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

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Abstract

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.

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Acknowledgements

This work was supported by the National Research Foundation of South Africa through the DST Innovation and Priority Research Areas Masters and Doctoral Scholarship, and the Sandisa Imbewu Programme of Rhodes University. Advice from the NGO Förderverein Uni Kinshasa e. V.- BEBUC/Else-Kroener-Fresenius Stiftung and Holger-Poehlmann is gratefully acknowledged.

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  1. Center for Chemico- and Bio-Medicinal Research (CCBR), Department of Chemistry, Rhodes University, PO Box 94, Grahamstown, Eastern Cape, 6140, South Africa

    Christian Isalomboto Nkanga & Rui Werner Maçedo Krause

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  1. Christian Isalomboto Nkanga
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  2. Rui Werner Maçedo Krause
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Correspondence to Rui Werner Maçedo Krause.

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Nkanga, C.I., Krause, R.W.M. Conjugation of isoniazid to a zinc phthalocyanine via hydrazone linkage for pH-dependent liposomal controlled release. Appl Nanosci 8, 1313–1323 (2018). https://doi.org/10.1007/s13204-018-0776-y

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