Automation and data-driven design of polymer therapeutics.
Abstract Polymers are uniquely suited for drug delivery and biomaterials applications due to tunable structural parameters such as length, composition, architecture, and valency. To facilitate designs, researchers may explore combinatorial libraries in a high throughput fashion to correlate structure to function. However, traditional polymerization reactions including controlled living radical polymerization (CLRP) and ring-opening polymerization (ROP) require inert reaction conditions and extensive expertise to implement. With the advent of air-tolerance and automation, several polymerization techniques are now c...
Source: Advanced Drug Delivery Reviews - November 23, 2020 Category: Drugs & Pharmacology Authors: Upadhya R, Kosuri S, Tamasi M, Meyer TA, Atta S, Webb MA, Gormley AJ Tags: Adv Drug Deliv Rev Source Type: research

Recent Technological Advancements in Thermometry.
Abstract Thermometry is the key factor for achieving successful thermal therapy. Although invasive thermometry with a probe has been used for more than four decades, this method can only detect the local temperature within the probing volume. Noninvasive temperature imaging using a tomographic technique is ideal for monitoring hot-spot formation in the human body. Among various techniques, such as X-ray computed tomography, microwave tomography, echo sonography, and magnetic resonance (MR) imaging, the proton resonance frequency shift method of MR thermometry is the only method currently available for clinical pra...
Source: Advanced Drug Delivery Reviews - November 17, 2020 Category: Drugs & Pharmacology Authors: Kokuryo D, Kumamoto E, Kuroda K Tags: Adv Drug Deliv Rev Source Type: research

Clinically established biodegradable long acting injectables: An industry perspective.
Abstract Long acting injectable formulations have been developed to sustain the action of drugs in the body over desired periods of time. These delivery platforms have been utilized for both systemic and local drug delivery applications. This review gives an overview of long acting injectable systems that are currently in clinical use. These products are categorized in three different groups: biodegradable polymeric systems, including microparticles and implants; micro and nanocrystal suspensions and oil-based formulations. Furthermore, the applications of these drug delivery platforms for the management of variou...
Source: Advanced Drug Delivery Reviews - November 14, 2020 Category: Drugs & Pharmacology Authors: Nkanga CI, Fisch A, Rad-Malekshahi M, Romic MD, Kittel B, Ullrich T, Wang J, Krause RWM, Adler S, Lammers T, Hennink WE, Ramazani F Tags: Adv Drug Deliv Rev Source Type: research

Peptide and peptide-based inhibitors of SARS-CoV-2 entry.
uml;ller JA Abstract To date, no effective vaccines or therapies are available against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pandemic agent of coronavirus disease 2019 (COVID-19). Due to their safety, efficacy and specificity, peptide inhibitors hold great promise for the treatment of newly emerging viral pathogens. Based on the known structures of viral proteins and their cellular targets, antiviral peptides can be rationally designed and optimized. The resulting peptides may be highly specific for their respective targets and particular viral pathogens or exert broad ant...
Source: Advanced Drug Delivery Reviews - November 12, 2020 Category: Drugs & Pharmacology Authors: Schütz D, Ruiz-Blanco YB, Münch J, Kirchhoff F, Sanchez-Garcia E, Müller JA Tags: Adv Drug Deliv Rev Source Type: research

Delivery technologies for in utero gene therapy.
Abstract Advances in prenatal imaging, molecular diagnostic tools, and genetic screening have unlocked the possibility to treat congenital diseases in utero prior to the onset of clinical symptoms. While fetal surgery and in utero stem cell transplantation can be harnessed to treat specific structural birth defects and congenital hematological disorders, respectively, in utero gene therapy allows for phenotype correction of a wide range of genetic disorders within the womb. However, key challenges to realizing the broad potential of in utero gene therapy are biocompatibility and efficiency of intracellular deliver...
Source: Advanced Drug Delivery Reviews - November 9, 2020 Category: Drugs & Pharmacology Authors: Palanki R, Peranteau WH, Mitchell MJ Tags: Adv Drug Deliv Rev Source Type: research

Transmucosal drug administration as an alternative route in palliative and end-of-life care during the COVID-19 pandemic.
Abstract The Coronavirus disease 2019 (COVID-19) pandemic has led to a surge in need for alternative routes of administration of drugs for end of life and palliative care, particularly in community settings. Transmucosal routes include intranasal, buccal, sublingual and rectal. They are non-invasive routes for systemic drug delivery with the possibility of self-administration, or administration by family caregivers. In addition, their ability to offer rapid onset of action with reduced first-pass metabolism make them suitable for use in palliative and end-of-life care to provide fast relief of symptoms. This is pa...
Source: Advanced Drug Delivery Reviews - October 30, 2020 Category: Drugs & Pharmacology Authors: Lam JKW, Cheung CCK, Chow MYT, Harrop E, Lapwood S, Barclay SIG, Wong ICK Tags: Adv Drug Deliv Rev Source Type: research

Robust and smart polypeptide-based nanomedicines for targeted tumor therapy.
Abstract Nanomedicines based on synthetic polypeptides are among the most versatile and advanced platforms for tumor therapy. Notably, several polypeptide-based nanodrugs are currently under human clinical assessments. The previous (pre)clinical studies clearly show that dynamic stability (i.e. stable in circulation while destabilized in tumor) of nanomedicines plays a vital role in their anti-tumor performance. Various strategies have recently been developed to design dynamically stabilized polypeptide-based nanomedicines by e.g. crosslinking the nanovehicles with acid, reactive oxygen species (ROS), glutathione ...
Source: Advanced Drug Delivery Reviews - October 30, 2020 Category: Drugs & Pharmacology Authors: Deng C, Zhang Q, Guo J, Zhao X, Zhong Z Tags: Adv Drug Deliv Rev Source Type: research

"Old Drugs, New Tricks" - Local controlled drug release systems for treatment of degenerative joint disease.
"Old Drugs, New Tricks" - Local controlled drug release systems for treatment of degenerative joint disease. Adv Drug Deliv Rev. 2020 Oct 26;: Authors: Tryfonidou MA, de Vries G, Hennink WE, Creemers LB Abstract Osteoarthritis (OA) and chronic low back pain (CLBP) caused by intervertebral disc (IVD) degeneration are joint diseases that have become major causes for loss of quality of life worldwide. Despite the unmet need, effective treatments other than invasive, and often ineffective, surgery are lacking. Systemic administration of drugs entails suboptimal local drug exposure in the articul...
Source: Advanced Drug Delivery Reviews - October 26, 2020 Category: Drugs & Pharmacology Authors: Tryfonidou MA, de Vries G, Hennink WE, Creemers LB Tags: Adv Drug Deliv Rev Source Type: research

Recent advances in chemical modifications of guide RNA, mRNA and donor template for CRISPR-mediated genome editing.
Abstract The discovery and applications of clustered regularly interspaced short palindromic repeat (CRISPR) systems have revolutionized our ability to track and manipulate specific nucleic acid sequences in many cell types of various organisms. The robustness and simplicity of these platforms have rapidly extended their applications from basic research to the development of therapeutics. However, many hurdles remain on the path to translation of the CRISPR systems to therapeutic applications: efficient delivery, detectable off-target effects, potential immunogenicity, and others. Chemical modifications provide a ...
Source: Advanced Drug Delivery Reviews - October 26, 2020 Category: Drugs & Pharmacology Authors: Chen Q, Zhang Y, Yin H Tags: Adv Drug Deliv Rev Source Type: research

Synergistic use of biomaterials and licensed therapeutics to manipulate bone remodelling and promote non-union fracture repair.
Abstract Disrupted bone metabolism can lead to delayed fracture healing or non-union, often requiring intervention to correct. Although the current clinical gold standard bone graft implants and commercial bone graft substitutes are effective, they possess inherent drawbacks and are limited in their therapeutic capacity for delayed union and non-union repair. Research into advanced biomaterials and therapeutic biomolecules has shown great potential for driving bone regeneration, although few have achieved commercial success or clinical translation. There are a number of therapeutics, which influence bone remodelli...
Source: Advanced Drug Delivery Reviews - October 26, 2020 Category: Drugs & Pharmacology Authors: Simpson C, Kelly H, Murphy CM Tags: Adv Drug Deliv Rev Source Type: research

Therapeutic potential of polypeptide-based conjugates: Rational design and analytical tools that can boost clinical translation.
nt MJ Abstract The clinical success of polypeptides as polymeric drugs, covered by the umbrella term "polymer therapeutics," combined with related scientific and technological breakthroughs, explain their exponential growth in the development of polypeptide-drug conjugates as therapeutic agents. A deeper understanding of the biology at relevant pathological sites and the critical biological barriers faced, combined with advances regarding controlled polymerization techniques, material bioresponsiveness, analytical methods, and scale up-manufacture processes, have fostered the development of these nature-...
Source: Advanced Drug Delivery Reviews - October 19, 2020 Category: Drugs & Pharmacology Authors: Melnyk T, Đorđević S, Conejos-Sánchez I, Vicent MJ Tags: Adv Drug Deliv Rev Source Type: research

Synthetic peptide hydrogels as 3D scaffolds for tissue engineering.
Abstract The regeneration of tissues and organs poses an immense challenge due to the extreme complexity in the research work involved. Despite the tissue engineering approach being considered as a promising strategy for more than two decades, a key issue impeding its progress is the lack of ideal scaffold materials. Nature-inspired synthetic peptide hydrogels are inherently biocompatible, and its high resemblance to extracellular matrix makes peptide hydrogels suitable 3D scaffold materials. This review covers the important aspects of peptide hydrogels as 3D scaffolds, including mechanical properties, biodegradab...
Source: Advanced Drug Delivery Reviews - October 19, 2020 Category: Drugs & Pharmacology Authors: Ding X, Zhao H, Li Y, Lee AL, Li Z, Fu M, Li C, Yang YY, Yuan P Tags: Adv Drug Deliv Rev Source Type: research

Multifunctional peptides for tumor therapy.
Abstract Controlled nano-systems for drug delivery are designed to deliver therapeutical drugs to desirable sites on demand. Due to the diverse physiological functions of peptides, it is reasonable to introduce peptides into anti-tumor nano-system. The integration of peptides into nanomaterials has complementary advantages, which not only avoids the rapid degradation of peptides in vivo, but also improves the intelligence and functionality of the nano-system. We summarized the functional peptides with targeting and stimulus-responsive properties, and the present review outlined the most relevant and recent develop...
Source: Advanced Drug Delivery Reviews - October 17, 2020 Category: Drugs & Pharmacology Authors: Li K, Liu CJ, Zhang XZ Tags: Adv Drug Deliv Rev Source Type: research

Bioengineered elastin- and silk-biomaterials for drug and gene delivery.
an DL Abstract Advances in medical science have led to diverse new therapeutic modalities, as well as enhanced understanding of the progression of various disease states. These findings facilitate the design and development of more customized and exquisite drug delivery systems that aim to improve therapeutic indices of drugs to treat a variety of conditions. Synthetic polymer-based drug carriers have often been the focus of such research. However, these structures suffer from challenges with heterogeneity of the starting material, limited chemical features, complex functionalization methods, and in some cases a l...
Source: Advanced Drug Delivery Reviews - October 17, 2020 Category: Drugs & Pharmacology Authors: Chambre L, Martín-Moldes Z, Parker RN, Kaplan DL Tags: Adv Drug Deliv Rev Source Type: research

Interaction between high-density lipoproteins and inflammation: Function matters more than concentration!
Abstract High-density lipoprotein (HDL) plays an important role in lipid metabolism and especially contributes to the reverse cholesterol transport pathway. Over recent years it has become clear that the effect of HDL on immune-modulation is not only dependent on HDL concentration but also and perhaps even more so on HDL function. This review will provide a concise general introduction to HDL followed by an overview of post-translational modifications of HDL and a detailed overview of the role of HDL in inflammatory diseases. The clinical potential of HDL and its main apolipoprotein constituent, apoA-I, is also ad...
Source: Advanced Drug Delivery Reviews - October 17, 2020 Category: Drugs & Pharmacology Authors: Nazir S, Jankowski V, Bender G, Zewinger S, Rye KA, van der Vorst EPC Tags: Adv Drug Deliv Rev Source Type: research

Lymphatic immunomodulation using engineered drug delivery systems for cancer immunotherapy.
Abstract Though immunotherapy has revolutionized the treatment of cancer to improve disease outcomes, an array of challenges remain that limit wider clinical success, including low rate of response and immune-related adverse events. Targeting immunomodulatory drugs to therapeutically relevant tissues offers a way to overcome these challenges by potentially enabling enhanced therapeutic efficacy and decreased incidence of side effects. Research highlighting the importance of lymphatic tissues in the response to immunotherapy has increased interest in the application of engineered drug delivery systems (DDSs) to ena...
Source: Advanced Drug Delivery Reviews - October 12, 2020 Category: Drugs & Pharmacology Authors: Manspeaker MP, Thomas SN Tags: Adv Drug Deliv Rev Source Type: research

Lymph-directed immunotherapy - Harnessing endogenous lymphatic distribution pathways for enhanced therapeutic outcomes in cancer.
Abstract The advent of immunotherapy has revolutionised the treatment of some cancers. Harnessing the immune system to improve tumour cell killing is now standard clinical practice and immunotherapy is the first line of defence for many cancers that historically, were difficult to treat. A unifying concept in cancer immunotherapy is the activation of the immune system to mount an attack on malignant cells, allowing the body to recognise, and in some cases, eliminate cancer. However, in spite of a significant proportion of patients that respond well to treatment, there remains a subset who are non-responders and a ...
Source: Advanced Drug Delivery Reviews - October 8, 2020 Category: Drugs & Pharmacology Authors: Feeney OM, Gracia, Brundel DHS, Trevaskis NL, Cao E, Kaminskas LM, Porter CJH Tags: Adv Drug Deliv Rev Source Type: research

Repairing the heart: State-of the art delivery strategies for biological therapeutics.
Abstract Myocardial infarction (MI) is one of the leading causes of mortality worldwide. It is caused by an acute imbalance between oxygen supply and demand in the myocardium, usually caused by an obstruction in the coronary arteries. The conventional therapy is based on the application of (a combination of) anti-thrombotics, reperfusion strategies to open the occluded artery, stents and bypass surgery. However, numerous patients cannot fully recover after these interventions. In this context, new therapeutic methods are explored. Three decades ago, the first biologicals were tested to improve cardiac regeneration...
Source: Advanced Drug Delivery Reviews - October 8, 2020 Category: Drugs & Pharmacology Authors: Yang Q, Fang J, Lei Z, Sluijter JPG, Schiffelers R Tags: Adv Drug Deliv Rev Source Type: research

Designing peptide nanoparticles for efficient brain delivery.
Abstract The targeted delivery of therapeutic compounds to the brain is arguably the most significant open problem in drug delivery today. Nanoparticles (NPs) based on peptides and designed using the emerging principles of molecular engineering show enormous promise in overcoming many of the barriers to brain delivery faced by NPs made of more traditional materials. However, shortcomings in our understanding of peptide self-assembly and blood-brain barrier (BBB) transport mechanisms pose significant obstacles to progress in this area. In this review, we discuss recent work in engineering peptide nanocarriers for t...
Source: Advanced Drug Delivery Reviews - October 5, 2020 Category: Drugs & Pharmacology Authors: Duro-Castano A, Leite DM, Forth J, Deng Y, Matias D, Jesus CN, Battaglia G Tags: Adv Drug Deliv Rev Source Type: research

Diseases and conditions that impact maternal and fetal health and the potential for nanomedicine therapies.
Abstract Maternal mortality rates in the United States have steadily increased since 1987 to the current rate of over 16 deaths per 100,000 live births. Whereas most of these deaths are related to an underlying condition, such as cardiovascular disease, many pregnant women die from diseases that emerge as a consequence of pregnancy. Both pre-existing and emergent diseases and conditions are difficult to treat in pregnant women because of the potential harmful effects of the treatment on the developing fetus. Often the health of the woman and the health of the baby are at odds and must be weighed against each other...
Source: Advanced Drug Delivery Reviews - September 27, 2020 Category: Drugs & Pharmacology Authors: Nelson KM, Irvin-Choy N, Hoffman MK, Gleghorn JP, Day ES Tags: Adv Drug Deliv Rev Source Type: research

Engineered tissues and strategies to overcome challenges in drug development.
Abstract Current preclinical studies in drug development utilize high-throughput in vitro screens to identify lead drug candidates, followed by both in vitro and in vivo models to predict lead candidates' pharmacokinetic and pharmacodynamic properties. The goal of these studies is to reduce the number of lead drug candidates down to the most likely to succeed in later human clinical trials. However, only 1 in 10 drug candidates that emerge from preclinical studies will succeed and become an approved therapeutic. Lack of efficacy or undetected toxicity represents roughly 75% of the causes for these failures, despit...
Source: Advanced Drug Delivery Reviews - September 24, 2020 Category: Drugs & Pharmacology Authors: Khalil AS, Jaenisch R, Mooney DJ Tags: Adv Drug Deliv Rev Source Type: research

Power of mitochondrial drug delivery systems to produce innovative nanomedicines.
Abstract Mitochondria carry out various essential functions including ATP production, the regulation of apoptosis and possess their own genome (mtDNA). Delivering target molecules to this organelle, it would make it possible to control the functions of cells and living organisms and would allow us to develop a better understanding of life. Given the fact that mitochondrial dysfunction has been implicated in a variety of human disorders, delivering therapeutic molecules to mitochondria for the treatment of these diseases is an important issue. To date, several mitochondrial drug delivery system (DDS) developments h...
Source: Advanced Drug Delivery Reviews - September 24, 2020 Category: Drugs & Pharmacology Authors: Yamada Y, Satrialdi, Hibino M, Sasaki D, Abe J, Harashima H Tags: Adv Drug Deliv Rev Source Type: research

Electroactive material-based biosensors for detection and drug delivery.
Abstract Electroactive materials are employed at the interface of biology and electronics due to their advantageous intrinsic properties as soft organic electronics. We examine the most recent literature of electroactive material-based biosensors and their emerging role as theranostic devices for the delivery of therapeutic agents. We consider electroactive materials through the lens of smart drug delivery systems as materials that enable the release of therapeutic cargo in response to specific physiological and external stimuli and discuss the way these mechanisms are integrated into medical devices with examples...
Source: Advanced Drug Delivery Reviews - September 24, 2020 Category: Drugs & Pharmacology Authors: Olvera D, Monaghan MG Tags: Adv Drug Deliv Rev Source Type: research

Polymeric micelles for the delivery of poorly soluble drugs: From nanoformulation to clinical approval.
Abstract Over the last three decades, polymeric micelles have emerged as a highly promising drug delivery platform for therapeutic compounds. Particularly, poorly soluble small molecules with high potency and significant toxicity were encapsulated in polymeric micelles. Polymeric micelles have shown improved pharmacokinetic profiles in preclinical animal models and enhanced efficacy with a superior safety profile for therapeutic drugs. Several polymeric micelle formulations have reached the clinical stage and are either in clinical trials or are approved for human use. This furthers interest in this field and unde...
Source: Advanced Drug Delivery Reviews - September 23, 2020 Category: Drugs & Pharmacology Authors: Hwang D, Ramsey JD, Kabanov AV Tags: Adv Drug Deliv Rev Source Type: research

Building three-dimensional lung models for studying pharmacokinetics of inhaled drugs.
Abstract Drug development is a critical step in the development pipeline of pharmaceutical industry, commonly performed in traditional cell culture and animal models. Though, those models hold critical gapsin the prediction and the translation of human pharmacokinetic (PK) and pharmacodynamics (PD) parameters. The advances in tissue engineering have allowed the combination of cell biology with microengineering techniques, offering alternatives to conventional preclinical models. Organ-on-a-chips and three-dimensional (3D) bioprinting models present the potentialityof simulating the physiological and pathological m...
Source: Advanced Drug Delivery Reviews - September 20, 2020 Category: Drugs & Pharmacology Authors: Barros AS, Costa A, Sarmento B Tags: Adv Drug Deliv Rev Source Type: research

Role of CFD based in silico modelling in establishing an in vitro-in vivo correlation of aerosol deposition in the respiratory tract.
Abstract Effective evaluation and prediction of aerosol transport deposition in the human respiratory tracts are critical to aerosol drug delivery and evaluation of inhalation products. Establishment of an in vitro-in vivo correlation (IVIVC) requires the understanding of flow and aerosol behaviour and underlying mechanisms at the microscopic scale. The achievement of the aim can be facilitated via computational fluid dynamics (CFD) based in silico modelling which treats the aerosol delivery as a two-phase flow. CFD modelling research, in particular copuling with discrete phase model (DPM) and discrete element met...
Source: Advanced Drug Delivery Reviews - September 20, 2020 Category: Drugs & Pharmacology Authors: Huang F, Zhu Q, Zhou X, Gou D, Yu J, Li R, Tong Z, Yang R Tags: Adv Drug Deliv Rev Source Type: research

Fibronectin in development and wound healing.
Abstract Fibronectin structure and composition regulate contextual cell signaling. Recent advances have been made in understanding fibronectin and its role in tissue organization and repair. This review outlines fibronectin splice variants and their functions, evaluates potential therapeutic strategies targeting or utilizing fibronectin, and concludes by discussing potential future directions to modulate fibronectin function in development and wound healing. PMID: 32961203 [PubMed - as supplied by publisher] (Source: Advanced Drug Delivery Reviews)
Source: Advanced Drug Delivery Reviews - September 18, 2020 Category: Drugs & Pharmacology Authors: Patten J, Wang K Tags: Adv Drug Deliv Rev Source Type: research

Exploiting the placenta for nanoparticle-mediated drug delivery during pregnancy.
Abstract A major challenge to treating diseases during pregnancy is that small molecule therapeutics are transported through the placenta, and incur toxicities to the developing fetus. The placenta is solely responsible for providing nutrients, removing waste, and protecting the fetus from toxic substances in maternal circulation. Thus, the placenta acts as a biological barrier between the mother and fetus that can be exploited for drug delivery. Nanoparticle technologies provide the opportunity for safe drug delivery during pregnancy by controlling how therapeutics interact with the placenta. In this Review, we p...
Source: Advanced Drug Delivery Reviews - September 17, 2020 Category: Drugs & Pharmacology Authors: Figueroa-Espada CG, Mitchell MJ, Riley RS Tags: Adv Drug Deliv Rev Source Type: research

Advances on erythrocyte-mimicking nanovehicles to overcome barriers in biological microenvironments.
Abstract Although nanocarriers offer many advantages as drug delivery systems, their poor stability in circulation, premature drug release and nonspecific uptake in non-target organs have prompted biomimetic approaches using natural cell membranes to camouflage nanovehicles. Among them, erythrocytes, representing the most abundant blood circulating cells, have been extensively investigated for biomimetic coating on artificial nanocarriers due to their upgraded biocompatibility, biodegradability, non-immunogenicity and long-term blood circulation. Due to the cell surface mimetic properties combined with customized ...
Source: Advanced Drug Delivery Reviews - September 14, 2020 Category: Drugs & Pharmacology Authors: Castro F, Martins C, Silveira MJ, Moura RP, Pereira CL, Sarmento B Tags: Adv Drug Deliv Rev Source Type: research

Non-viral strategies for delivering genome editing enzymes.
thy N Abstract Genome-editing tools such as Cre recombinase (Cre), zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and most recently the clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein system have revolutionized biomedical research, agriculture, microbial engineering, and therapeutic development. Direct delivery of genome editing enzymes, as opposed to their corresponding DNA and mRNA precursors, is advantageous since they do not require transcription and/or translation. In addition, prolonged overexpression is a problem when delivering v...
Source: Advanced Drug Delivery Reviews - September 11, 2020 Category: Drugs & Pharmacology Authors: Li J, Røise JJ, He M, Das R, Murthy N Tags: Adv Drug Deliv Rev Source Type: research

When liposomes met antibodies: Drug delivery and beyond.
Abstract Drug encapsulated liposomes and monoclonal antibodies (Mabs) are two distinctively different classes of therapeutics, but both aim to become the ultimate "magic bullet". While PEGylated liposomes rely on the enhanced permeability and retention (EPR) effect for accumulation in solid tumor tissues, Mabs are designed to bind tightly to specific surface antigens on target cells to exert effector functions. Immunoliposome (IL) refers to the structural combination of liposomes and antibodies, whereas the antibodies are usually decorated on the liposome surface. ILs can therefore take advantage of inte...
Source: Advanced Drug Delivery Reviews - September 10, 2020 Category: Drugs & Pharmacology Authors: Di J, Xie F, Xu Y Tags: Adv Drug Deliv Rev Source Type: research

In vitro - in vivo correlation of intranasal drug deposition.
Abstract In vitro - in vivo correlation (IVIVC) allows prediction of in vivo drug deposition from a nasally inhaled drug based on in vitro drug measurements. In vitro measurements include physical particle characterization and, more recently, deposition studies using anatomical models. Currently, there is a lack of IVIVC for deposition measurements in anatomical models, especially for deposition patterns in various nasal cavity regions. Therefore, improvement of in vitro and in vivo measurement methods and knowledge about nasal deposition mechanisms should help IVIVC in the future. PMID: 32918968 [PubMed - as...
Source: Advanced Drug Delivery Reviews - September 8, 2020 Category: Drugs & Pharmacology Authors: Le Guellec S, Ehrmann S, Vecellio L Tags: Adv Drug Deliv Rev Source Type: research

Imaging technology of the lymphatic system.
Abstract The lymphatic system plays critical roles in tissue fluid homeostasis and immunity and has been implicated in the development of many different pathologies, ranging from lymphedema, the spread of cancer to chronic inflammation. In this review, we first summarize the state-of-the-art of lymphatic imaging in the clinic and the advantages and disadvantages of these existing techniques. We then detail recent progress on imaging technology, including advancements in tracer design and injection methods, that have allowed visualization of lymphatic vessels with excellent spatial and temporal resolution in precli...
Source: Advanced Drug Delivery Reviews - September 2, 2020 Category: Drugs & Pharmacology Authors: Polomska A, Proulx ST Tags: Adv Drug Deliv Rev Source Type: research

Exploiting Nanoscale Cooperativity for precision medicine.
Abstract Precise spatiotemporal control of molecular transport is vital to functional physiological systems. Nature evolved to apply macromolecular cooperativity to achieve precision over systemic delivery of important molecules. In drug delivery, conventional nanocarriers employ inert materials and rely on passive accumulation for tissue targeting and diffusion for drug release. Early clinical studies show these nanodrugs have not delivered the anticipated impact on therapy. Inspired by nature, we propose a design principle that incorporates nanoscale cooperativity and phase transition to sense and amplify physio...
Source: Advanced Drug Delivery Reviews - August 30, 2020 Category: Drugs & Pharmacology Authors: Wilhelm J, Wang Z, Sumer BD, Gao J Tags: Adv Drug Deliv Rev Source Type: research

Recent trends in protein and peptide-based biomaterials for advanced drug delivery.
PMID: 32871201 [PubMed - as supplied by publisher] (Source: Advanced Drug Delivery Reviews)
Source: Advanced Drug Delivery Reviews - August 28, 2020 Category: Drugs & Pharmacology Authors: Varanko A, Saha S, Chilkoti A Tags: Adv Drug Deliv Rev Source Type: research

Targeting and therapeutic peptide-based strategies for polycystic kidney disease.
Abstract Polycystic kidney disease (PKD) is characterized by progressive cyst growth and is a leading cause of renal failure worldwide. Currently, there are limited therapeutic options available to PKD patients, and only one drug, tolvaptan, has been FDA-approved to slow cyst progression. Similar to other small molecule drugs, however, tolvaptan is costly, only moderately effective, and causes adverse events leading to high patient dropout rates. Peptides may mitigate many drawbacks of small molecule drugs, as they can be highly tissue-specific, biocompatible, and economically scaled-up. Peptides can function as t...
Source: Advanced Drug Delivery Reviews - August 27, 2020 Category: Drugs & Pharmacology Authors: Wang J, Tripathy N, Chung EJ Tags: Adv Drug Deliv Rev Source Type: research

Microphysiological Systems of the Placental Barrier.
Abstract Methods to evaluate maternal-fetal transport across the placental barrier have generally involved clinical observations after-the-fact, ex vivo perfused placenta studies, or in vitro Transwell assays. Given the ethical and technical limitations in these approaches, and the drive to understand fetal development through the lens of transport-induced injury, such as with the example of thalidomide and Zika Virus, efforts to develop novel approaches to study these phenomena have expanded in recent years. Notably, within the past 10 years, placental barrier models have been developed using hydrogel, bioreact...
Source: Advanced Drug Delivery Reviews - August 24, 2020 Category: Drugs & Pharmacology Authors: Arumugasaamy N, Rock KD, Kuo CY, Bale TL, Fisher JP Tags: Adv Drug Deliv Rev Source Type: research

Current strategies and opportunities to manufacture cells for modeling human lungs.
Abstract Chronic lung diseases remain major healthcare burdens, for which the only curative treatment is lung transplantation. In vitro human models are promising platforms for identifying and testing novel compounds to potentially decrease this burden. Directed differentiation of pluripotent stem cells is an important strategy to generate lung cells to create such models. Current lung directed differentiation protocols are limited as they do not 1) recapitulate the diversity of respiratory epithelium, 2) generate consistent or sufficient cell numbers for drug discovery platforms, and 3) establish the histologic t...
Source: Advanced Drug Delivery Reviews - August 20, 2020 Category: Drugs & Pharmacology Authors: Varma R, Soleas JP, Waddell TK, Karoubi G, McGuigan AP Tags: Adv Drug Deliv Rev Source Type: research

Exosomes and GPI-anchored proteins: Judicious pairs for investigating biomarkers from body fluids.
Abstract Exosomes are 50-100 nm membranous vesicles actively released by cells which can be indicative of a diseased cell status. They contain various kinds of molecule - proteins, mRNA, miRNA, lipids - that are actively being studied as potential biomarkers. Hereafter I put forward several arguments in favor of the potential use of glycosylphosphatidylinositol-anchored proteins (GPI-APs) as biomarkers especially of cancerous diseases. I will briefly update readers on the exosome field and review various features of GPI-APs, before further discussing the advantages of this class of proteins as potential exosomal...
Source: Advanced Drug Delivery Reviews - August 19, 2020 Category: Drugs & Pharmacology Authors: Vidal M Tags: Adv Drug Deliv Rev Source Type: research

Multimodal stratified imaging of nanovaccines in lymph nodes for improving cancer immunotherapy.
Abstract Vaccines hold enormous potential in cancer immunotherapy by stimulating the body's immune response; unfortunately, the clinical response rates of cancer vaccines are less than 30%. Nanovaccines show the potential to enhance the treatment efficacy of conventional vaccines due to their unique properties, such as efficient co-delivery of cocktail to the secondary lymphatic system, high tumor accumulation and penetration, and customizable delivery of antigens and adjuvants. Meanwhile, the non-invasive visualization of vaccines after their delivery can yield information about in vivo distribution and performan...
Source: Advanced Drug Delivery Reviews - August 18, 2020 Category: Drugs & Pharmacology Authors: Tian R, Ke C, Rao L, Lau J, Chen X Tags: Adv Drug Deliv Rev Source Type: research

Targeting cell plasticity for regeneration: from in vitro to in vivo reprogramming.
Abstract The discovery of induced pluripotent stem cells (iPSCs), reprogrammed to pluripotency from somatic cells, has transformed the landscape of regenerative medicine, disease modelling and drug discovery pipelines. Since the first generation of iPSCs in 2006, there has been enormous effort to develop new methods that increase reprogramming efficiency, and obviate the need for viral vectors. In parallel to this, the promise of in vivo reprogramming to convert cells into a desired cell type to repair damage in the body, constitutes a new paradigm in approaches for tissue regeneration. This review article explore...
Source: Advanced Drug Delivery Reviews - August 17, 2020 Category: Drugs & Pharmacology Authors: Romanazzo S, Lin K, Srivastava P, Kilian K Tags: Adv Drug Deliv Rev Source Type: research

Lipoprotein-based drug delivery.
Abstract Lipoproteins (LPs) are circulating heterogeneous nanoparticles produced by the liver and intestines. LPs play a major role in the transport of dietary and endogenous lipids to target cells through cell membrane receptors or cell surface-bound lipoprotein lipase. The stability, biocompatibility, and selective transport of LPs make them promising delivery vehicles for various therapeutic and imaging agents. This review discusses isolation, manufacturing, and drug loading techniques used for LP-based drug delivery, as well as recent applications for diagnosis and treatment of cancer, atherosclerosis, and oth...
Source: Advanced Drug Delivery Reviews - August 9, 2020 Category: Drugs & Pharmacology Authors: Busatto S, Walker SA, Grayson W, Pham A, Tian M, Nesto N, Barklund J, Wolfram J Tags: Adv Drug Deliv Rev Source Type: research

Lipid in the midst of metabolic remodeling - Therapeutic implications for the failing heart.
Abstract A healthy heart relies on an intact cardiac lipid metabolism. Fatty acids represent the major source for ATP production in the heart. Not less importantly, lipids are directly involved in critical processes such as cell growth, proliferation, and cell death by functioning as building blocks or signaling molecules. In the development of heart failure, perturbations in fatty acid utilization impair cardiac energetics. Furthermore, they may affect glucose and amino acid metabolism and induce the synthesis of several lipid intermediates, whose biological functions are still poorly understood. This work outlin...
Source: Advanced Drug Delivery Reviews - August 9, 2020 Category: Drugs & Pharmacology Authors: Nguyen TD, Schulze PC Tags: Adv Drug Deliv Rev Source Type: research

Stromal regulation of tufmor-associated lymphatics.
Abstract Recent advances have identified a growing array of roles played by lymphatics in the tumor microenvironment, from providing a route of metastasis to immune modulation. The tumor microenvironment represents an exceptionally complex, dynamic niche comprised of a diverse mixture of cancer cells and normal host cells termed the stroma. This review discusses our current understanding of stromal elements and how they regulate lymphatic growth and functional properties in the tumor context. PMID: 32783989 [PubMed - as supplied by publisher] (Source: Advanced Drug Delivery Reviews)
Source: Advanced Drug Delivery Reviews - August 8, 2020 Category: Drugs & Pharmacology Authors: Munir H, Mazzaglia C, Shields JD Tags: Adv Drug Deliv Rev Source Type: research

An RNAi therapeutic, DFP-10825, for intraperitoneal and intrapleural malignant cancers.
Abstract RNA interference (RNAi), a potent post-transcriptional gene-silencing action, has received considerable attentions as a novel therapeutic tool to treat intractable cancers. In recent days, we have developed a novel RNAi-based therapeutic formulation, DFP-10825, for the treatment of intractable advanced cancers developed in coelomic cavities. DFP-10825 was composed of chemically synthesized short hairpin RNA (shRNA) against thymidylate synthase (TS), a key enzyme for cancer proliferation, and cationic liposomes, and achieved high therapeutic effect on the mouse models of peritoneally disseminated gastric a...
Source: Advanced Drug Delivery Reviews - August 7, 2020 Category: Drugs & Pharmacology Authors: Ando H, Ishida T Tags: Adv Drug Deliv Rev Source Type: research

Development of Promitil ®, a lipidic prodrug of mitomycin c in PEGylated liposomes: From bench to bedside.
Development of Promitil®, a lipidic prodrug of mitomycin c in PEGylated liposomes: From bench to bedside. Adv Drug Deliv Rev. 2020 Aug 07;: Authors: Gabizon A, Shmeeda H, Tahover E, Kornev G, Patil Y, Amitay Y, Ohana P, Sapir E, Zalipsky S Abstract Several liposome products have been approved for the treatment of cancer. In all of them, the active agents are encapsulated in the liposome water phase passively or by transmembrane ion gradients. An alternative approach in liposomal drug delivery consists of chemically modifying drugs to form lipophilic prodrugs with strong association to the liposoma...
Source: Advanced Drug Delivery Reviews - August 6, 2020 Category: Drugs & Pharmacology Authors: Gabizon A, Shmeeda H, Tahover E, Kornev G, Patil Y, Amitay Y, Ohana P, Sapir E, Zalipsky S Tags: Adv Drug Deliv Rev Source Type: research

Recent advances in siRNA delivery mediated by lipid-based nanoparticles.
Abstract Small interfering RNA (siRNA) has been expected to be a unique pharmaceutic for the treatment of broad-spectrum intractable diseases. However, its unfavorable properties such as easy degradation in the blood and negative-charge density are still a formidable barrier for clinical use. For disruption of this barrier, siRNA delivery technology has been significantly advanced in the past two decades. The approval of Patisiran (ONPATTRO™) for the treatment of transthyretin-mediated amyloidosis, the first approved siRNA drug, is a most important milestone. Since lipid-based nanoparticles (LNPs) are used i...
Source: Advanced Drug Delivery Reviews - August 4, 2020 Category: Drugs & Pharmacology Authors: Yonezawa S, Koide H, Asai T Tags: Adv Drug Deliv Rev Source Type: research

In vitro, ex vivo and in vivo methods of lung absorption for inhaled drugs.
Abstract The assessment and prediction of lung absorption and disposition are an increasingly essential preclinical task for successful discovery and product development of inhaled drugs for both local and systemic delivery. Hence, in vitro, ex vivo and in vivo preclinical methods of lung absorption continue to evolve with several technical, methodological and analytical refinements. As in vitro lung epithelial cell monolayer models, the air-liquid interface (ALI)-cultured Calu-3 cells have most frequently been used, but the NCI-H441 and hAELVi cells have now been proposed as the first immortalized human alveolar ...
Source: Advanced Drug Delivery Reviews - August 3, 2020 Category: Drugs & Pharmacology Authors: Sakagami M Tags: Adv Drug Deliv Rev Source Type: research

Application of advances in endocytosis and membrane trafficking to drug delivery.
Abstract Multidisciplinary research efforts in the field of drug delivery have led to the development of a variety of drug delivery systems (DDS) designed for site-specific delivery of diagnostic and therapeutic agents. Since efficient uptake of drug carriers into target cells is central to effective drug delivery, a comprehensive understanding of the biological pathways for cellular internalization of DDS can facilitate the development of DDS capable of precise tissue targeting and enhanced therapeutic outcomes. Diverse methods have been applied to study the internalization mechanisms responsible for endocytotic ...
Source: Advanced Drug Delivery Reviews - August 2, 2020 Category: Drugs & Pharmacology Authors: Ju Y, Guo H, Edman M, Hamm-Alvarez SF Tags: Adv Drug Deliv Rev Source Type: research

Cell and tissue engineering in lymph nodes for cancer immunotherapy.
Abstract In cancer, lymph nodes (LNs) coordinate tumor antigen presentation necessary for effective antitumor immunity, both at the levels of local cellular interactions and tissue-level organization. In this review, we examine how LNs may be engineered to improve the therapeutic outcomes of cancer immunotherapy. At the cellular scale, targeting the LNs impacts the potency of cancer vaccines, immune checkpoint blockade, and adoptive cell transfer. On a tissue level, macro-scale biomaterials mimicking LN features can function as immune niches for cell reprogramming or delivery in vivo, or be utilized in vitro to en...
Source: Advanced Drug Delivery Reviews - July 31, 2020 Category: Drugs & Pharmacology Authors: Najibi AJ, Mooney DJ Tags: Adv Drug Deliv Rev Source Type: research