Abstract:
:Cationic liposomes have long been used as non-viral vectors for small interfering RNA (siRNA) delivery but are associated with high toxicity, less transfection efficiency, and in vivo instability. In this investigation, we have developed siRNA targeted to RRM1 that is responsible for development of resistance to gemcitabine in cancer cells. Effect of different lipid compositions has been evaluated on formation of stable and less toxic lipoplexes. Optimized cationic lipoplex (D2CH) system was comprised of dioleoyl-trimethylammoniumpropane (DOTAP), dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), hydrogenated soya phosphocholine (HSPC), cholesterol, and methoxy(polyethyleneglycol)2000-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (mPEG2000-DSPE). D2CH lipoplexes have shown particle size (147.5 ± 2.89 nm) and zeta potential (12.26 ± 0.54 mV) characteristics essential for their in vivo use. In vitro cytotoxicity study has shown low toxicity of developed lipoplexes as compared with lipofectamine-2000 up to N/P ratio as high as 7.5. Cell uptake studies and gene expression studies have confirmed intracellular availability of siRNA. In addition, developed lipoplexes also showed ~3 times less hemolytic potential as compared with DOTAP/DOPE lipoplexes at lipid concentration of 5 mg/mL. Lipoplexes also maintained particle size less than 200 nm on exposure to high electrolyte concentration and showed >70% siRNA retention in presence of serum showing siRNA protection conferred by lipoplexes. Furthermore, in vivo acute toxicity studies in mice showed that formulation was non-toxic up to a dosage of 0.75 mg of siRNA/kg as lipoplexes and 300 mg lipid/kg as blank liposomes indicating tolerability of lipoplexes at a dose much higher than required for therapeutic use. Promising results of this study warrant further investigation of developed siRNA lipoplexes for cancer treatment.
journal_name
AAPS PharmSciTechjournal_title
AAPS PharmSciTechauthors
Khatri N,Baradia D,Vhora I,Rathi M,Misra Adoi
10.1208/s12249-014-0193-9subject
Has Abstractpub_date
2014-12-01 00:00:00pages
1630-43issue
6issn
1530-9932journal_volume
15pub_type
杂志文章abstract::Niacin (nicotinic acid, NA) is administered orally as an antihyperlipidemic agent in extended-release (ER) tablets in high doses. Due to rapid absorption and extensive metabolism (non-linear pharmacokinetics), the drug plasma levels are highly variable, which may correlate with side effects. Interestingly, this errati...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-019-1600-z
更新日期:2020-01-27 00:00:00
abstract::The aim of this work was the formulation and characterization of alginate (ALG)-doxycycline (DOX) hydrogel microparticles (MPs) embedded into Pluronic F127 thermogel for DOX intradermal sustained delivery. ALG-DOX MPs were formed by adding a solution of the drug into a 1.5% polymer solution while stirring. The MPs wer...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-009-9361-8
更新日期:2010-03-01 00:00:00
abstract::Solubility challenge for a poorly water-soluble drug gets further intensified when it is weakly ionic because the most common solubility enhancement technique, salt formation, becomes less feasible. Salt screening for such drugs often concludes with either a difficult to crystalize salt or an unstable salt, leading th...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-017-0808-z
更新日期:2018-01-01 00:00:00
abstract::Incorporation of drug-loaded nanoparticles into swellable and respirable microparticles is a promising strategy to avoid rapid clearance from the lung and achieve sustained drug release. In this investigation, a copolymer of polyethylene glycol grafted onto phthaloyl chitosan (PEG-g-PHCs) was synthesized and then self...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-014-0176-x
更新日期:2014-12-01 00:00:00
abstract::The purpose of this study was to develop formulations and systematically evaluate in vitro performances of buccoadhesive patches of propranolol hydrochloride using the hydrophobic polymer Eudragit L-100 as the base matrix. The hydrophilic polymers Carbopol 934 and polyvinyl pyrrolidone (PVP) K30 were incorporated into...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/pt0802045
更新日期:2007-06-22 00:00:00
abstract::Loteprednol etabonate (LE) is a soft corticosteroid that maintains therapeutic activity with much reduced adverse effects. Yet, its ocular bioavailability is hindered by its poor aqueous solubility. Early attempts of LE complexation with cyclodextrins (CDs) did not involve the study of the effects of various complexat...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-016-0589-9
更新日期:2017-05-01 00:00:00
abstract::The objective of this study was to investigate the release behaviour of propranolol hydrochloride from psyllium matrices in the presence hydrophilic polymers. The dissolution test was carried out at pH 1.2 and pH 6.8. Binary mixtures of psyllium and hydroxypropyl methylcellulose (HPMC) used showed that an increase in ...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-011-9687-x
更新日期:2011-12-01 00:00:00
abstract::A folic acid-conjugated paclitaxel (PTX)-doxorubicin (DOX)-loaded nanostructured lipid carrier(s) (FA-PTX-DOX NLCs) were prepared by using emulsion-evaporation method and extensively characterized for particle size, polydispersity index, zeta potential, and % entrapment efficiency which were found to be 196 ± 2.5 nm, ...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-018-1185-y
更新日期:2018-11-01 00:00:00
abstract::The purpose of the present study was to design mucoadhesive gliadin nanoparticles (GNP) containing amoxicillin and to evaluate their effectiveness in eradicating Helicobacter pylori. GNP-bearing amoxicillin (AGNP) was prepared by desolvation method. The effect of process variables such as gliadin concentration and ini...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/pt050232
更新日期:2004-04-07 00:00:00
abstract::Capsaicin has multiple pharmacological activities including antioxidant, anticancer, and anti-inflammatory activities. However, its clinical application is limited due to its poor aqueous solubility, gastric irritation, and low oral bioavailability. This research was aimed at preparing sustained-release matrix pellets...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-015-0352-7
更新日期:2016-04-01 00:00:00
abstract::Transdermal drug delivery is an emerging field in the pharmaceutical remit compared with conventional methods (oral and parenteral). Microneedle (MN)-based devices have gained significant interest as a strategy to overcome the skin's formidable barrier: the stratum corneum. This approach provides a less invasive, more...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章,评审
doi:10.1208/s12249-019-1560-3
更新日期:2019-12-05 00:00:00
abstract::The purpose of this study was to investigate physicochemical characteristics and in vitro release of zidovudine from monolithic film of Eudragit RL 100 and ethyl cellulose. Films included 2.5% or 5% (w/w) zidovudine of the dry polymer weight were prepared in various ratios of polymers by solvent evaporation method fro...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-008-9179-9
更新日期:2009-01-01 00:00:00
abstract::Herein, we report the successful development of a novel nanosystem capable of an efficient delivery and temperature-triggered drug release specifically aimed at cancer. The water-soluble 130.1 ± 0.2 nm iron oxide nanoparticles (IONPs) were obtained via synthesis of a monodispersed iron oxide core stabilized with tetra...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-014-0131-x
更新日期:2014-08-01 00:00:00
abstract::The aim of the present study was to develop a spilanthol emulsion and investigate the effect of oil and drug physicochemical properties on drug release and skin retention at molecular level. Formulation factors including oil, emulsifier, and humectant were investigated by in vitro skin retention/permeation study and t...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-019-1454-4
更新日期:2019-06-20 00:00:00
abstract::Although several guidelines do exist for freeze-drying process development and scale-up, there are still a number of issues that require additional attention. The objective of this review article is to discuss some emerging process development and scale-up issue with emphasis on effect of load condition and freeze-dry...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章,评审
doi:10.1208/s12249-011-9599-9
更新日期:2011-03-01 00:00:00
abstract::Lipid-based drug carriers are likely to have influence on bioavailability through enhanced solubilization of the drug in the gastrointestinal tract. The study was designed to investigate the lipid formulation digestibility in the simulated gastro intestinal media. Fenofibrate was formulated in representative Type II, ...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-012-9787-2
更新日期:2012-06-01 00:00:00
abstract::The purpose of this study was to design and investigate the transdermal controlled release cubic phase gels containing capsaicin using glycerol monooleate (MO), propylene glycol (1,2-propanediol, PG), and water. Three types of cubic phase gels were designed based on the ternary phase diagram of the MO-PG-water system,...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-010-9481-1
更新日期:2010-09-01 00:00:00
abstract::Chemical penetration enhancers are widely used in transdermal drug delivery system. However, few studies have focused on changes of concentration in chemical penetration enhancers. In this study, the effect of concentrations of enhancers on drug release and its mechanism were investigated. Zolmitriptan (ZOL) was used ...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-019-1370-7
更新日期:2019-04-25 00:00:00
abstract::Transcutaneous immunization using a microneedle device presents a promising alternative to syringe-based injection of vaccines. The aim of this study was to investigate the effective immune response elicited after application of tetanus toxoid antigen-loaded dissolvable microneedles (TT-MN) in mice model. Dissolvable ...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-019-1471-3
更新日期:2019-07-22 00:00:00
abstract::Next to the coating formulation, process conditions play important roles in determining coating quality. This study aims to develop an operational window that separates layering from agglomeration regimes and, furthermore, the one that leads to the best coating quality in a fluidized bed coater. The bed relative humid...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-009-9250-1
更新日期:2009-01-01 00:00:00
abstract::In this study, liquid crystalline nanoparticles (LCN) have been proposed as new carrier for topical delivery of finasteride (FNS) in the treatment of androgenetic alopecia. To evaluate the potential of this nanocarrier, FNS-loaded LCN was prepared by ultrasonication method and characterized for size, shape, in vitro r...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-012-9888-y
更新日期:2013-03-01 00:00:00
abstract::For the prediction of the air and product temperatures, the product moisture, and the air humidity during a coating process in a Bohle Lab-Coater, a model was developed. The purpose of this work was to determine the limit moisture, the critical moisture, and the constant for the exchange rate between both zones and to...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/pt070243
更新日期:2006-05-05 00:00:00
abstract::The current study explains the development of sorbitan monostearate and sesame oil-based organogels for topical drug delivery. The organogels were prepared by dissolving sorbitan monostearate in sesame oil (70°C). Metronidazole was used as a model antimicrobial. The formulations were characterized using phase contrast...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-014-0223-7
更新日期:2015-04-01 00:00:00
abstract::Effectiveness of CNS-acting drugs depends on the localization, targeting, and capacity to be transported through the blood-brain barrier (BBB) which can be achieved by designing brain-targeting delivery vectors. Hence, the objective of this study was to screen the formulation and process variables affecting the perfor...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-016-0481-7
更新日期:2016-12-01 00:00:00
abstract::The classically used nontargeted chemotherapeutic approach to pancreatic cancer has a dual drawback of suboptimal drug delivery at the target site and the systemic side effects produced by the unfettered exposure of the drug to healthy tissue. This study has the objective of developing novel poly(2-ethyl-2-oxazoline) ...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-020-01745-6
更新日期:2020-08-10 00:00:00
abstract::The purpose of this research was to use our previously validated dynamic injection apparatus as a rapid method for screening pH-adjusted formulations of a new vancomycin analog, Van-An, for their potential to precipitate upon dilution. In 1 vial, Van-An was reconstituted according to the manufacturer's instructions. I...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/pt070105
更新日期:2006-03-01 00:00:00
abstract::The performance of dioctyl sodium sulfosuccinate (aerosol OT) in the development of a pharmaceutically acceptable, stable, self-emulsifying water continuous microemulsion with high dilution efficiency was assessed. A pseudoternary microemulsion system was constructed using aerosol OT/medium-chain triglycerides with ol...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/pt040111
更新日期:2003-01-01 00:00:00
abstract::The primary objective of this study was to evaluate the effect of drug loading on the release of leuprolide acetate from an injectable polymeric implant, formed in situ, and efficacy of the released drug in suppressing serum testosterone levels in dogs for at least 90 days. An additional objective was to compare the o...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/pt010101
更新日期:2000-02-28 00:00:00
abstract::The objective of this study was to determine the influence of mechanical stresses simulating gastrointestinal contraction forces of 2.0 N (stomach) and 1.2 N (intestine) on the gel properties and drug release characteristics from sustained release swelling and eroding hydrophilic matrices during dissolution studies. T...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-014-0225-5
更新日期:2015-04-01 00:00:00
abstract::This study focused on the synthesis and characterization of a natural polymeric system employing the interpenetrating polymer network (IPN) comprising curcumin as a bioactive. Biopolymers and actives such as chitosan, hypromellose, citric acid, genipin, and curcumin were used to develop an effective, biodegradable, an...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-014-0170-3
更新日期:2014-12-01 00:00:00