Barriers to nonviral gene delivery.

Abstract:

:The use of various synthetic lipids and polymers to deliver DNA for gene therapy applications has been the subject of intense examination for the last 15 years. Our understanding of the processes involved in the delivery of DNA, although still limited, can be described in terms of specific physical and chemical barriers encountered along the delivery pathway. Successful engagement of this pathway involves avoiding inactivation in the extracellular compartment and initial favorable interactions with the cell surface. Internalization of the delivery system by endocytosis results in a poorly defined endosomal trafficking process which, if not escaped, leads to degradation of the therapeutic DNA in lysosomes. For the small fraction of material that is able to escape this vesicular trafficking pathway, the cytosol provides additional physical and metabolic barriers to further trafficking to the nucleus. Finally, nuclear uptake has been demonstrated to be a significant barrier to gene delivery. In this review, we outline in greater detail the various processes involved in each step and describe various formulation variables that have been explored to overcome these delivery barriers to nonviral gene delivery.

journal_name

J Pharm Sci

authors

Wiethoff CM,Middaugh CR

doi

10.1002/jps.10286

subject

Has Abstract

pub_date

2003-02-01 00:00:00

pages

203-17

issue

2

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(16)31169-8

journal_volume

92

pub_type

杂志文章,评审
  • Fluorescence assay of nitrofurantoin with o-aminothiophenol in plasma and urine.

    abstract::A fluorescence method is presented for the determination of nitrofurantoin based on conversion of the drug to a fluorescent substance. The method requires 0.1-0.5 ml of plasma or diluted urine and is 10 times more sensitive than the commonly used colorimetric method. ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600690134

    authors: Watari N,Funaki T,Kaneniwa N

    更新日期:1980-01-01 00:00:00

  • Drying rates of tablet granulations II: effect of particle size and granular densities.

    abstract::The effects of the granule size and density on the drying rate kinetics of tablet granulations were studied using lactose and sulfathiazole granules prepared with acacia mucilage and providone solution. The drying rate kinetics consisted of three distinct phases of drying when the drying rate was platted against remai...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600640631

    authors: Opankunle WO,Bhutani BR,Bhatia VN

    更新日期:1975-06-01 00:00:00

  • Uptake of acetazolamide by human erythrocytes in vitro.

    abstract::The binding of acetazolamide to human erythrocytes was studied in vitro. Blood and plasma samples were analyzed by electron-capture GLC. At 37 degrees, drug equilibrated between plasma and erythrocytes in approximately 40 min. The effect of plasma concentration on the steady-state level of drug within the erythrocytes...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600660532

    authors: Wallace SM,Reigelman S

    更新日期:1977-05-01 00:00:00

  • Micro and macro GLC determination of ethambutol in biological fluids.

    abstract::Previously available GLC methods for ethambutol may only be used to measure quantities of drugs much greater than those found in biological fluids such as plasma and dialysate. A previously published GLC method for plasma samples is extended to measure ethambutol in dialysate. A second GLC method, involving derivatiza...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600670407

    authors: Lee CS,Benet LZ

    更新日期:1978-04-01 00:00:00

  • Synthesis, physicochemical properties, and antitumor activities of analogs of 1-phenyl-3-benzyl-3-methyltriazenes.

    abstract::To study the effect of substituents on the antitumor activities of analogs of 1-phenyl-3-benzyl-3-methyltriazenes, a series of compounds was designed and synthesized in which the substituent on the 1-phenyl was an electron-withdrawing group and the substituent on the 3-benzyl had a broad range of physicochemical prope...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600661017

    authors: Dunn WJ 3rd,Greenberg MJ

    更新日期:1977-10-01 00:00:00

  • Species difference in GI motor response to somatostatin.

    abstract::Acute experiments were performed on overnight fasted chloralose-urethan anesthetized dogs, cats, rabbits, and rats. Under these conditions, somatostatin practically abolished gastric contractions and decreased GI tonus in all species examined. The canine duodenum, jejunum, and ileum exhibited only a contractile respon...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600680913

    authors: Tansy MF,Martin JS,Landin WE,Kendall FM

    更新日期:1979-09-01 00:00:00

  • Zinc(II) in saliva: determination of concentrations produced by different formulations of zinc gluconate lozenges containing common excipients.

    abstract::A study of the pH of saliva produced by humans sucking hard candy lozenges containing zinc gluconate and citric acid demonstrated the probability that the formulation delivered an insignificant amount of the contained zinc as Zn2+. This could account for the negative results of several clinical studies of this lozenge...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600810205

    authors: Zarembo JE,Godfrey JC,Godfrey NJ

    更新日期:1992-02-01 00:00:00

  • Design and optimization of self-nanoemulsifying delivery system to enhance quercetin hepatoprotective activity in paracetamol-induced hepatotoxicity.

    abstract::The present study aimed to develop optimized quercetin (QT)-loaded self-nanoemulsifying drug delivery system (SNEDDS) that offers protective effect against liver damage. Solubility study of QT in different oils, surfactants, and cosurfactants was performed. Ternary phase mixtures of the selected components were constr...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.23834

    authors: Ahmed OA,Badr-Eldin SM,Tawfik MK,Ahmed TA,El-Say KM,Badr JM

    更新日期:2014-02-01 00:00:00

  • GLC determination of (-)-1-cyclopropylmethyl-4-(3-trifluoromethylthio-5H-dibenzo [a,d]cyclohepten-5-ylidene)piperidine in human plasma and urine.

    abstract::(-)-1-Cyclopropylmethyl-4-(3-trifluoromethylthio-5H-dibenzo [a,d]cyclohepten-5-ylidene)piperidine (MK-160) was extracted from human plasma and urine with petroleum ether and quantitated by GLC using a nitrogen-sensitive detector. A homologue of the drug served as the internal standard. The method is specific for the d...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600720725

    authors: Hucker HB,Hutt JE

    更新日期:1983-07-01 00:00:00

  • A Physiologically Based Pharmacokinetic Modeling Approach to Predict Drug-Drug Interactions of Buprenorphine After Subcutaneous Administration of CAM2038 With Perpetrators of CYP3A4.

    abstract::CAM2038, FluidCrystal injection depot, is an extended release formulation of buprenorphine given subcutaneously every 1 week (Q1W) or every 4 weeks (Q4W). The purpose of this research was to predict the magnitude of drug-drug interaction (DDI) after coadministration of a strong CYP3A4 inducer or inhibitor using physio...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2017.10.035

    authors: Liu T,Gobburu JVS

    更新日期:2018-03-01 00:00:00

  • Vacuum-Induced Surface Freezing for the Freeze-Drying of the Human Growth Hormone: How Does Nucleation Control Affect Protein Stability?

    abstract::In the present work, the effect of controlled nucleation on the stability of human growth hormone (hGH) during freeze-drying has been investigated. More specifically, the vacuum-induced surface freezing technique has been compared to conventional freezing, both with and without an annealing step. Size exclusion chroma...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2019.04.014

    authors: Oddone I,Arsiccio A,Duru C,Malik K,Ferguson J,Pisano R,Matejtschuk P

    更新日期:2020-01-01 00:00:00

  • Disposition of norgestimate in the presence and absence of ethinyl estradiol after oral administration to humans.

    abstract::The disposition of radioactivity following oral administration of 14C-norgestimate was compared to that following administration of the drug in combination with 3H-ethinyl estradiol in humans. Seven normal, healthy female subjects were each administered one capsule orally containing 14C-norgestimate either alone (74.4...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600671020

    authors: Weintraub HS,Abrams LS,Patrick JE,McGuire JL

    更新日期:1978-10-01 00:00:00

  • Stabilization of human papillomavirus virus-like particles by non-ionic surfactants.

    abstract::Human papillomavirus (HPV) virus-like-particles (VLPs) produced by recombinant expression systems are promising vaccine candidates for prevention of cervical cancers as well as genital warts. At high protein concentrations, HPV VLPs, comprised of the viral capsid protein L1 and expressed and purified from yeast, are p...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.20377

    authors: Shi L,Sanyal G,Ni A,Luo Z,Doshna S,Wang B,Graham TL,Wang N,Volkin DB

    更新日期:2005-07-01 00:00:00

  • Cactus alkaloids XXXIII: beta-phenethylamines from the Guatemalan cactus Pilosocereus maxonii.

    abstract::TLC analysis of extracts of Pilosocereus maxonii (Rose) Byles and Rowley detected six identifiable alkaloids. Preparative TLC aided in the crystallization of the hydrochlorides of N-methyl-3,4-dimethoxyphenethylamine, N-methyl-3-methoxytyramine, and N,N-dimethyl-3-methoxytyramine. Traces of 3,4-dimethoxyphenethylamine...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600661037

    authors: Pummangura S,Nichols DE,McLaughlin JL

    更新日期:1977-10-01 00:00:00

  • Characterization of the properties of cocaine in blood: blood clearance, blood to plasma ratio, and plasma protein binding.

    abstract::As part of a study to examine cocaine disposition and interaction with ethanol, it was necessary to characterize various properties of cocaine in the blood of the experimental animal. All studies were conducted using blood from healthy adult male Sprague-Dawley rats. Cocaine was incubated in whole blood at 37 degrees ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1021/js960026h

    authors: Sukbuntherng J,Martin DK,Pak Y,Mayersohn M

    更新日期:1996-06-01 00:00:00

  • Solasodine stability under conditions of saponin hydrolysis.

    abstract::The extent of formation of solasodiene from solasodine upon treatment with hydrochloric acid under various conditions was determined. The diene formed was assayed by using the characteristic extinction at 236 nm. Diene formation was effected by the acid concentration and the boiling point of the solvent used. Optimal ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600670839

    authors: Segal R,Breuer A,Milo-Goldzweig I

    更新日期:1978-08-01 00:00:00

  • A hot-melt extruded intravaginal ring for the sustained delivery of the antiretroviral microbicide UC781.

    abstract::Microbicide intravaginal rings (IVRs) are a promising woman-controlled strategy for preventing sexual transmission of human immunodeficiency virus (HIV). An IVR was prepared and developed from polyether urethane (PU) elastomers for the sustained delivery of UC781, a highly potent nonnucleoside reverse transcriptase in...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.22781

    authors: Clark MR,Johnson TJ,McCabe RT,Clark JT,Tuitupou A,Elgendy H,Friend DR,Kiser PF

    更新日期:2012-02-01 00:00:00

  • Control of Globular Protein Thermal Stability in Aqueous Formulations by the Positively Charged Amino Acid Excipients.

    abstract::The positively charged amino acids are commonly used excipients in biopharmaceutical formulations for stabilization of therapeutic proteins, yet the mechanisms for their modulation of protein stability are poorly understood. In this study, both lysine and histidine are shown to affect the thermal stability of myoglobi...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2016.09.013

    authors: Platts L,Darby SJ,Falconer RJ

    更新日期:2016-12-01 00:00:00

  • Metal complexes of anhydrotetracycline. 1. A spectrometric study of the Cu(II) and Ni(II) complexes.

    abstract::Anhydrotetracycline (AHTC), one of the major toxic decomposition products of the antibiotic tetracycline, contains several potential binding sites to metal ions. The acidity constants of the ligand were calculated in aqueous medium (I = 0.1 M) at 25 and 37 degrees C. We found pKa1 = 3.23 +/- 0.08, pKa2 = 5.94 +/- 0.09...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600830306

    authors: de Siqueira JM,Carvalho S,Paniago EB,Tosi L,Beraldo H

    更新日期:1994-03-01 00:00:00

  • A site-directed mutagenesis study of drug-binding selectivity in genetic variants of human alpha(1)-acid glycoprotein.

    abstract::Human alpha(1)-acid glycoprotein (AGP), a major carrier of many basic drugs in circulation, consists of at least two genetic variants, namely A and F1*S variant. Interestingly, the variants of AGP have different drug-binding properties. The purpose of this study was to identify the amino acid residues that are respons...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.21697

    authors: Nishi K,Ueno M,Murakami Y,Fukunaga N,Akuta T,Kadowaki D,Watanabe H,Suenaga A,Maruyama T,Otagiri M

    更新日期:2009-11-01 00:00:00

  • Structural and thermal characterization of zolpidem hemitartrate hemihydrate (Form E) and its decomposition products by laboratory X-ray powder diffraction.

    abstract::The crystal structure of zolpidem hemitartrate hemihydrate (I, Form E) has been solved from high-resolution laboratory powder diffraction data. It crystallizes in the orthorhombic P2(1)2(1)2(1) space group with a = 22.4664(6) A, b = 26.0420(7) A, and c = 7.4391(1) A. Protonation of zolpidem molecules could not be unam...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.21883

    authors: Halasz I,Dinnebier RE

    更新日期:2010-02-01 00:00:00

  • Predicting With Confidence: Using Conformal Prediction in Drug Discovery.

    abstract::One of the challenges with predictive modeling is how to quantify the reliability of the models' predictions on new objects. In this work we give an introduction to conformal prediction, a framework that sits on top of traditional machine learning algorithms and which outputs valid confidence estimates to predictions ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2020.09.055

    authors: Alvarsson J,Arvidsson McShane S,Norinder U,Spjuth O

    更新日期:2021-01-01 00:00:00

  • The effect of mutations on the structure of insulin fibrils studied by Fourier transform infrared (FTIR) spectroscopy and electron microscopy.

    abstract::Fibril formation (aggregation) of human and bovine insulin and six human insulin mutants in hydrochloric acid were investigated by visual inspection, Thioflavin T fluorescence spectroscopy, transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) spectroscopy. The fibrillation tendencies of the wi...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.10238

    authors: Garriques LN,Frokjaer S,Carpenter JF,Brange J

    更新日期:2002-12-01 00:00:00

  • Supersaturating drug delivery systems: fast is not necessarily good enough.

    abstract::An emerging technology subtype that has been adopted by formulators to address low-solubility issues is the supersaturating drug delivery system; this system is based on the "spring" and "parachute" design elements, which have been applied to lipid-based formulations, S(M)EDDS, solid dispersions, nano-based systems, a...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.22750

    authors: Augustijns P,Brewster ME

    更新日期:2012-01-01 00:00:00

  • In vitro binding of chloroquine to rat muscle preparations.

    abstract::Chloroquine (7-chloro-4-[[4-(diethylamino)-1-methylbutyl]amino]quinoline; CQ) accumulates in the insoluble fraction of rat muscle homogenates with an equilibrium distribution ratio of 7.8 L/kg. This is of a similar magnitude to muscle:plasma ratios observed in vivo. Uptake is approximately linear, even up to concentra...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600751109

    authors: MacIntyre AC,Cutler DJ

    更新日期:1986-11-01 00:00:00

  • Synthesis of tetracycline ring A analogs.

    abstract::Studies directed at the synthesis of tetracycline ring A analogs are described. 4-Carbethoxycyclohexane-1,3-dione was converted to the ethyl urethan dispiro[1,3-dioxolane-2,2'-cyclohexane-4',2"(1,3)-dioxolane]-1'-carbamic acid ethyl ester via the dispiro[1,3-dioxolane-2,2'-cyclohexane-4'-2"(1,3)-dioxolane]-1'-carboxyl...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600700508

    authors: Moskalyk RE,Mak AL,Chatten LG,Locock RA

    更新日期:1981-05-01 00:00:00

  • Physicochemical characterisation, drug polymer dissolution and in vitro evaluation of phenacetin and phenylbutazone solid dispersions with polyethylene glycol 8000.

    abstract::Poor water solubility leads to low dissolution rate and consequently, it can limit bioavailability. Solid dispersions, where the drug is dispersed into an inert, hydrophilic polymer matrix can enhance drug dissolution. Solid dispersions were prepared using phenacetin and phenylbutazone as model drugs with polyethylene...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.22613

    authors: Khan S,Batchelor H,Hanson P,Perrie Y,Mohammed AR

    更新日期:2011-10-01 00:00:00

  • Role of Solvent Selection on Crystal Habit of 5-Aminosalicylic Acid-Combined Experimental and Computational Approach.

    abstract::Many active pharmaceutical ingredients exhibit a needle-like (acicular) crystal habit, which can significantly complicate their downstream processing. In this study, the acicular crystal habit of a model active pharmaceutical ingredient, 5-aminosalicylic acid (5-ASA), was modified by addition of selected organic solve...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2017.12.005

    authors: Pudasaini N,Parker CR,Hagen SU,Bond AD,Rantanen J

    更新日期:2018-04-01 00:00:00

  • Drug diffusion through cystic fibrotic mucus: steady-state permeation, rheologic properties, and glycoprotein morphology.

    abstract::One manifestation of cystic fibrosis (CF) is the presence of a viscid mucus secretion in the lungs. The clearance of this mucus is significantly slower than in "normals" due to uncoordinated beating of the cilia and the increased viscosity of the mucus. In these studies, the permeabilities of p-aminosalicylic acid, is...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1021/js950381s

    authors: Bhat PG,Flanagan DR,Donovan MD

    更新日期:1996-06-01 00:00:00

  • Oral apomorphine delivery from solid lipid nanoparticles with different monostearate emulsifiers: pharmacokinetic and behavioral evaluations.

    abstract::Apomorphine, a dopamine receptor agonist for treating Parkinson's disease, has very poor oral bioavailability (<2%) due to the first-pass effect. The aim of this work was to investigate whether the oral bioavailability and brain regional distribution of apomorphine could be improved by utilizing solid lipid nanopartic...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.22285

    authors: Tsai MJ,Huang YB,Wu PC,Fu YS,Kao YR,Fang JY,Tsai YH

    更新日期:2011-02-01 00:00:00