Preparation, Characterization, and In Vitro pH-sensitivity Evaluation of Superparamagnetic Iron Oxide Nanoparticle- Misonidazole pH-sensitive Liposomes

Author(s): Bibo Li , Biqiang Li , Daiying He , Changyan Feng , Zhibin Luo* , Mei He* .

Journal Name: Current Drug Delivery

Volume 16 , Issue 3 , 2019

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Abstract:

Background: The use of Misonidazole (MISO), the first and a potential hypoxic tumor cell radiosensitizer, has been limited by peripheral neurotoxicity, thus discouraging phase III clinical trials.

Objective: To develop a targeted drug delivery and tracing System with pH-sensitive liposomes (SpHLs) and Superparamagnetic Iron Oxide Nanoparticles (SPIONs) to counter MISO-related adverse effects and to enable tracing under magnetic resonance.

Methods: SPION-MISO-SpHLs were prepared by a reverse evaporation and freeze-thawing method. HPLC and phenanthroline spectrophotometry were established for MISO and Fe determination. The characterization and in vitro pH-sensitivity of SPION-MISO-SpHLs were evaluated.

Results: The maximal entrapment efficiencies of MISO and SPIONs in SPION-MISO-SpHLs were 30.2% and 23.7%, respectively. The cumulative release rates of MISO and SPIONs were respectively 2.49 and 2.47 times higher in pH 5.5 than in pH 7.4 buffer. The mean particle size of SPION-MISOSpHLs was 950 nm. The zeta potential was -58.9 mV in pH 7.4 buffer and 36.3 mV in pH 5.5 buffer. SEM imaging showed that SPION-MISO-SpHLs had similar spherical morphologies. SPIONs were packed in the center of liposomes and were well dispersed in a TEM graph. Magnetization curve showed that SPION-MISO-SpHLs retained superparamagnetic properties. SPION-MISO-SpHLs were compared with MISO+SPION+blank liposome in hypoxia and control groups of A549 cells. MISO and SPION concentrations in culture medium showed significant differences between the same concentration groups (P < 0.0001) and at different times (P < 0.0001).

Conclusion: SPION-MISO-SpHLs possess pH-dependent release ability and superparamagnetism, and thus provides a system for targeted delivery and tracing under magnetic resonance.

Keywords: Misonidazole, pH-sensitive liposomes, superparamagnetic iron oxide nanoparticles, phenanthrolinespectrophotometry, targeting delivery, tracing system, magnetic resonance.

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Article Details

VOLUME: 16
ISSUE: 3
Year: 2019
Page: [254 - 267]
Pages: 14
DOI: 10.2174/1567201816666181114124333

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