pH-sensitive Liposomes for Drug Delivery in Cancer Treatment

Abstract

In recent years, liposomes have been employed with growing success as pharmaceutical carriers for antineoplastic drugs. One specific strategy used to enhance in vivo liposome-mediated drug delivery is the improvement of intracytoplasmic delivery. In this context, pH-sensitive liposomes (pHSLip) have been designed to explore the endosomal acidification process, which may lead to a destabilization of the liposomes, followed by a release of their contents into the cell cytoplasm. This review considers the current status of pHSLip development and its applicability in cancer treatment, focusing on the mechanisms of pH sensitivity and liposomal composition of pHSLip. The final section will discuss the application of these formulations in both in vitro and in vivo studies of antitumor efficacy.

Experimental design of a liposomal lipid system: A potential strategy for paclitaxel-based breast cancer treatment

“…It is well known that the interstitial fluids of a number of tumors in humans and animals have an ambient pH varying between 6.0 and 7.0, whereas in normal tissue the extracellular pH is approximately 7.4. These liposomes also have the potential to undergo destabilization at the endosomal vesicles (pH values below 5.0), thereby preventing their degradation at the lysosomal level and promoting the release of the drug into the cytoplasm, in turn inducing cellular death [2,16]. The initial accumulation of pH-sensitive liposomes is achieved by passive targeting by means of the enhanced permeability and retention (EPR) effect.…”

“…Cytotoxic drugs affect both healthy and cancerous tissue; as a result, they often cause severe side effects, which limit their clinical application [1,2].…”

Inducible release of particulates from liposomes using the mechanosensitive channel of large conductance and l-α-lysophosphatidylcholine

“…Currently, the most promising liposome preparations are "stimulus-triggered" liposomes (e.g., pH, redox state or temperature triggered liposomes), with pH-triggered liposomes being the most actively researched (Chiang and Lo 2014;Obata et al 2010;Sanchez et al 2011;Yuba et al 2011). pH-triggered liposomes can be inefficient due to the reliance on lipid bilayer destabilization using either a narrow acidic pH range found near tumors or via endosomal uptake, which can result in cargo degradation due to the low pH environment that follows (Ferreira Ddos et al 2013;Straubinger 1993). Redox-triggered liposomes are designed to respond to the overproduction of quinone reductases found in cancers and inflammatory diseases (Fitzsimmons et al 1996;Ong et al 2008).…”

Liposome percutaneous penetration in vivo

“…3,4 They increase therapeutic and decrease side effects of potent drugs. 2,[5][6][7] Drugs encapsulation within alters their pharmacokinetics, 8 and changes on liposome surface can enhance drug targeting. Liposomes have been used in medical applications as agents in "passive tumor targeting," "vaccine adjuvants," "sustained release depot at point of injection," "antiinfective agents," carriers for "targeting regional lymph nodes," and "gene vehicles."…”