Hyperthermia mediated liposomal drug delivery

Abstract

Drug delivery systems have been developed for cancer therapy in an attempt to increase the tumour drug concentration while limiting systemic exposure. Liposomes have achieved passive targeting of solid tumours through enhanced vascular permeability, which is greatly augmented by hyperthermia. However, anti-tumour efficacy has often been limited by slow release of bioavailable drug within the tumour. Local hyperthermia has become the most widely used stimulus for triggered release of liposomal drugs, through the use of specific lipids, polymers or other modifiers. A temperature-sensitive liposome containing doxorubicin has been shown to release 100% of contents through stabilized membrane pores within 10-20 s at 41 degrees C. This formulation has exhibited dramatic improvements in pre-clinical drug delivery and tumour regression and is now in clinical trials. Significantly, recent studies show that this liposome, in combination with local hyperthermia, exhibits vascular shutdown as a mechanism of anti-tumour effect that is not observed with free doxorubicin.

Structural insights on biologically relevant cationic membranes by ESR spectroscopy

“…Heating leads to the melting of lipid molecules to a fluid liquid-crystalline phase, in which van der Waals interactions are decreased, hydrocarbon chain conformational disorder predominates and translational and flip-flop motions occur more frequently (Mason 1998;Evans and Wennerström 1999). These reversible gel-fluid transitions alter membrane permeability and can be important for drug delivery applications (Anyarambhatla and Needham 1999;Ponce et al 2006).…”

Tumor pH-responsive flower-like micelles of poly(l-lactic acid)-b-poly(ethylene glycol)-b-poly(l-histidine)

“…In tumor treatment the micelles system has proven effective in regression of tumor size while minimizing damage to the healthy tissues [4] and is being actively investigated in conjunction with hyperthermia [5], ultrasound [6], specific enzyme-induced cleavable bonds [7][8][9], and specific ligands or antibodies [10][11][12][13] for active targeting purposes.…”

“…In all measurements (involving either invasive or noninvasive methods) of the pH e of human and animal solid tumors, more than 80% of all measured values consistently fall below a pH of 7.2 [27][28][29]. The development of pH-sensitive drug-carriers therefore maybe a unique strategy and confer advantages over using external stimuli, such as hyperthermia [5] and ultrasound [6] which require exact location of tumors for triggered release [30].…”

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“…For triggered release of liposomal drugs, local hypothermia is used greatly with specific lipids, polymers, or other molecules. [40] Another new development of liposomal drug delivery is, their properties of specific binding to a target cell-like tumor cells or to a specific molecule such as antibodies and proteins. Some liposomes like stealth liposome are used to carry water soluble drugs like doxorubicin, mitoxantrone to achieve their maximum Liposome can function through surface too to enhance receptor-mediated endocytosis by binding with ligands such as antibodies, proteins, and carbohydrates [13] effects.…”