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

[ Vol. 16 , Issue. 3 ]

Author(s):

Bibo Li, Biqiang Li, Daiying He, Changyan Feng, Zhibin Luo* and Mei He*   Pages 254 - 267 ( 14 )

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.

Affiliation:

Department of Oncology and Hematology, Chongqing General Hospital, Chongqing, Department of Radiology, Chongqing General Hospital, Chongqing, P, Department of Oncology and Hematology, Chongqing General Hospital, Chongqing, Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing, Department of Oncology and Hematology, Chongqing General Hospital, Chongqing, Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing



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