-guide-to-new-fda-approvals/1829-yescarta-axicabtagene-ciloleucel-second-car-t-cell-therapy-approved-for-patients-with-certain-types-of-large-b-cell-lymphoma (accessed August 18, 2020). He has a Bachelor of Mechanical Engineering degree from Nirma Institute of Technology in India, an MBA from Syracuse University, New York, and he recently completed a post graduate program in cancer biology and therapeutics development from Harvard Medical School. Ding CZ, Li ZB. (2015). Efficient induction of T cells against conserved HIV-1 regions by mosaic vaccines delivered as self-amplifying mRNA. Modernatx. Trends Med Res. If RNA therapeutics are to become the next revolution in medicine, you need better and more sophisticated delivery systems.. doi: 10.1056/NEJMra2035343. Ding Z, Liu P, Hu D, Sheng Z, Yi H, Gao G, Wu Y, Zhang P, Ling S, Cai L. Redox-responsive dextran based theranostic nanoparticles for near-infrared/magnetic resonance imaging and magnetically targeted photodynamic therapy. 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