Controlled drug-release system based on pH-sensitive chloride-triggerable liposomes.
New pH-sensitive lipids were synthesized and utilized in formulations of liposomes suitable for controlled drug release. These liposomes contain various amounts of NaCl in the internal aqueous compartments. The release of the drug model is triggered by an application of HCl cotransporter and exogenous physiologically relevant NaCl solution. HCl cotransporter allows an uptake of HCl by liposomes to the extent of their being proportional to the transmembrane Cl(-) gradient. Therefore, each set of liposomes undergoes internal acidification, which, ultimately, leads to the hydrolysis of the pH-sensitive lipids and content release at the desired time. The developed system releases the drug model in a stepwise fashion, with the release stages separated by periods of low activity. These liposomes were found to be insensitive to physiological concentrations of human serum albumin and to be nontoxic to cells at concentrations exceeding pharmacological relevance. These results render this new drug-release model potentially suitable for in vivo applications.
Department of Chemistry, Virginia Commonwealth University, 1001 West Main Street, Richmond, Virginia 23284, USA.
Mark P
MP
Wehunt
Christine A
CA
Winschel
Ali K
AK
Khan
Tai L
TL
Guo
Galya R
GR
Abdrakhmanova
Vladimir
V
Sidorov
D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000138:chemical synthesis / Q000737:chemistry*; D008081:Liposomes / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D012965:Sodium Chloride / Q000737:chemistry*; D049992:Sodium Chloride Symporters / Q000008:administration & dosage / Q000737:chemistry; D012996:Solutions / Q000008:administration & dosage / Q000737:chemistry
D003692:Delayed-Action Preparations; D008055:Lipids; D008081:Liposomes; D049992:Sodium Chloride Symporters; D012996:Solutions; D012965:Sodium Chloride