Abstract:
OBJECTIVES:Clinical translation of siRNA therapeutics has been severely limited due to the lack of stable and sustained siRNA delivery systems. Furthermore, when nanocarrier systems with siRNA are administered systemically to treat diseases, insufficient doses reach the target tissue. Here we report the successful development of a new nanocarrier system for the management of fibrosis. METHODS:The new carrier has a hydroxyapatite core, with alternating layers of siRNA and a cationic peptide. The siRNA used here targets secreted protein acidic and rich in cysteine (SPARC), a key matricellular protein involved in the regulation of collagen fibrillogenesis and assembly. We have also used FRET studies to elucidate the fate of the particles inside cells, including the mechanistic details of layer-by-layer detachment. RESULTS:In vitro studies using murine conjunctiva fibroblasts show sustained release over 2 weeks, and that such released siRNA sustained SPARC knockdown without affecting cell growth, and maintained siRNA presence in the cells for at least two weeks with a single-dose treatment. Release studies of siRNA from particles in vitro gave insight on how the particles delivered prolonged gene-silencing effects. CONCLUSION:A single treatment of the layer-by-layer nanoparticle designed can achieve sustained gene silencing over 2 weeks. Localized delivery of stabilized siRNA with sustained-release capabilities opens the door for many other applications of siRNA-based gene regulation.
journal_name
Expert Opin Drug Delivjournal_title
Expert opinion on drug deliveryauthors
Tan YF,Lee YS,Seet LF,Ng KW,Wong TT,Venkatraman Sdoi
10.1080/17425247.2018.1518426subject
Has Abstractpub_date
2018-10-01 00:00:00pages
937-949issue
10eissn
1742-5247issn
1744-7593journal_volume
15pub_type
杂志文章abstract:BACKGROUND:The present work aims to formulate nanostructured lipid carriers (NLCs) exhibiting high skin deposition and high inherent antioxidant potential to repurpose the use of melatonin hormone and some antioxidant oils in the treatment of androgenic alopecia (AGA). RESEARCH DESIGN AND METHODS:NLCs were characteriz...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章
doi:10.1080/17425247.2018.1517740
更新日期:2018-10-01 00:00:00
abstract:INTRODUCTION:Use of pre-filled syringes as both a packaging and delivery system for pharmaceutical drug products is accelerating. Pre-filled syringes must meet the quality and suitability for use requirements for both systems, including compatibility with the drug product. Relevant incompatibilities between pre-filled ...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章,评审
doi:10.1517/17425247.2014.928281
更新日期:2014-10-01 00:00:00
abstract::Cancer is the second leading cause of death in the US. Currently, protocols for cancer treatment include surgery to remove diseased and suspect tissues, focused radiation, systemic chemotherapy, immunotherapy and their combinations. With conventional chemotherapy, it is almost impossible to deliver anticancer drugs sp...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章,评审
doi:10.1517/17425240903085128
更新日期:2009-08-01 00:00:00
abstract:INTRODUCTION:The development of therapeutics for central nervous system (CNS) disorders is still considered a challenging area in drug development due to insufficient translocation through the blood-brain barrier (BBB). Under normal conditions, BBB restrict the penetration of more than 98% of blood-borne molecules incl...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章,评审
doi:10.1080/17425247.2018.1444601
更新日期:2018-04-01 00:00:00
abstract::The Socrates Intensive Programme offers annual courses focusing on the specific aspects of innovative therapeutics. The 2004 meeting was coordinated by the University of Parma and covered various subjects in the field of advanced drug delivery and pharmaceutical technology, including sessions on biopharmaceutics, phar...
journal_title:Expert opinion on drug delivery
pub_type:
doi:10.1517/17425247.1.1.185
更新日期:2004-11-01 00:00:00
abstract:INTRODUCTION:Peptide and protein microarray and microneedle array technology provides direct information on protein function and potential drug targets in drug discovery and delivery. Because of this unique ability, these arrays are well suited for protein profiling, drug target identification/validation and studies of...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章,评审
doi:10.1517/17425247.2013.797405
更新日期:2013-08-01 00:00:00
abstract:INTRODUCTION:Amphiphilic block copolymers are recognized components of parenteral drug nanocarriers. However, their performance in oral administration has barely been evaluated to any great extent. AREAS COVERED:This review provides an overview of the methods used to prepare drug-loaded polymeric micelles and to evalu...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章,评审
doi:10.1517/17425247.2015.960841
更新日期:2015-02-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Efficient systemic delivery of low-molecular-mass therapeutics to neuronal tissue remains a central issue not only to drug development but also to the chronic treatment of a range of neurodegenerative disorders. AREAS COVERED IN THIS REVIEW:This review discusses the potential of using RNA inter...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章,评审
doi:10.1517/17425247.2010.490554
更新日期:2010-07-01 00:00:00
abstract:INTRODUCTION:In the therapy of clinical diseases such as cancer, it is important to deliver drugs directly to tumor sites in order to maximize local drug concentration and reduce side effects. This objective may be realized by using 'smart' nanoparticles (NPs) as drug delivery systems, because they enable dramatic conf...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章,评审
doi:10.1517/17425247.2015.1071352
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:With the incorporation of edge activators into the lipid bilayer structure, elasticity properties are given to liposomes. Regardless of the debate over the precise permeation mechanism of elastic liposomes, these vesicles have been proven to enhance drug permeation into or through skin in most cases. AREA...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章,评审
doi:10.1517/17425247.2013.779252
更新日期:2013-06-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Since the 1950s, ultrasonic nebulizers have played an important role in pulmonary drug delivery. As the process in which aerosol droplets are generated is independent and does not require breath-actuation, ultrasonic nebulizers, in principle, offer the potential for instantaneously fine-tuning t...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章,评审
doi:10.1517/17425247.2010.485608
更新日期:2010-06-01 00:00:00
abstract:INTRODUCTION:Delivery of macromolecular drugs is an important field in medical research. However, macromolecules are usually unable to cross the cell membrane without the assistance of a delivery system. Cell penetrating peptides (CPPs) are unique tools to gain access to the cell interior and deliver a bioactive cargo ...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章,评审
doi:10.1517/17425247.2016.1125879
更新日期:2016-01-01 00:00:00
abstract:INTRODUCTION:Topical drug delivery is a challenging area with many advantages such as avoidance of first passage effect, stabilization of blood concentrations and attainment of local therapeutic effect with fewer side effects. Despite all these advantages, topical drug delivery remains limited to few molecules, since s...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章,评审
doi:10.1080/17425247.2016.1182489
更新日期:2016-08-01 00:00:00
abstract::Functionalised carbon nanotubes (f-CNTs) are emerging as new tools in the field of nanobiotechnology and nanomedicine. This is because they can be easily manipulated and modified by encapsulation with biopolymers or by covalent linking of solubilising groups to the external walls and tips. The possibility of incorpora...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章,评审
doi:10.1517/17425247.1.1.57
更新日期:2004-11-01 00:00:00
abstract:INTRODUCTION:Most vaccines are administered by intramuscular injection using a hypodermic needle and syringe. Some limitations of this procedure include reluctance to be immunized because of fear of needlesticks, and concerns associated with the safe disposal of needles after their use. Skin delivery is an alternate ro...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章,评审
doi:10.1517/17425247.2014.885947
更新日期:2014-04-01 00:00:00
abstract:BACKGROUND:We hypothesized if phagocytosis of liposomes by macrophages could be mitigated through incorporation of a CD47 mimicry peptide (Self peptide: SP) on the surface of liposomes. METHODS:Thin film hydration method followed by extrusion was used to prepare nanoliposomes, and Dox encapsulation in liposomes was do...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章
doi:10.1080/17425247.2020.1772749
更新日期:2020-07-01 00:00:00
abstract:INTRODUCTION:Considering that the number of patients afflicted by posterior eye diseases is increasing, effective drug delivery is currently in high clinical demand. Topical administration has been identified as the preferred option, while sufferingfrom multiple barriers. The development of nanoparticle-based drug deli...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章,评审
doi:10.1080/17425247.2018.1496080
更新日期:2018-07-01 00:00:00
abstract::FlexTouch® (FT) is a new prefilled insulin pen with the unique characteristic of no extendable push button at any dose setting and consequently a low activation force. Its technical features along with health care professionals' and patients' preferences in comparison to other traditionally used devices for insulin de...
journal_title:Expert opinion on drug delivery
pub_type: 社论
doi:10.1517/17425247.2014.894505
更新日期:2014-05-01 00:00:00
abstract:BACKGROUND:Injectable life-saving drugs should not be exposed to temperatures <4°C/39°F or >30°C/86°F. Frequently, weather conditions exceed these temperature thresholds in many countries. Insulin is to be kept at 4-8°C/~ 39-47°F until use and once opened, is supposed to be stable for up to 31 days at room temperature ...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章
doi:10.1080/17425247.2017.1316261
更新日期:2017-06-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Spontaneously constructed from block copolymers in aqueous media, the polymer micelle has been extensively studied as a potential carrier of poorly water-soluble drugs, but cellular uptake pathways and stability of micelles in blood have not yet been clearly understood. An in-depth insight into ...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章,评审
doi:10.1517/17425240903380446
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:The treatment of hard tissue defects, especially those of bone and cartilage, induced by infections or tumors remains challenging. Traditional methods, including debridement with systematic chemotherapy, have shortcomings owing to their inability to eliminate infections and high systematic toxicity. AREA ...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章
doi:10.1080/17425247.2021.1860015
更新日期:2021-01-19 00:00:00
abstract:INTRODUCTION:Drug release and oral absorption of drugs with pH-dependent solubility are influenced by the conditions in the gastrointestinal tract. In some cases, poor oral absorption has been observed for these drugs, causing insufficient drug efficacy. The pH-modification of a formulation could be a promising approac...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章,评审
doi:10.1517/17425247.2014.881798
更新日期:2014-04-01 00:00:00
abstract:BACKGROUND:Inhalation of microparticulate dosage forms can be effectively used in the treatment of respiratory and systemic diseases. OBJECTIVE:Disease states investigated for treatment by inhalation of microparticles were reviewed along with the drugs' pharmacological, pharmacokinetic and physical chemical properties...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章,评审
doi:10.1517/17425247.5.3.269
更新日期:2008-03-01 00:00:00
abstract:BACKGROUND:Therapeutic peptides have great potential as anticancer agents owing to their ease of rational design and target specificity. However, their utility in vivo is limited by low stability and poor tumor penetration. OBJECTIVE:The authors review the development of peptide inhibitors with potential for cancer th...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章,评审
doi:10.1517/17425240903143745
更新日期:2009-10-01 00:00:00
abstract:INTRODUCTION:The emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) is a major health issue and continues to be a global health concern. Despite significant advancements in treatment modalities, ~1.6 million deaths worldwide occur due to TB infection. This is bec...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章,评审
doi:10.1080/17425247.2019.1609937
更新日期:2019-05-01 00:00:00
abstract:INTRODUCTION:Nanocomposite microparticles are intelligent carriers utilised for pulmonary drug delivery. These carriers are composed of drug-encapsulated nanoparticles dispersed in microstructures of polysaccharides. Upon administration, the inhaled microparticles can penetrate and be deposited deeply in the lung due t...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章,评审
doi:10.1517/17425247.2016.1102224
更新日期:2016-01-01 00:00:00
abstract:INTRODUCTION:Overactive bladder affects a significant portion of the population and results in prescribing of numerous medications for its treatment. Traditional drug delivery systems used in therapy are associated with multiple commonly reported side effects. Adherence rates with use of these medications are low. It i...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章,评审
doi:10.1517/17425247.2016.1130033
更新日期:2016-01-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Vascular delivery of several classes of therapeutic agents may benefit from carriage by red blood cells (RBC), for example, drugs that require delivery into phagocytic cells and those that must act within the vascular lumen. The fact that several protocols of infusion of RBC-encapsulated drugs a...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章,评审
doi:10.1517/17425241003610633
更新日期:2010-04-01 00:00:00
abstract::Noninvasive, transient and local image-guided blood-brain barrier disruption can be accomplished using focused ultrasound exposure with intravascular injection of preformed microbubbles. MRI-guided blood-brain barrier disruption has been demonstrated and has been shown to heal in within a few hours after exposure. The...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章,评审
doi:10.1517/17425247.4.1.27
更新日期:2007-01-01 00:00:00
abstract:INTRODUCTION:Nanocarrier-based delivery systems offer multiple benefits to overcome limitations of the traditional drug dosage forms, such as protection of the drug, enhanced bioavailability, targeted delivery to disease site, etc. Nanocarriers have exhibited tremendous successes in targeted delivery of therapeutics to...
journal_title:Expert opinion on drug delivery
pub_type: 杂志文章
doi:10.1080/17425247.2021.1828339
更新日期:2020-10-08 00:00:00