Begell House Inc.
Critical Reviews™ in Therapeutic Drug Carrier Systems
CRT
0743-4863
20
1
2003
Mitochondrial-Targeted Drug and DNA Delivery
62
10.1615/CritRevTherDrugCarrierSyst.v20.i1.10
Volkmar
Weissig
Northeastern University, Bouve College of Health Sciences, School of Pharmacy, Department of Pharmaceutical Sciences, 360 Huntington Avenue, Mugar 211, Boston MA 02115, USA
The field of mitochondrial research is currently among the fastest growing disciplines in biomedicine. Approximately 12,000 articles on mitochondria have been published since the beginning of the new millennium. What brings mitochondria into the limelight of the scientific community? Since the end of the 1980s, a series of key discoveries has been made that have rekindled the scientific interest in this long-known cell organelle. It has become increasingly evident that mitochondrial dysfunction contributes to a variety of human disorders, ranging from neurodegenerative and neuromuscular diseases, obesity, and diabetes to ischemia-reperfusion injury and cancer. Moreover, since the middle of the 1990s, mitochondria, the “power houses” of the cell, have also become accepted as the cells’ “arsenal,” reflecting their increasingly acknowledged key role during apoptosis. Based on these recent developments in mitochondrial research, increased pharmacological and pharmaceutical efforts have lead to the emergence of “mitochondrial medicine” as a new field of biomedical research. Targeting of biologically active molecules to mitochondria in living cells will open avenues for manipulating mitochondrial functions, which may result in the selective protection, repair, or eradication of cells. This review gives a comprehensive overview of current strategies of mitochondrial targeting and their possible therapeutic applications.
Ethosomes: New Prospects in Transdermal Delivery
40
10.1615/CritRevTherDrugCarrierSyst.v20.i1.20
Biana
Godin
Department of Pharmaceutics, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 91120, Israel
Elka
Touitou
Department of Pharmaceutics, School of Pharmacy; The David R. Bloom Center for Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel
Ethosomes are noninvasive delivery carriers that enable drugs to reach the deep skin layers and/or the systemic circulation. Although ethosomal systems are conceptually sophisticated, they are characterized by simplicity in their preparation, safety, and efficacy—a combination that can highly expand their application. Ethosomes are soft, malleable vesicles tailored for enhanced delivery of active agents. This article reviews work carried out in vitro, in vivo, in animal models, and in humans with various ethosomal systems incorporating a wide range of drugs. Because of their unique structure, ethosomes are able to encapsulate and deliver through the skin highly lipophilic molecules such as cannabinoids, testosterone, and minoxidil, as well as cationic drugs such as propranolol and trihexyphenidil. Results obtained in a double-blind two-armed randomized clinical study showed that treatment with the ethosomal acyclovir formulation signi. cantly improved all the evaluated parameters. Preliminary studies with plasmids and insulin revealed that the ethosomal carrier may be used for enhanced delivery of these agents. In further work, the ethosomal technology was broadened to introduce agents into cultured cells and microorganisms. Enhanced delivery of bioactive molecules through the skin and cellular membranes by means of an ethosomal carrier opens numerous challenges and opportunities for the research and future development of novel improved therapies.