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Fabrication of TPGS-Stabilized Liposome-PLGA Hybrid Nanoparticle Via a New Modified Nanoprecipitation Approach: In Vitro and In Vivo Evaluation

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Abstract

Purpose

In this study, a new modified nanoprecipitation approach that more efficient and simpler than conventional approach was developed to synthesize D-alpha-Tocopheryl polyethylene glycol 1000 succinate stabilized liposome-PLGA hybrid nanoparticle, loaded with simvastatin (ST-TLPN).

Methods

The optimum formulation was screened via investigation of the impact of TPGS mass within polymeric core and lipid shell on the physicochemical properties of nanoparticles respectively. FTIR, and drug release of ST-TLPN were also systematically determined. Finally, the cellular internalization was evaluated using the murine macrophage cell line, in vivo pharmacokinetic behavior and antiatherogenic efficacies were elaborately examined in atherosclerotic rabbit models.

Results

With the weight ratio of TPGS-to-PLGA in organic phase of 30% and TPGS-to-lipid in aqueous phase of 35%, ST-TLPN exhibited core-shell structure, sub-100 nm size, EE% of over 90% and a slow release profile. The excellent cellular uptake was displayed in RAW264.7 cell line. Improved pharmacokinetic behavior, and enhanced antiatherogenic efficacy of ST-TLPN in the model animals were also revealed compared with ST-loaded PLGA nanoparticles.

Conclusion

These findings suggest the modified nanoprecipitation method holds great potential for fabricating LPN, aided by the multiple functions of TPGS. And the prepared TLPN is a promising delivery system for use in the pharmaceutical field.

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Abbreviations

LPHN:

Lipid–polymer hybrid nanoparticle

LPN:

Liposome-PLGA hybrid nanoparticle

PLGA:

Polylactic-co-glycolic acid

PN :

Polymeric nanoparticles

ST :

Simvastatin

ST-TLPN :

Simvastatin-loaded TLPN

TPGS :

D-alpha-Tocopheryl polyethylene glycol 1000 succinate

TLPN :

TPGS-stabilized LPN

W TPGSo /W PLGA :

The weight ratio of TPGS to PLGA in the organic phase

W TPGSw /W Lipid :

The weight ratio of TPGS to lipid in the aqueous phase

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Acknowledgements and Disclosures

The project described was financially supported by the National Natural Science Foundation of China (Grant No.81273466), Jiangsu Province Ordinary College and University Innovative Research Programs (Grant No. KYLX_0614) and the Priority Academic Program Development of Jiangsu Higher Education Institutions. The authors also wish to thank Atherosclerosis Research Centre (Nanjing Medical University, Nanjing, PR China) for the kind gift of murine macrophage cell line, and the technical support from KeyGEN BioTECH (Nanjing, Jiangsu). The authors declared no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China

    Mengyuan Zhang, Jianhua He, Wenli Zhang & Jianping Liu

  2. School of Pharmacy, Jiangsu Food & Pharmaceutical Science College, Huaian, 223005, People’s Republic of China

    Mengyuan Zhang

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Correspondence to Jianping Liu.

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Zhang, M., He, J., Zhang, W. et al. Fabrication of TPGS-Stabilized Liposome-PLGA Hybrid Nanoparticle Via a New Modified Nanoprecipitation Approach: In Vitro and In Vivo Evaluation. Pharm Res 35, 199 (2018). https://doi.org/10.1007/s11095-018-2485-3

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