Controlled drug-release system based on pH-sensitive chloride-triggerable liposomes

Abstract

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.

Fliposomes: stimuli-triggered conformational flip of novel amphiphiles causes an instant cargo release from liposomes

“…Variation of the pKa of anionic lipids and their molar ratio can slightly modify the pH sensitivity. Another popular concept is based on the acidic hydrolysis of ortho-esters, acetals, hydrazones, vinyl ethers, or other acid-labile linkers in lipidic amphiphiles transforming the latter into destabilizing detergents or conical lipids (2,3,5,9,10,16,34,35). These reactions often require several hours to proceed, which may be a problem for timely drug release.…”

Recent development of biotin conjugation in biological imaging, sensing, and target delivery

“…1): (1) a cancer targeting moiety that can selectively guide the whole system into the tumor region; (2) an effector unit such as a reporter including fluorophore, an MRI contrast agent, and/or a pharmaceutical agent including a chemical drug, peptide, small interfering RNA (siRNA), or gene; and (3) a cleavable linker that is sufficiently stable to reduce cytotoxicity prior to its delivery to the target cells and cleaved enough to release its effector molecule upon arrival at the target and triggering by bio-species, pH, light, hypoxia, or other factors. [39][40][41] Recent studies demonstrated that thiol-containing amino acids, including glutathione (GSH), cysteine (Cys), and homocysteine (Hcy), are preferentially available in cancer cells to combat the gradual increase in reactive oxygen species (ROS) levels, maintaining the redox balance. Thus, a higher intracellular thiol concentration could be a characteristic element to distinguish between normal and cancer cells.…”

Stimulus-responsive liposomes as smart nanoplatforms for drug delivery applications

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