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Freeze-Dried Targeted Mannosylated Selenium-Loaded Nanoliposomes: Development and Evaluation

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Abstract

The aim of this investigation was to develop and evaluate freeze-dried mannosylated liposomes for the targeted delivery of selenium. Dipalmitoylphosphatidylcholine, distearoylphosphatidylglycerol, and cholesterol were dissolved in a chloroform and methanol mixture and allowed to form a thin film within a rotatory evaporator. This thin film was hydrated with a sodium selenite (5.8 μM) solution to form multilamellar vesicles and homogenized under high pressure to yield unilamellar nanoliposomes. Se-loaded nanoliposomes were mannosylated by 0.1% w/v mannosamine (Man-Lip-Se) prior to being lyophilized. Mannosamine concentration was optimized with cellular uptake studies in M receptor expressing cells. Non-lyophilized and lyophilized Man-Lip-Se were characterized for size, zeta potential, and entrapment efficiency. The influence of liposomal composition on the characteristics of Man-Lip-Se were evaluated using acidic and basic medium for 24 h. Thermal analysis and powder X-ray diffraction were used to determine the interaction of components within the Man-Lip-Se. The size, zeta potential and entrapment efficiency of the optimum Man-Lip-Se were observed to be 158 ± 28.9 nm, 33.21 ± 0.89 mV, and 77.27 ± 2.34%, respectively. An in vitro Se release of 70–75% up to 24 h in PBS pH 6.8 and <8% Se release in acidic media (0.1 N HCl) in 1 h was observed. The Man-Lip-Se were found to withstand gastric-like environments and showed sustained release. Stable freeze-dried Man-Lip-Se were successfully formulated with a size of <200 nm, ∼75% entrapment, and achieved controlled release of Se with stability under acidic media, which may be of importance in the targeted delivery of Se to the immune system.

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Acknowledgements

We acknowledge the 2011 and 2013 Leahi Fund to Treat & Prevent Pulmonary Disease of the Hawai'i Community Foundation, Honolulu, HI, USA for research support on asthma and mesothelioma research, respectively to Dr. Mahavir B. Chougule. We would like to acknowledge the 2013 George F. Straub Trust and Robert C. Perry Fund of the Hawai'i Community Foundation, Honolulu, HI, USA for research support on lung cancer. We also acknowledge seed grant from the Research Corporation of the University of Hawai'i at Hilo, HI, USA and University of Hawaii at Hilo College of Pharmacy for providing start up financial support to our research group. We acknowledge the input of Dr. Rakesh Kumar Tekade, postdoctoral fellow, Dept. of Pharmaceutical Sciences, College of Pharmacy, University of Hawaii at Hilo, HI, USA.

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Authors and Affiliations

  1. Department of Pharmaceutical Science, College of Pharmacy, University of Hawai’i at Hilo, 34 Rainbow Drive, Hilo, Hawaii, 96720, USA

    Susanne R. Youngren, Rohit Mulik, Byoung Jun, Kenneth R. Morris & Mahavir B. Chougule

  2. Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawai’i, 651 Ilalo St, Honolulu, Hawaii, USA

    Peter R. Hoffmann

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  1. Susanne R. Youngren
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  2. Rohit Mulik
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  3. Byoung Jun
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  4. Peter R. Hoffmann
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  5. Kenneth R. Morris
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  6. Mahavir B. Chougule
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Correspondence to Mahavir B. Chougule.

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Youngren, S.R., Mulik, R., Jun, B. et al. Freeze-Dried Targeted Mannosylated Selenium-Loaded Nanoliposomes: Development and Evaluation. AAPS PharmSciTech 14, 1012–1024 (2013). https://doi.org/10.1208/s12249-013-9988-3

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