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Self-Assembled Polymersomes Conjugated with Lactoferrin as Novel Drug Carrier for Brain Delivery

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ABSTRACT

Purpose

To develop a novel brain drug delivery system based on self-assembled poly(ethyleneglycol)-poly (D,L-lactic-co-glycolic acid) (PEG-PLGA) polymersomes conjugated with lactoferrin (Lf-POS). The brain delivery properties of Lf-POS were investigated and optimized.

Method

Three formulations of Lf-POS, with different densities of lactoferrin on the surface of polymersomes, were prepared and characterized. The brain delivery properties in mice were investigated using 6-coumarin as a fluorescent probe loaded in Lf-POS (6-coumarin-Lf-POS). A neuroprotective peptide, S14G-humanin, was incorporated into Lf-POS (SHN-Lf-POS); a protective effect on the hippocampuses of rats treated by Amyloid-β25-35 was investigated by immunohistochemical analysis.

Results

The results of brain delivery in mice demonstrated that the optimized number of lactoferrin conjugated per polymersome was 101. This obtains the greatest blood–brain barrier (BBB) permeability surface area(PS) product and percentage of injected dose per gram brain (%ID/g brain). Immunohistochemistry revealed the SHN-Lf-POS had a protective effect on neurons of rats by attenuating the expression of Bax and caspase-3 positive cells. Meanwhile, the activity of choline acetyltransferase (ChAT) had been increased compared with negative controls.

Conclusion

These results suggest that lactoferrin functionalized self-assembled PEG-PLGA polymersomes could be a promising brain-targeting peptide drug delivery system via intravenous administration.

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ACKNOWLEDGMENTS & DISCLOSURES

This work was supported by National Basic Research Program of China (973 Program 2007CB935800), National Science and Technology Major Project (2009ZX09310-006), National Natural Science Foundation of China (30762544), and Postdoctoral Science Foundation of China (20060390144). The authors acknowledge Dr. Kunpeng Li, School of Life Sciences, Zhongshan University, China, for his precious help on Cryo-TEM of polymersomes.

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, The Second Military Medical University, 800 **angyin Road, Shanghai, 200433, China

    Yuan Yu

  2. Department of Pharmaceutics, School of Pharmacy,, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China

    Zhiqing Pang, Wei Lu, Qi Yin, Huile Gao & **nguo Jiang

  3. Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, P. R. 826 Zhangheng Road, Shanghai, 201203, China

    Zhiqing Pang, Wei Lu, Qi Yin, Huile Gao & **nguo Jiang

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  1. Yuan Yu
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Correspondence to **nguo Jiang.

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Yu, Y., Pang, Z., Lu, W. et al. Self-Assembled Polymersomes Conjugated with Lactoferrin as Novel Drug Carrier for Brain Delivery. Pharm Res 29, 83–96 (2012). https://doi.org/10.1007/s11095-011-0513-7

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  • DOI: https://doi.org/10.1007/s11095-011-0513-7

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