Abstract:
:Direct pulmonary delivery is a promising step in developing effective gene therapies for respiratory disease. Gene therapies can be used to treat the root cause of diseases, rather than just the symptoms. However, developing effective therapies that do not cause toxicity and that successfully reach the target site at therapeutic levels is challenging. We have developed a polymer-DNA complex utilizing polyethylene imine (PEI) and DNA, which was then encapsulated into poly(lactic acid)-co-monomethoxy poly(ethylene glycol) (PLA-mPEG) microparticles via double emulsion, solvent evaporation. Then, the resultant particle size, porosity, and encapsulation efficiency were measured as a function of altering preparation parameters. Microsphere formation was confirmed from scanning electron micrographs and the aerodynamic particle diameter was measured using an aerodynamic particle sizer. Several formulations produced particles with aerodynamic diameters in the 0-5 μm range despite having larger particle diameters which is indicative of porous particles. Furthermore, these aerodynamic diameters correspond to high deposition within the airways when inhaled and the measured DNA content indicated high encapsulation efficiency. Thus, this formulation provides promise for developing inhalable gene therapies.
journal_name
AAPS PharmSciTechjournal_title
AAPS PharmSciTechauthors
Terry TL,Givens BE,Rodgers VGJ,Salem AKdoi
10.1208/s12249-018-1215-9subject
Has Abstractpub_date
2019-01-02 00:00:00pages
23issue
1issn
1530-9932pii
10.1208/s12249-018-1215-9journal_volume
20pub_type
杂志文章abstract::The purpose of this research was to use inline real-time near-infrared (NIR) to measure the moisture content of granules manufactured using a commercial production scale continuous twin-screw granulator fluid-bed dryer milling process. A central composite response surface statistical design was used to study the effec...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-011-9669-z
更新日期:2011-12-01 00:00:00
abstract::Pharmaceutical excipients contain reactive groups and impurities due to manufacturing processes that can cause decomposition of active drug compounds. The aim of this investigation was to determine if commercially available oral disintegrating tablet (ODT) platforms induce active pharmaceutical ingredient (API) degrad...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-013-0015-5
更新日期:2013-12-01 00:00:00
abstract::The process of developing an old drug for new indications is now a widely accepted strategy of shortening drug development time, reducing drug costs, and improving drug availability, especially for rare and neglected diseases. In this mini-review, we highlighted the impact of drug delivery systems in the fulfillment o...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章,评审
doi:10.1208/s12249-019-1333-z
更新日期:2019-02-15 00:00:00
abstract::The aim of this work is to improve the understanding of the physicochemical mechanisms involved in the functionality of cross-linked carboxymethyl sodium starch (CCSS) as a tablet super disintegrant (SD). The behavior and properties of this SD (medium uptake, disintegration times, particle size, and rheology) was inve...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-014-0121-z
更新日期:2015-04-01 00:00:00
abstract::Multidrug resistance is the major problem in cancer treatment nowadays. Compounds from plants are the new targets to solve this problem. Quercetin (QCT), quercetrin (QTR), and rutin (RUT) are potential anticancer flavonoids but their poor water solubility leads to less efficacy. In this study, the polymeric micelles o...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-020-01657-5
更新日期:2020-04-26 00:00:00
abstract::A combination of analytical and statistical methods is used to improve a tablet coating process guided by quality by design (QbD) principles. A solid dosage form product was found to intermittently exhibit bad taste. A suspected cause was the variability in coating thickness which could lead to the subject tasting the...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-011-9723-x
更新日期:2012-03-01 00:00:00
abstract::The specific aim of the present study was to investigate the biodegradation and biocompatibility characteristics of rosin, a natural film-forming polymer. Both in vitro as well as in vivo methods were used for assessment of the same. The in vitro degradation of rosin films was followed in pH 7.4 phosphate buffered sal...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/pt040455
更新日期:2003-10-22 00:00:00
abstract::Spironolactone is a drug derived from sterols that exhibits an incomplete oral absorption due to its low water solubility and slow dissolution rate. In this study, formulations of spironolactone with four disintegrants named as croscarmellose sodium, crospovidone, sodium starch glycolate and microcrystalline cellulose...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-012-9835-y
更新日期:2012-12-01 00:00:00
abstract::MUC1 gene encodes a transmembrane mucin glycoprotein that is overexpressed in human breast cancer and colon cancer. The objective of this study was to develop an in situ gel delivery system containing paclitaxel (PTX) and mucoadhesives for sustained and targeted delivery of anticancer drugs. The delivery system consis...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/pt070253
更新日期:2006-06-02 00:00:00
abstract::Itraconazole (ITZ) crystalline nanoparticles were prepared using relatively simple, low-cost sonoprecipitation technique, in which both the solvent and antisolvent were organic in nature. The effect of stabilizer type (hydroxypropyl methylcellulose, hydroxypropyl cellulose, Inutec SP1®, and pluronic F127), drying meth...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-011-9651-9
更新日期:2011-09-01 00:00:00
abstract::In this study, the resveratrol spray-dried emulsions were developed using a quality-by-design approach. Further, the product and process factors that affected the quality of the spray-dried emulsions were analyzed and illustrated using an Ishikawa diagram. The product and process risks were prioritized using a risk-ra...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-018-1220-z
更新日期:2018-12-18 00:00:00
abstract::The addition of polysorbate 20 (T20) is required to achieve "sink" conditions during a dissolution test for tablets with candesartan cilexetil (CC). Polysorbate 20 (0.35%-0.7% w/w) added to 0.05 mol/L of phosphate buffer pH 6.5 dramatically increased the apparent solubility of the drug from 0.8 μg/ml even to 353 μg/ml...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-014-0109-8
更新日期:2014-10-01 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 objective of the present investigation was to reduce the bitterness with improved dissolution, in acidic medium (pH 1.2), of mefloquine hydrochloride (MFL). Microparticles were prepared by coacervation method using Eudragit E (EE) as polymer and sodium hydroxide as precipitant. A 3(2) full factorial design was use...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-008-9052-x
更新日期:2008-01-01 00:00:00
abstract::This investigation was undertaken to evaluate practical feasibility of site specific pulmonary delivery of liposomal encapsulated Dapsone (DS) dry powder inhaler for prolonged drug retention in lungs as an effective alternative in prevention of Pneumocystis carinii pneumonia (PCP) associated with immunocompromised pat...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-007-9024-6
更新日期:2008-01-01 00:00:00
abstract::The ability to produce submicron particles of monoclonal antibodies of different sizes and shapes would enhance their application to pulmonary delivery. Although non-ionic surfactants are widely used as stabilizers in protein formulations, we hypothesized that non-ionic surfactants will affect the shape and size of su...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-012-9913-1
更新日期:2013-03-01 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::Bilayer nicotine mucoadhesive patches were prepared and evaluated to determine the feasibility of the formulation as a nicotine replacement product to aid in smoking cessation. Nicotine patches were prepared using xanthan gum or carbopol 934 as a mucoadhesive polymers and ethyl cellulose as a backing layer. The patche...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-010-9534-5
更新日期:2011-03-01 00:00:00
abstract::A simple but novel mixed surfactant system was designed to fabricate a self-nanoemulsifying drug delivery system (SNEDDS) based on hydrophilic-lipophilic balance (HLB) value. The impacts of HLB and molecular structure of surfactants on the formation of SNEDDS were investigated. After screening various oils and surfact...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-014-0078-y
更新日期:2014-04-01 00:00:00
abstract::Spherical granules (pellets) are quite useful in many pharmaceutical applications. The extrusion spheronisation technique is well established as a method of producing pellets of a spherical shape and narrow size distribution. After the extrusion, the cylindrical extrudates are transformed to spherical pellets by spher...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-012-9770-y
更新日期:2012-06-01 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::We determined the permeability coefficient of a model hydrophilic drug, calcein, encapsulated within saturated lipid-based nano-sized liposomes of various lipid profiles. We demonstrated that the addition of cholesterol to liposomes containing saturated lipids increased the permeability of the liposomal membrane to ca...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-016-0624-x
更新日期:2017-07-01 00:00:00
abstract::Pneumocystis carinii pneumonia (PCP) is a major opportunistic infection that affects patients with human immunodeficiency virus. Although orally administered dapsone leads to high hepatic metabolism, decreasing the therapeutic index and causing severe side effects, this drug is an effective alternative for the treatme...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-015-0283-3
更新日期:2015-10-01 00:00:00
abstract::Poly(vinyl alcohol) (PVA)-based formulations are used for pharmaceutical tablet coating with numerous advantages. Our objective is to study the stability of PVA-based coating films in the presence of acidic additives, alkaline additives, and various common impurities typically found in tablet formulations. Opadry® II ...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-011-9630-1
更新日期:2011-06-01 00:00:00
abstract::Nanotechnology is having a significant impact in the drug delivery systems and diagnostic devices. As most of the nanosystems are intended to be administered in vivo, there is a need for stability models, which could simulate the biological environment. Instability issues could lead to particle aggregation and in turn...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-016-0597-9
更新日期:2017-05-01 00:00:00
abstract::Freeze-dried immunoglobulin G (IgG) incorporating trehalose and human serum albumin (HSA) was statistically evaluated regarding the existence of synergism between additives on the stability profile. The levels of HSA (X1) and trehalose (X2) were independent variables. Aggregation following the process (Y1), after 2 an...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-019-1509-6
更新日期:2019-10-28 00:00:00
abstract::The aim of this work was to study the effect of the type of substituent of the cellulose ethers and the molecular mass on the state and dynamics of water in the respective hydrogels to specify the quantity of adsorbed water on the polymers or, more explicitly, to calculate the average number of water molecules bound t...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/pt030436
更新日期:2002-01-01 00:00:00
abstract::This study was performed to prepare and characterize the biotinylated Salmon calcitonin (sCT) for oral delivery and evaluate the hypocalcemic effect of biotinylated-sCTs in rats. Biotinylated sCTs was characterized by using high performance liquid chromatography (HPLC) and MALDITOF-MS. The effect of biotinylation on p...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-008-9165-2
更新日期:2008-01-01 00:00:00
abstract::A transdermal drug delivery system (TDDS) is generally designed to deliver an active pharmaceutical ingredient (API) through the skin for systemic action. Permeation of an API through the skin is controlled by adjusting drug concentration, formulation composition, and patch design. A bilayer, drug-in-adhesive TDDS des...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章
doi:10.1208/s12249-020-01682-4
更新日期:2020-06-04 00:00:00
abstract::Onychomycosis is a chronic disorder that is difficult to manage and hard to eradicate with perilous trends to relapse. Due to increased prevalence of HIV, use of immunosuppressant drugs and lifestyle-related factors, population affected with fungal infection of nail (Onychomycosis) happens to increase extensively in l...
journal_title:AAPS PharmSciTech
pub_type: 杂志文章,评审
doi:10.1208/s12249-019-1591-9
更新日期:2020-01-14 00:00:00