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 Scijournal_title
Journal of pharmaceutical sciencesauthors
Wiethoff CM,Middaugh CRdoi
10.1002/jps.10286subject
Has Abstractpub_date
2003-02-01 00:00:00pages
203-17issue
2eissn
0022-3549issn
1520-6017pii
S0022-3549(16)31169-8journal_volume
92pub_type
杂志文章,评审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
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journal_title:Journal of pharmaceutical sciences
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journal_title:Journal of pharmaceutical sciences
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journal_title:Journal of pharmaceutical sciences
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doi:10.1002/jps.2600670839
更新日期:1978-08-01 00:00:00
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...
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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...
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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...
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journal_title:Journal of pharmaceutical sciences
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