Abstract:
:With inhalational delivery the alveolar epithelium appears to be the appropriate lung surface to target for the systemic delivery of macromolecules, such as therapeutic proteins. The existence of a high numerical density of smooth-coated or non-coated plasma membrane vesicles or invaginations within the alveolar epithelial type I cell has long been recognised. The putative function of these vesicles in macromolecule transport remains the focus of research in both pulmonary physiology and pharmaceutical science disciplines. These vesicles, or subpopulations thereof, have been shown to biochemically possess caveolin, a marker protein for caveolae. This review considers the morphometric and biochemical studies that have progressed the characterisation of the vesicle populations within alveolar type I epithelium. Parallel research findings from the endothelial literature have been considered to contrast the state of progress of caveolae research in alveolar epithelium. Speculation is made on a model of caveolae vesicle-mediated transport that may satisfy some of the pulmonary pharmacokinetic data that has been generated for macromolecule absorption. The putative transport function of caveolae within alveolar epithelium is reviewed with respect to in-situ tracer studies conducted within the alveolar airspace. Finally, the functional characterisation of in-vitro alveolar epithelial cell cultures is considered with respect to the role of caveolae in macromolecule transport. A potentially significant role for alveolar caveolae in mediating the alveolar airspace to blood transport of macromolecules cannot be dismissed. Considerable research is required, however, to address this issue in a quantitative manner. A better understanding of the membrane dynamics of caveolae in alveolar epithelium will help resolve the function of these vesicular compartments and may lead to the development of more specific drug targeting approaches for promoting pulmonary drug delivery.
journal_name
Adv Drug Deliv Revjournal_title
Advanced drug delivery reviewsauthors
Gumbleton Mdoi
10.1016/s0169-409x(01)00142-9subject
Has Abstractpub_date
2001-07-28 00:00:00pages
281-300issue
3eissn
0169-409Xissn
1872-8294pii
S0169409X01001429journal_volume
49pub_type
杂志文章,评审abstract::Many drug molecules possess inadequate physical-chemical characteristics that prevent to surpass the viscous mucus layer present in the surface of mucosal tissues. Due to mucus protective role and its fast turnover, these drug molecules end up being removed from the body before being absorbed and, thus, before exertin...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2017.09.020
更新日期:2018-01-15 00:00:00
abstract::A mechanistic hypothesis is presented for how water-soluble guanidinium-rich transporters attached to small cargoes (MW ca. <3000) can migrate across the non-polar lipid membrane of a cell and enter the cytosol. Positively charged and water-soluble, arginine oligomers can associate with negatively charged, bidentate h...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2004.10.003
更新日期:2005-02-28 00:00:00
abstract::Despite advances in medicine and biomedical sciences, cancer still remains a major health issue. Complex interactions between tumors and their microenvironment contribute to tumor initiation and progression and also contribute to the development of drug resistant tumor cell populations. The complexity and heterogeneit...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2014.07.002
更新日期:2014-12-15 00:00:00
abstract::Oral delivery is the most common method for drug administration. However, poor solubility, stability, and bioavailability of many drugs make achieving therapeutic levels via the gastrointestinal (GI) tract challenging. Drug delivery must overcome numerous hurdles, including the acidic gastric environment and the conti...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2011.12.009
更新日期:2012-05-01 00:00:00
abstract::Type 1 diabetes is an autoimmune disease marked by the destruction of insulin-producing beta cells in the pancreatic islets. Strategies to delay onset or prevent the autoimmune recognition of beta cell antigens or T cell-mediated killing of beta cells have mainly focused on systemic immunomodulation and antigen-specif...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2017.06.007
更新日期:2017-05-15 00:00:00
abstract::The biological clock of mammals is under the control of external factors, social life and the environment, and of internal genetic factors. When the biological clock of an individual is no longer in phase with its environment, either because there is no longer any harmony (desynchronization) between the two systems (s...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2010.06.005
更新日期:2010-07-31 00:00:00
abstract::Whereas in vivo studies represent the most crucial test for any nasal drug application or formulation, mechanistic aspects of nasal absorption may be more clearly approached by well defined and controlled in vitro studies. In this review the progress of nasal in vitro models to investigate drug permeation and metaboli...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章
doi:10.1016/s0169-409x(97)00061-6
更新日期:1998-01-05 00:00:00
abstract::Mitochondria represent both the main source and target of reactive oxygen and nitrogen species (RONS). In view of the large energy expenditure made by neurons during neurotransmission, an intact mitochondrial function is of paramount importance for the correct function of the brain. Accordingly, the search of therapeu...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2009.05.009
更新日期:2009-11-30 00:00:00
abstract::Non-communicable diseases including cancer, cardiovascular disease, diabetes, and neuropathy are chronic in nature. Treatment of these diseases with traditional delivery systems is limited due to lack of site-specificity, non-spatiotemporal release and insufficient doses. Numerous responsive delivery systems which res...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2018.02.008
更新日期:2018-04-01 00:00:00
abstract::Clinical trials are crucial to determining the human safety and efficacy of new therapeutic innovations. Extraordinary amounts of human experiential data are generated over the course of any clinical trial, however, much of these data is never made publicly accessible. Improved, reliable data sharing is essential to i...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2018.01.017
更新日期:2018-01-01 00:00:00
abstract::Tendon injuries represent a significant clinical burden on healthcare systems worldwide. As the human population ages and the life expectancy increases, tendon injuries will become more prevalent, especially among young individuals with long life ahead of them. Advancements in engineering, chemistry and biology have m...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2014.11.022
更新日期:2015-04-01 00:00:00
abstract::This review presents a summary of the various types of cellular therapy used to treat spinal cord injury. The inhibitory environment and loss of axonal connections after spinal cord injury pose many obstacles to regenerating the lost tissue. Cellular therapy provides a means of restoring the cells lost to the injury a...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2007.08.028
更新日期:2008-01-14 00:00:00
abstract::Immunotherapy has been widely explored for applications to both augment and suppress intrinsic host immunity. Clinical achievements have seen a number of immunotherapeutic drugs displace established strategies like chemotherapy in treating immune-associated diseases. However, single drug approaches modulating an indiv...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2017.05.013
更新日期:2017-05-15 00:00:00
abstract::The interaction of biological cells with artificial biomaterials is one of the most important issues in tissue engineering and regenerative medicine. The interaction is strongly governed by physical and chemical properties of the materials and displayed with differentiated cellular behaviors, including cell self-renew...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2018.06.020
更新日期:2018-07-01 00:00:00
abstract::Lanthanide-doped upconverting luminescent nanoparticles (UCNPs) are promising materials for optical imaging-guided drug delivery and therapy due to their unique optical and chemical properties. UCNPs absorb low energy near-infrared (NIR) light and emit high-energy shorter wavelength photons. Their special features all...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2012.05.007
更新日期:2013-05-01 00:00:00
abstract::Nanomedicine, which is an application of nanotechnologies in healthcare is developed to improve the treatments and lives of patients suffering from a range of disorders and to increase the successes of drug candidates. Within the nanotechnology universe, the remarkable unique and tunable properties of dendrimers have ...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2017.11.007
更新日期:2018-01-01 00:00:00
abstract::Gelatin is a denatured, biodegradable protein obtained by acid and alkaline processing of collagen. This processing affects the electrical nature of collagen, yielding gelatin with different isoelectric points (IEPs). When mixed with positively or negatively charged gelatin, an oppositely charged protein will ionicall...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章
doi:10.1016/s0169-409x(97)00125-7
更新日期:1998-05-04 00:00:00
abstract::While nanotechnology and the production of nanoparticles are growing exponentially, research into the toxicological impact and possible hazard of nanoparticles to human health and the environment is still in its infancy. This review aims to give a comprehensive summary of what is known today about nanoparticle toxicol...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2011.09.001
更新日期:2012-02-01 00:00:00
abstract::The ever increasing improvements of pharmaceutical formulations have been often obtained by means of the use of hydrogels. In particular, environmentally sensitive hydrogels have been investigated as "smart" delivery systems capable to release, at the appropriate time and site of action, entrapped drugs in response to...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2013.04.002
更新日期:2013-08-01 00:00:00
abstract::In principle, proton therapy offers a substantial clinical advantage over conventional photon therapy. This is because of the unique depth-dose characteristics of protons, which can be exploited to achieve significant reductions in normal tissue doses proximal and distal to the target volume. These may, in turn, allow...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2016.11.006
更新日期:2017-01-15 00:00:00
abstract::Cell-based therapy is emerging as a promising strategy for treating a wide range of human diseases, such as diabetes, blood disorders, acute liver failure, spinal cord injury, and several types of cancer. Pancreatic islets, blood cells, hepatocytes, and stem cells are among the many cell types currently used for this ...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2018.04.018
更新日期:2019-01-15 00:00:00
abstract::Human genome sequencing revealed that only ~1.5% of the DNA sequence coded for proteins. More and more evidence has uncovered that a substantial part of the 98.5% so-called "junk" DNAs actually code for noncoding RNAs. Two milestones, chemical drugs and protein drugs, have already appeared in the history of drug devel...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2013.11.006
更新日期:2014-02-01 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::Nanotechnology has the potential to open many novel diagnostic and treatment avenues for disorders of the central nervous system (CNS). In this review, we discuss recent developments in the applications of nanotechnology in CNS therapies, diagnosis and biology. Novel approaches for the diagnosis and treatment of neuro...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2019.02.009
更新日期:2019-08-01 00:00:00
abstract::Tissue engineering aims to provide structural and biomolecular cues to compromised tissues through scaffolds. An emerging biomolecular cue is that of RNA interference by which the expression of genes can be silenced through a potent endogenous pathway. Recombinant viral-based approaches in RNAi delivery exist; however...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2011.01.006
更新日期:2011-04-30 00:00:00
abstract::The delivery of biologics is an important component in the treatment of osteoarthritis and the functional restoration of articular cartilage. Numerous factors have been implicated in the cartilage repair process, but the uncontrolled delivery of these factors may not only reduce their full reparative potential but can...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2014.06.006
更新日期:2015-04-01 00:00:00
abstract::Analogues of luteinizing hormone-releasing hormone (LH-RH) have made possible new approaches to the treatment of some hormone-dependent cancers and diseases and conditions which result from inappropriate sex hormone levels. In the fields of both gynaecology and oncology, the development of sustained delivery depot sys...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章
doi:10.1016/s0169-409x(97)00056-2
更新日期:1997-10-13 00:00:00
abstract::The recent introduction of multi-photon microscopy coupled with advances in optics, computer sciences and the available fluorophores used to label molecules of interest have empowered investigators to study the dynamic events within the functioning kidney at cellular and subcellular levels. This emerging technique, wi...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2006.07.017
更新日期:2006-09-15 00:00:00
abstract::According to the latest report from the World Health Organization, an estimated 265,000 deaths still occur every year as a direct result of burn injuries. A widespread range of these deaths induced by burn wound happens in low- and middle-income countries, where survivors face a lifetime of morbidity. Most of the deat...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2017.08.001
更新日期:2018-01-01 00:00:00
abstract::Calcium phosphate cements are used as synthetic bone grafts, with several advantages, such as their osteoconductivity and injectability. Moreover, their low-temperature setting reaction and intrinsic porosity allow for the incorporation of drugs and active principles in the material. It is the aim of the present work ...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2012.01.008
更新日期:2012-09-01 00:00:00