Conjugation of isoniazid to a zinc phthalocyanine via hydrazone linkage for pH-dependent liposomal controlled release

Tuberculosis (TB) remains the leading cause of mortality from infectious diseases. Extended TB treatment and frequent adverse effects, due to poor bioavailability of anti-tubercular drugs (ATBDs), represent the main rationales behind liposomal encapsulation for controlled delivery. Liposomes have been reported as potential vehicles for targeted delivery of ATBDs due to their rapid uptake by macrophages, which are known as the main host cells for TB causative agent (Mycobacterium tuberculosis). Additionally, the need for controlled release of ATBDs arises because leakage is part of the key liposome challenges for hydrophilic compounds like isoniazid (INH). In this study, INH was conjugated to a highly hydrophobic photosensitizer, zinc (II) phthalocyanine (PC), through hydrazone bonding. The obtained conjugate (PC–INH) was encapsulated in liposomes by film hydration method. PC–INH loaded liposomes (PILs) were characterized using dynamic light scattering, transmission electron microscopy, energy-dispersive X-ray spectrometry and UV–Vis absorption spectrometry, which was used also for estimation of encapsulation efficiency (%EE). INH release was evaluated in different pH media using dialysis. Particle size, zeta potential and %EE of PILs were about 506 nm, − 55 mV and 72%, respectively. Over 12 h, PILs exhibited 22, 41, 97 and 100% of INH, respectively, released in pH 7.4, 6.4, 5.4 and 4.4 media. This pH-dependent behavior is attractive for site-specific delivery. These findings suggest the conjugation of chemotherapeutics to phthalocyanines using pH-labile linkages as a potential strategy for liposomal controlled release

Photodynamic therapy for cancer: principles, clinical applications and nano technological approaches

Photodynamic therapy (PDT) is a clinically approved, minimally invasive procedure that can exert a cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizer (PS) followed by irradiation with light at wavelengths within of the PS absorption band. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature, and induction of a local inflammatory reaction. Clinical studies reveal that PDT can be curative, particularly in early stage tumors, can prolong survival in patients with inoperable cancers, and can significantly improve quality of life. Unfortunately, most PS lack specificity for tumor cells and this can result in undesirable side effects in healthy tissues. Furthermore, due to their mostly planar structure, PS form aggregates with low photoactivity in an aqueous environment. Nanotechnology offers a great opportunity in PDT based on the concept that a nanocarrier can drive therapeutic concentrations of PS to the tumor cells without generating any harmful effect in vivo. Currently, several nanoscale carriers made of different materials such as lipids, polymers, metals, and inorganic materials have been proposed in nano-PDT. Each type of system highlights pros and cons and should be selected on the basis of delivery requirements. In the following, we describe the principle of PDT and its application in the treatment of cancer. Then, we illustrate the main systems proposed for nano-PDT that demonstrated potential in preclinical models together with emerging concepts for their advanced design