Abstract:
:siRNA based therapeutics is an emerging class of molecules with a high potential for fulfilling the promise of gene medicine. The high selectivity of siRNAs for their targets and subsequent gene ablation has been effectively demonstrated in a wide range of pre-clinical models. siRNA delivery in vivo has been most successfully achieved using lipid-based drug delivery systems. These lipid based formulations are designed to entrap siRNA molecules, ensure stability in in vitro and in vivo milieu, facilitate uptake, enhance cellular targeting, and facilitate delivery in the desired intracellular compartment. As more siRNA-based therapeutics enters the clinic with the associated regulatory scrutiny, there is a clear need to develop well-characterized systems that ensure consistent quality and thus reliable performance. Early clinical trials can be conducted using formulations with limited short-term stability manufactured on a small scale. However, a thorough understanding of the factors that influence the structure and stability of these particulate formulations is required to prevent any issues with optimization of large-scale industrial manufacturing, scale-up, and long-term shelf-life required to support large clinical trials and eventual market use. As newer targets for siRNA are identified and novel lipids are synthesized to optimize their in vivo efficiency, concomitant development of bio-physical methodologies that can improve understanding of the assembly and stability of these complex systems is critical. Along with bio-physical characterization, these assays are also required to reliably design, screen, develop and optimize formulations. Physicochemical characterization thus forms the basis of developing an effective analytical control strategy for siRNA delivery systems. In this review, analytical techniques used to characterize lipid-based siRNA delivery systems are discussed in detail. The importance of these physicochemical characterization techniques and analytical assays is explained. Case studies illustrating their use in siRNA formulation development and optimization are presented.
journal_name
Int J Pharmjournal_title
International journal of pharmaceuticsauthors
Kapoor M,Burgess DJ,Patil SDdoi
10.1016/j.ijpharm.2011.09.032subject
Has Abstractpub_date
2012-05-01 00:00:00pages
35-57issue
1eissn
0378-5173issn
1873-3476pii
S0378-5173(11)00881-7journal_volume
427pub_type
杂志文章,评审abstract::A novel, efficient delivery system for iron (Fe2+) was developed using the alginate biopolymer. Iron loaded alginate nanoparticles were synthesized by a controlled ionic gelation method and was characterized with respect to particle size, zeta potential, morphology and encapsulation efficiency. Successful loading was ...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2016.09.053
更新日期:2016-11-20 00:00:00
abstract::The simultaneous skin permeation of drug and penetration enhancer have been studied in vitro. Simple formulations of mefenamic acid in PEG400 incorporating various proportions of ethanol or 1,8-cineole were prepared and applied to porcine ear skin in diffusion cells under infinite conditions. Receptor phases were assa...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2006.05.018
更新日期:2006-09-14 00:00:00
abstract::The objective of this study was to investigate the presence of amino acid transporters on the corneal epithelium and to enhance corneal drug absorption through prodrug modification targeted to the amino acid transporters. SIRC was used as a model cell line representing the corneal epithelium. Uptake studies were carri...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(02)00405-2
更新日期:2002-10-24 00:00:00
abstract::It has been demonstrated that orally administered cholestyramine is distributed throughout the stomach and provides prolonged gastric residence via mucoadhesion. Gamma scintigraphy was used to compare the gastric emptying and residence of this resin with two formulations known to exhibit retentive or bioadhesive prope...
journal_title:International journal of pharmaceutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0378-5173(00)00600-1
更新日期:2001-01-05 00:00:00
abstract::Immune stimulating complexes and/or ISCOM matrices (adjuvant nanoparticles without antigen as a structural component) found potential applications as nasal vaccine adjuvant/delivery system owing to virus like particulate structure and saponin as potent Th1 adjuvant. One of important limiting factor for nasal vaccine d...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2010.07.051
更新日期:2010-10-15 00:00:00
abstract::Insulin, a key peptide hormone that conjointly with its receptor regulates blood glucose levels, is used as the major means to treat diabetes. This therapeutic hormone may undergo different chemical modifications during industrial processes, pharmaceutical formulation, and through its endogenous storage in the pancrea...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章,评审
doi:10.1016/j.ijpharm.2018.06.023
更新日期:2018-08-25 00:00:00
abstract::A formyl group-ended poly(DL-lactic acid) (PLA-aldehyde), synthesized in the same manner as reported previously, was utilized to produce the polymeric marker for PLA-related nanoparticles. Namely, pyrene-ended poly(DL-lactic acid) (PLA-pyrene) was prepared as a polymeric marker by the reductive amination of PLA-aldehy...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2008.03.011
更新日期:2008-06-24 00:00:00
abstract::A sensitive atmospheric pressure chemical ionization liquid chromatographic-mass spectrometric (APCI-LC-MS) assay with positive ion mode has been developed for the determination of nifedipine in human plasma. In this method, nifedipine was extracted from human plasma using diethyl ether with dimethoxanate as the inter...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.ijpharm.2007.03.053
更新日期:2007-08-16 00:00:00
abstract::The objective of the present study was to determine the optimum composition for sustained-release of tamsulosin hydrochloride from microparticles intended for orally disintegrating tablets. Microparticles were prepared from an aqueous ethylcellulose dispersion (Aquacoa®), and an aqueous copolymer based on ethyl acryla...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2011.01.053
更新日期:2011-04-15 00:00:00
abstract:PURPOSE:The objectives of this study were to establish a new preparation method for poly(DL-lactide-co-glycolide) (PLGA) nanoparticles by modifying the spontaneous emulsification solvent diffusion (SESD) method and to elucidate the mechanism of nanoparticle formation on the basis of the phase separation principle of PL...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(99)00187-8
更新日期:1999-10-05 00:00:00
abstract::The objective of this study was to evaluate the combination of pH-dependent and time-dependent polymers as a single coating for design of colon delivery system of indomethacin pellets. Eudragit S100 and Eudragit L100 were used as pH-dependent polymers and Eudragit RS was used as a time-dependent polymer. A statistical...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2006.05.011
更新日期:2006-08-31 00:00:00
abstract::Proteins generally will tend to aggregate under a variety of environmental conditions in comparison with small drug molecules. The extent of aggregation is dependent on many factors that can be broadly classified as intrinsic (primary, secondary, tertiary or quaternary structure) or extrinsic (environment in which pro...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章,评审
doi:10.1016/j.ijpharm.2010.02.025
更新日期:2010-05-10 00:00:00
abstract::A new class of surfactants with glycerate headgroups, that form viscous lyotropic liquid crystalline phases in excess water, have been investigated for their potential to provide sustained release matrices for depot drug delivery. Oleyl glycerate and phytanyl glycerate were used as representative surfactants of this n...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2005.11.033
更新日期:2006-02-17 00:00:00
abstract::Etoposide (ETO), a widely used anti-cancer drug, is constrained by its low aqueous solubility and by side effects from both the drug and its solubilizing excipients. In this study, a recently discovered natural solubilizer rubusoside (RUB) was used to achieve the solubilization of ETO. Dynamic light scattering and fre...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2012.06.013
更新日期:2012-09-15 00:00:00
abstract::In this investigation, Nutlin-3 (Nut3), a novel antitumor drug with low water solubility (<0.1mg/L at 25°C), was loaded into liposomes (Lipo-Nut3), polymeric nanoparticles (NPs-Nut3) and nanoparticles engineered with an antibody direct against Syndecan-1/CD 138 (Syn-NPs-Nut3) to obtain carriers targeted to PEL (primar...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2015.05.029
更新日期:2015-07-25 00:00:00
abstract::Spherical hydroxyapatite cores were prepared by using carboxylic acid terminated half-generation poly(amidoamine) (PAMAM) dendrimer as templates or crystal modifiers. The hydroxyapatite cores were characterized by infrared spectroscopy (IR), X-ray diffraction (XRD) and transmission electron microscopy (TEM). The spher...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(02)00235-1
更新日期:2002-07-08 00:00:00
abstract::To optimize the in vivo ocular transfection efficiency of plasmid DNA (pDNA)/cationic liposome complexes, N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA)/dioleoylphosphatidylethanolamine (DOPE) (1:1 molar ratio) liposomes and DOTMA/cholesterol (Chol) (1:1 molar ratio) liposomes were prepared with...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2004.03.013
更新日期:2004-07-08 00:00:00
abstract::Melanoma is resistant to chemotherapeutics with poor prognosis and high potential of metastasis. Photodynamic therapy (PDT) represents a localized therapeutic modality, as cytotoxicity occurs when light activates photosensitizer (PS) at the tumour site. The aim of this study is dermal delivery of a high molecular weig...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2018.06.057
更新日期:2018-09-05 00:00:00
abstract::Proquazone, a poorly wettable compound, was used as a model drug in the search for reasons to develop a capsule or tablet formulation. The capsules were filled with proquazone as active ingredient, with lactose monohydrate (200 mesh) as filler and with magnesium stearate as lubricant. The tablet was made out of a gran...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2004.09.006
更新日期:2004-12-09 00:00:00
abstract::Endothelial progenitor cells (EPCs) contribute to ischemic tissue repair by paracrine secretion up-regulated by hypoxia. In this study we use novel nanoparticles (NPs) as carriers for a controlled release of EPC secretome (CM) to improve their angiogenic properties. The in vivo effect in ischemic hindlimb rat model wa...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2018.03.015
更新日期:2018-05-05 00:00:00
abstract::Additive manufacturing (AM) offers significant potential benefits in the field of drug delivery and pharmaceutical/medical device manufacture. Of AM processes, 3D inkjet printing enables precise deposition of a formulation, whilst offering the potential for significant scale up or scale out as a manufacturing platform...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2017.06.085
更新日期:2017-08-30 00:00:00
abstract::The purpose of this study was to prepare solid SMEDDS (sSMEDDS) particles produced by spray-drying using maltodextrin (MD), hypromellose (HPMC), and a combination of the two as a solid carrier. Naproxen (NPX) as the model drug was dissolved (at 6% concentration) or partially suspended (at 18% concentration) in a liqui...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2015.03.015
更新日期:2015-05-15 00:00:00
abstract::Local drug delivery into oral cavity offers many advantages over systemic administration in treatment of the oral infections. In this study, monolayer and bilayered mucoadhesive film and wafer formulations were developed as local drug delivery platforms using chitosan and hydroxypropyl methylcellulose (HPMC). Cefuroxi...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2019.01.029
更新日期:2019-03-25 00:00:00
abstract::Blend uniformity analysis (BUA) is a routine and highly regulated aspect of pharmaceutical production. In most instances, it involves quantitative determination of individual components of a blend in order to ascertain the mixture ratio. This approach often entails the use of costly and sophisticated instrumentation a...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2012.07.073
更新日期:2012-11-15 00:00:00
abstract::Near-infrared chemical imaging (NIR-CI) with high-speed cameras based on the push-broom acquisition principle is a rapidly-evolving and can be used for a variety of purposes, from classification (and sorting) of products to mapping spatial distribution of materials. The present study examined if NIR-CI is suitable for...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2016.12.003
更新日期:2017-02-25 00:00:00
abstract::Because of their properties, ionic liquids (ILs) (Ranke et al.) offer many advantages in topical drug delivery systems. For example, ionic liquids can be used to increase the solubility of sparingly soluble drugs and to enhance their topical and transdermal delivery. Furthermore, ILs can be used either to synthesize a...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2012.10.035
更新日期:2013-01-30 00:00:00
abstract::A novel agglomeration process of pulverized pharmaceutical powders into subsieve-sized agglomerates (microagglomeration) was designed for manufacturing highly drug-incorporated core particles for subsequent microencapsulation by film-coating. The microagglomeration of pulverized phenacetin powder, whose mass median di...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(99)00006-x
更新日期:1999-04-15 00:00:00
abstract::This investigation is a contribution to standardization in in vitro drug penetration measurements using excised human skin and to statistical treatment of the observations. The wide variations observed in measurements of drug accumulation in and drug permeation through the stratum corneum are caused not only by analyt...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(00)00558-5
更新日期:2000-11-19 00:00:00
abstract::This is the first report on the efficacy of a new controlled release system developed for rasagiline mesylate (RM) in a rotenone-induced rat model of Parkinson's disease (PD). PLGA microspheres in vitro released RM at a constant rate of 62.3 μg/day for two weeks. Intraperitoneal injection of rotenone (2 mg/kg/day) to ...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2011.07.029
更新日期:2011-10-31 00:00:00
abstract::To understand the quality, efficacy, and safety of liposomal drugs, it is necessary to develop a robust and accurate method for the separation and the quantification of unencapsulated and liposome-associated drugs (or liposomal encapsulated drugs). Conventional methods involve separation of unencapsulated and liposome...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2018.07.019
更新日期:2018-10-05 00:00:00