Abstract:
:In its 33 years, ADDR has published regularly on the po5tential of oral delivery of biologics especially peptides and proteins. In the intervening period, analysis of the preclinical and clinical trial failures of many purported platform technologies has led to reflection on the true status of the field and reigning in of expectations. Oral formulations of semaglutide, octreotide, and salmon calcitonin have completed Phase III trials, with oral semaglutide being approved by the FDA in 2019. The progress made with oral peptide formulations based on traditional permeation enhancers is against a background of low and variable oral bioavailability values of ~1%, leading to a current perception that only potent peptides with a viable cost of synthesis can be realistically considered. Desirable features of candidates should include a large therapeutic index, some stability in the GI tract, a long elimination half-life, and a relatively low clearance rate. Administration in nanoparticle formats have largely disappointed, with few prototypes reaching clinical trials: insufficient particle loading, lack of controlled release, low epithelial particle uptake, and lack of scalable synthesis being the main reasons for discontinuation. Disruptive technologies based on engineered devices promise improvements, but scale-up and toxicology aspects are issues to address. In parallel, medicinal chemists are synthesizing stable hydrophobic macrocyclic candidate peptides of lower molecular weight and with potential for greater oral bioavailability than linear peptides, but perhaps without the same requirement for elaborate drug delivery systems. In summary, while there have been advances in understanding the limitations of peptides for oral delivery, low membrane permeability, metabolism, and high clearance rates continue to hamper progress.
journal_name
Adv Drug Deliv Revjournal_title
Advanced drug delivery reviewsauthors
Brayden DJ,Hill TA,Fairlie DP,Maher S,Mrsny RJdoi
10.1016/j.addr.2020.05.007subject
Has Abstractpub_date
2020-01-01 00:00:00pages
2-36eissn
0169-409Xissn
1872-8294pii
S0169-409X(20)30040-5journal_volume
157pub_type
杂志文章,评审abstract::The threat of bioterrorism worldwide has accelerated the demand for the development of therapies and vaccines against the Category B toxins: staphylococcal enterotoxin B (SEB), epsilon toxin (ETX) produced by Clostridium perfringens types B and D, and ricin, a natural product of the castor bean. The diverse and unique...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2005.01.017
更新日期:2005-06-17 00:00:00
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,...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2020.08.011
更新日期:2020-01-01 00:00:00
abstract::The incorporation of polymer-lipid conjugates, initially using PEG and subsequently other selected flexible, hydrophilic polymers, into lipid bilayers gives rise to sterically stabilized liposomes that exhibit reduced blood clearance and concomitant changes in tissue distribution largely because of reduced, but not el...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章
doi:10.1016/s0169-409x(97)00136-1
更新日期:1998-06-08 00:00:00
abstract::Small interfering RNA (siRNA) that silence genes by the process of RNA interference offers a new therapeutic modality for disease treatment. Polycation-based nanoparticles termed polyplexes have been developed to maximise extracellular and intracellular siRNA delivery, a key requirement for enabling the clinical trans...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2012.07.004
更新日期:2012-12-01 00:00:00
abstract::Magnetic Marker Monitoring offers an alternative to investigate the behavior of solid dosage forms in the organs of the gastrointestinal tract without the need to apply radiation. For Magnetic Marker Monitoring, the dosage form is marked as a permanent magnetic dipole by the incorporation of small amounts of ferromagn...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2005.01.025
更新日期:2005-06-15 00:00:00
abstract::The encouraging pace of discovery and development in the field of regenerative medicine holds tremendous potential for bringing therapies to the clinic that may offer meaningful benefit to patients, particularly in diseases with no or suboptimal therapeutic options. Academic researchers will continue to play a critica...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2016.10.001
更新日期:2017-12-01 00:00:00
abstract::A pharmaceutical formulation is composed of several formulation factors and process variables. Several responses relating to the effectiveness, usefulness, stability, as well as safety must be optimized simultaneously. Consequently, expertise and experience are required to design acceptable pharmaceutical formulations...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/s0169-409x(03)00120-0
更新日期:2003-09-12 00:00:00
abstract::Sensorineural hearing loss (SNHL) is one of the most common diseases, accounting for about 90% of all hearing loss. Leading causes of SNHL include advanced age, ototoxic medications, noise exposure, inherited and autoimmune disorders. Most of SNHL is irreversible and managed with hearing aids or cochlear implants. Alt...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2016.01.004
更新日期:2017-01-01 00:00:00
abstract::Heparin and heparan sulfates are closely related linear anionic polysaccharides, called glycosaminoglycans, which exhibit a number of important biological and pharmacological activities. These polysaccharides, having complex structures and polydispersity, are biosynthesized in the Golgi of animal cells. While heparan ...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2015.11.002
更新日期:2016-02-01 00:00:00
abstract::There is an urgent need for new strategies to combat infectious diseases in developing countries. Many pathogens have evolved to elude immunity and this has limited the utility of current therapies. Additionally, the emergence of co-infections and drug resistant pathogens has increased the need for advanced therapeuti...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2009.11.011
更新日期:2010-03-18 00:00:00
abstract::Safe and effective hemoglobin-based blood substitutes may be advantageous over conventional therapies for certain clinical settings requiring short term blood replacement such as emergency resuscitation and hemodilution in surgery. Many advances have been made in developing these oxygen therapeutics, however safety co...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/s0169-409x(99)00050-2
更新日期:2000-02-28 00:00:00
abstract::A wide range of polymeric scaffolds have been intensively studied for use as implantable and temporal devices in tissue engineering. Biodegradable and biocompatible scaffolds having a highly open porous structure and good mechanical strength are needed to provide an optimal microenvironment for cell proliferation, mig...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2007.03.015
更新日期:2007-05-30 00:00:00
abstract::Recreating the beating heart in the laboratory continues to be a formidable bioengineering challenge. The fundamental feature of the heart is its pumping action, requiring considerable mechanical forces to compress a blood filled chamber with a defined in- and outlet. Ventricular output crucially depends on venous loa...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2015.09.001
更新日期:2016-01-15 00:00:00
abstract::An aging population in the developing world has led to an increase in musculoskeletal diseases such as osteoporosis and bone metastases. Left untreated many bone diseases cause debilitating pain and in the case of cancer, death. Many potential drugs are effective in treating diseases but result in side effects prevent...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2012.01.012
更新日期:2012-09-01 00:00:00
abstract::Nuclear import of macromolecules or particles is a strictly regulated phenomenon that is now understood in some depth at the molecular level. Transport across nuclear membranes is controlled by nuclear pores, with the involvement of cytoplasmic receptors and accessory molecules. Each nuclear pore complex is an assembl...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章
doi:10.1016/s0169-409x(98)00050-7
更新日期:1998-10-05 00:00:00
abstract::In recent years, drug development costs have soared, primarily due to the failure of preclinical animal and cell culture models, which do not directly translate to human physiology. Organ-on-a-chip (OOC) is a burgeoning technology with the potential to revolutionize disease modeling, drug discovery, and toxicology res...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2018.06.001
更新日期:2019-02-01 00:00:00
abstract::Newborn babies can require significant amounts of medication containing excipients intended to improve the drug formulation. Most medicines given to neonates have been developed for adults or older children and contain excipients thought to be safe in these age groups. Many excipients have been used widely in neonates...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章
doi:10.1016/j.addr.2013.11.003
更新日期:2014-06-01 00:00:00
abstract::Arthritis is presently incurable and poorly treatable, but there are good grounds for expecting gene therapy to improve matters considerably. Although local ex vivo delivery of anti-arthritic genes to the synovial lining of joints has shown considerable promise, intraarticular gene delivery may be desirable. Herpes si...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章
doi:10.1016/s0169-409x(97)00021-5
更新日期:1997-08-11 00:00:00
abstract::Amphotericin B colloidal dispersion (ABCD) is a near 1:1 discoidal complex of amphotericin B (AMB) and sodium cholesteryl sulfate (SCS) arranged as a bilayer of SCS interspersed with AMB via noncovalent interactions. The complex is stable in blood and plasma with minimal dissociation. In vitro and in vivo studies show...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/s0169-409x(01)00104-1
更新日期:2001-04-25 00:00:00
abstract::Since conventional liposomes tend to be trapped by the reticuroendothelial systems (RES), their use as drug carriers is limited when the targets are not RES cells. Therefore, many attempts have been made to avoid the RES-trapping of liposomes. Favorable results were obtained by a modification of liposomes with a glucu...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章
doi:10.1016/s0169-409x(99)00040-x
更新日期:1999-11-10 00:00:00
abstract::Topical delivery to the various regions of the skin and underlying tissues, transdermal drug delivery and dermal exposure to environmental chemicals are important areas of research. Mathematical models of epidermal and dermal transport, involving penetration of a solute through various layers of the skin, metabolism i...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2012.04.009
更新日期:2013-02-01 00:00:00
abstract::The assessment of percutaneous permeation of molecules is one of the main steps in the initial design and later in the evaluation of dermal or transdermal drug delivery systems. The literature reports numerous ex vivo, in vitro and in vivo models used to determine drug skin permeation profiles and kinetic parameters, ...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2007.07.004
更新日期:2007-09-30 00:00:00
abstract::Therapeutic cells encapsulated in immunobarrier devices have promise for treatment of a variety of human diseases without immunosuppression. The absence of sufficient oxygen supply to maintain viability and function of encapsulated tissue has been the most critical impediment to progress. Within the framework of oxyge...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2014.02.007
更新日期:2014-04-01 00:00:00
abstract::DNA plasmid-based gene expression systems are being widely investigated for the potential treatment of genetic and acquired disease and for DNA-based vaccination. A number of human clinical trials are in progress using plasmid-based drugs. The regulatory framework that has been applied to biologicals such as recombina...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章
doi:10.1016/s0169-409x(97)00105-1
更新日期:1998-03-02 00:00:00
abstract::Hydrogels have been used primarily in the pharmaceutical field as carriers for delivery of various drugs, peptides and proteins. These systems have included stimuli-responsive gels that exhibit reversible swelling behavior and hence can show modulated release in response to external stimuli such as pH, temperature, io...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/s0169-409x(01)00246-0
更新日期:2002-01-17 00:00:00
abstract::The choroid plexuses (CPs) are leaf-like highly vascular structures laying in the ventricles. The main function of choroid plexuses is the production of the cerebrospinal fluid (CSF). Although CPs have a unique distribution of ion transporters/channels, the mechanism of CSF production is similar to the production of f...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2004.07.005
更新日期:2004-10-14 00:00:00
abstract::Nucleic acids have gained a lot of interest for the treatment of ocular diseases. The first to enter in clinic has been Vitravene an antisense oligonucleotide for the treatment of cytomegalovirus (CMV) infection and more recently, research on aptamers have led to the marketing of anti-vascular endothelial growth facto...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2006.07.020
更新日期:2006-11-15 00:00:00
abstract::Injury to the podocytes is the initiating cause of many renal diseases, leading to proteinuria with possible progression to end-stage renal disease. Podocytes are highly specialized cells, with an important role in maintaining the glomerular filtration barrier and producing growth factors for both mesangial cells and ...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2010.08.012
更新日期:2010-11-30 00:00:00
abstract::Lack of approved pharmaceutical agents and/or pharmacokinetic data in the literature for exotic, wildlife, and zoo species is a major issue for veterinarians. These practitioners must take approved agents (veterinary or human) and extrapolate their use to non-approved species with little or no scientific basis to supp...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/s0169-409x(02)00068-6
更新日期:2002-10-04 00:00:00
abstract::Patients with critical limb ischemia constitute a potential target population for therapeutic angiogenesis. Because the growth of new collateral vessels can be achieved in a time interval of 1 month or less, these patients are suitable candidates for treatment with non-viral vectors intended to yield short-term gene e...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章
doi:10.1016/s0169-409x(97)00115-4
更新日期:1998-03-02 00:00:00