Begell House Inc.
Critical Reviews™ in Therapeutic Drug Carrier Systems
CRT
0743-4863
12
4
1995
Gene Introduction Into Animal Tissues
263-310
10.1615/CritRevTherDrugCarrierSyst.v12.i4.10
Mahito
Nakanishi
Department of Neurovirology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka, 565, Japan, and PRESTO, Research Development Corporation of Japan, 4-1-8 Hon-machi, Kawaguchi, Saitama, 332, Japan
gene therapy
viral vector
nonviral vector
hybrid vector
Gene therapy is an approach to treat various incurable diseases by expressing foreign genes directly into the human body. A number of vector systems to introduce genetic information into tissue cells have been developed for this purpose. This review provides a critical discussion of the characteristics of various vector systems and their possible application in human gene therapy.
Cyclodextrin Derivatives in Pharmaceutics
311-337
10.1615/CritRevTherDrugCarrierSyst.v12.i4.20
E.
Albers
Department of Pharmaceutics and Biopharmaceutics, Christian Albrecht University, Gutenbergstr. 76, D-24118 Kiel, Germany
B. W.
Muller
Department of Pharmaceutics and Biopharmaceutics, Christian Albrecht University, Gutenbergstr. 76, D-24118 Kiel, Germany
Cyclodextrins
2-hydroxypropyl-β-cyclodextrin
toxicity
solubilization
inclusion complexes
dissolution
stabilization
enhancer
pharmacokinetics
bioavailability
The current cyclodextrin (CD) literature is reviewed concerning synthesis, characterization, and pharmaceutical relevant applications of CD derivatives. Although natural CDs have been used extensively to improve pharmaceutical properties, the effects of chemically modified CDs on the solubility, dissolution rate, and stability of drugs are overproportional. Concerning the parenteral application, the major interest is focussed on highly water-soluble, randomly substituted hydroxyalkyl derivatives of β- and γ-CD such as 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD). Although the heptakis-(2,6-di-O-methyl)-β-cyclodextrin is applied in the pharmaceutical field, 2-HP-β-CD is predestined as a parenteral drug carrier owing to its weak hemolytic activity and intrinsically amorphous character. A minimal average degree of substitution is especially preferred when 2-HP-β-CD is used as solubilizer of pharmaceuticals for the use in parenteral applications. The influence of the type, degree, and pattern of substitution of the CDs, as well as substituent effects of the guest molecule is elucidated.
Targeting of Peptide and Protein Drugs to Specific Sites in the Oral Route
339-371
10.1615/CritRevTherDrugCarrierSyst.v12.i4.30
Jane P. F.
Bai
College of Pharmacy, University of Minnesota, Minneapolis, MN 55455
Li-Ling
Chang
College of Pharmacy, University of Minnesota, Minneapolis, MN 55455
Jian-Hwa
Guo
3M Pharmaceuticals, 3M Center 270-4S-02, St. Paul, MN 55144
apical efflux pump
site-dependent absorption
colonic proteolysis
Although the distal small intestine has less lumenal and apical proteolytic activities, it has high activities of some apical peptidases. Colonic proteolytic activities are substantial, but their nature is less understood. The small intestine has di- and tripeptide transporter, facilitating absorption, and P-glycoprotein, an efflux pump suggested to limit absorption of small peptides. Several peptide and nonpeptide drugs have higher absorption in the ileum; however, enhancement on their absorption by enhancers varies from site to site. Specific delivery systems can target drugs to the distal intestine utilizing distinct regional pHs and specific microbial enzymes, but the key is how to achieve a reliable release.
Subject Index
373
10.1615/CritRevTherDrugCarrierSyst.v12.i4.40
Author Index
375
10.1615/CritRevTherDrugCarrierSyst.v12.i4.50