Advances in Drug Delivery and Theranostics

Abstract

Drug delivery systems (DDS) have been the focus of intense research for several decades. Many approaches and strategies have been employed over the years, further expanding this field. For example, the advancements towards targeted drug delivery (TDD) enabled the use of DDS for diagnostic purposes. In addition, DDS research has provided the foundation for tissue engineering and theranostic systems (therapeutic systems with diagnostic properties). Drug delivery research has yielded many successes over the years with a significant amount of therapeutic and diagnostic products out in the market. Nevertheless, many challenges still remain. Herein, in this special edition, we asked various experts to review recent advancements in their field of expertise and report their latest findings. The special edition is well balanced and is comprised of 60% reviews and 40% research articles. One may find up-to-date reviews on advancements made in biomaterials, noninvasive drug delivery, drug conjugations, biosensors, diagnostics, implantable and ingestible devices, nanomaterials, cancer treatment, and endosome-derived vesicles. Additionally, research articles are provided, describing advanced new designs of microneedles (MNs), approaches to enhance tissue engineering capabilities, biomaterials, and DDS. The global market of protein- and nucleotide- based pharmaceutics accounted for $643 million in 2016, and is anticipated to reach over $8000 million by 2028. However, the use of these therapeutics is hindered by issues of immunogenicity, high molecular weight, fast renal clearance, and enzymatic degradation. For these reasons, to date, monoclonal antibodies (mAbs) are administered only via injection. Considering that, Angsantikul et al. propose the use of ionic liquid and eutectic solvent for the oral delivery of mAbs (article number 2002912). Their system reduced the mucosal viscosity and enhanced the paracellular transport of TNFα antibody in vitro. Additionally, Rondon and colleagues review the latest advancements in polymer chemistry and protein engineering in order to overcome part of these limitations (article number 2101633). Another approach to overcome these limitations is by using antibody-drug conjugates (ADCs). Accordingly, Firer and Luboshits review the recent developments employed in ADCs for the treatment of hematological malignancies (article number 2100032). They focus on the important link between the biology of the ADC and clinical efficacy, highlighting newer developments that strengthen this link to provide long-term clinical benefits. One of the most important purposes of drug delivery is achieving TDD. Dacoba and colleagues provide an overview on the concepts of passive and active targeting while exploring current venues for nanotechnology to solve the problems associated with drug delivery (article number 2009860). TDD is especially important for cancer therapy since killing cancerous cells is quite facile, but killing only cancerous cells is extremely challenging. Fu et al. review the latest strategies employed to overcome the barriers of chimeric antigen receptor T cells therapy in solid tumors (article number 2009489). Brain therapy is another challenging route for drug delivery requiring specific TDD system. To this end, Buaron et al. have developed a novel pectic galactan-based gene therapy approach that targets reactive gliosis via specific carbohydrate interaction between galactan and Gal-3 (article number 2100643). Their biocompatible pectin galatcan-plasmid DNA complexes were selectively transfected to glial cells in cortical lesions. Moreover, Avital et al. report their interesting application for nanosized DDS—foliar delivery of siRNA for treating grapevine leafroll associated virus-3 (GLRaV-3) infection that causes major economic losses (article number 2101003). By exploiting a lipid-modified polyethylenimine carrier, they show that a single dose can knock down GLRaV-3 titer, and multiple doses keeps the viral titer at baseline, which triggers the recovery of the vine and berries. Another important aspect of drug delivery research is the development of noninvasive drug administration routes. Rahamim and Azagury review the origins of biomimetic, bioinspired, and bioengineered noninvasive DDS and achievements made in the last decade (article number 2102033). Additionally, Zhang et al. review advances in DDS that access the ear through the tympanic membrane (article number 2008701). Transdermal drug delivery is one of the most used noninvasive drug delivery routes. An exciting approach for transdermal drug delivery is microneedles (MNs). Puigmal and colleagues propose applying MNs array to treat severe burns that simultaneously sample immune cells in the interstitial fluid to diagnose the response (article number 2100128). Their MNs design enables the local delivery of pharmaceutics—the chemokine CCL22 and the cytokine IL-2—thus increasing local immuno-suppression. They found that the immune cell population in the allograft and MN were similar so they can be harvested from the MN for downstream analysis. Moreover, Li et al. have also proposed an improved MNs design where they use a biphasic dissolvable MN patch with water-insoluble backing in order to tackle insufficient drug delivery with MN (article number 2103359). Their new design enables a drug delivery efficiency of >90% into the skin within 5 min. Biomaterials are the building blocks of drug delivery, diagnostics, and tissue engineering research. Therefore, there is an ever-growing need for novel biomaterials with new functionalities and improved properties. To this end, Arun et al. present an exclusive coverage of biocompatible injectable pasty or liquid polymers without the use of any solvent for drug delivery and regenerative medicine applications (article number 2010284). Moreover, Khait et al. review novel biomaterial-based strategies used to modulate the immune response post ischemic stroke while providing their perspective on the potential clinical translation of these therapies (article number 2010674). Additionally, Redenski et al. developed a new composite tissue made of soft-tissue matrices and decellularized bone for bone defect repair (article number 2008687). The use of their novel tissue composite supported a long-term bone defect repair, as well as muscle defect bridging. These aforementioned applications and additional applications use cell-based therapeutics. The major obstacles of cell-based therapeutics are their low yields (i.e., difficult to scale-up), insufficient drug loading, and inconsistencies. For this reason, Guo et al. have developed a scaled-up and facile magnetic-based extrusion method for preparing endosome-derived vesicles (article number 2008326). An additional application of diagnostics and therapeutics is implantable and ingestible devices. In this special edition, Yang and colleagues provide an up-to-date review on the state-of-the-art of powering technologies for implantable and ingestible electronics—one of the greatest challenges for ingestible devices (article number 2009289). Welch et al. have focused their review on the complex hierarchical nano-structures and nano-materials used in biosensors and diagnostic technologies (article number 2104126). Additionally, they discuss their unique advantages and clinical applications while proposing future directions. In this special edition Nakonechny and Nisnevitch provide an up-to-date review focused on ultrasound applications used to combat infections caused by microorganisms, and to promote the local release of antimicrobial drugs from liposomes and medical implants (article number 2011042). Precise and well-controlled scaffolds are highly desired for tissue engineering and regenerative medicine purposes. For example, Dubay et al. review the recent achievements of single-cell microgels and their potential alternatives, which are used when single cell resolution is needed, for example—modular bio-inks and 3D cellular microenvironments (article number 2009946). Another challenge for implantable devices is a foreign body response (FBR). Kutner et al. review the recent advantageous technologies used to overcome the FBR effect via surface modifications and localized DDS (article number 2010929). One such surface modification is reported by Israeli et al. who developed a general and versatile technology to engineer light-responsive protein-based biomaterials (article number 2011276). These novel biomaterials—consist of azobenzene containing elastin-like polypeptides—are capable of forming self-assembled nanostructures and exhibit a reversible, light-mediated phase transition, with up to a 12 °C difference in the transition temperature. We are certain that this assemblage of reviews and research papers on the use of DDS for therapeutic and diagnostic purposes is of high interest for anyone working in this field. It provides up-to-date reviews on state-of-the-art topics and research papers with promising results to further propel drug delivery research. Understanding what has been done in the past, while learning of new approaches and techniques, is crucial for any scholar who wishes to advance their personal research. Joseph Kost D.Sc. is a University Distinguished Professor, he holds The Abraham and Bessie Zacks Chair in Biomedical Engineering and was the Dean of the Faculty of Engineering Sciences at Ben-Gurion University of the Negev (BGU). He is a member of AIMBE, NAE, CRS, and the Israel Academy of Sciences and Humanities. His research interests are in the fields of biomedical engineering, biomaterials science, controlled drug delivery, gene therapy, and ultrasound. Edith Mathiowitz is a full Professor of Medical Science and Engineering at Brown University, Department of Department of Pathology and Laboratory Medicine. She Is an AIMBE, CRS, and NAI fellow member. She founded and directed the ABC/Biotechnology Graduate Program at Brown. Her interdisciplinary research is focused on developing smart oral bioadhesive delivery systems and novel insights in polymer morphology. Her laboratory serves as an incubator for several start-up companies such as Spherics, Perosphere, and Therapyx. Aharon (Roni) Azagury is an Assistant Professor in the Department of Chemical and Biotechnology Engineering in Ariel University. He received his PhD in chemical engineering from BGU. He is a member of the CRS, ICRS, and NAI societies. His current research focuses on developing novel noninvasive biomimetic and bioinspired drug delivery systems.