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Rifampicin Loaded Mannosylated Cationic Nanostructured Lipid Carriers for Alveolar Macrophage-specific Delivery

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Abstract

Purpose

In this study, cationic mannosylated nanostructured lipid carriers (Man-NLCs) were developed for the targeted delivery of rifampicin to alveolar macrophages.

Methods

Rifampicin loaded Man-NLCs (RFP-Man-NLCs) and rifampicin loaded unmodified nanostructured lipid carriers (REP-NLCs) were prepared using thin film homogenization method and characterized by particle size, polydispersity index, zeta potential, transmission electron microscopy, encapsulation efficiency, pharmacokinetics, biodistribution, cell specific targeting, cytotoxicity and inflammatory response.

Results

RFP-Man-NLCs and REP-NLCs obtained displayed a size distribution around 160 nm (PDI <0.30) with positive charges of approximately 30 mV. The encapsulation efficiency of RFP was above 90%. In the biodistribution study, both RFP-Man-NLCs and RFP-NLCs, compared with the commercially available rifampicin solution, displayed superior lung-targeting ability. Compared to REP-NLCs, RFP-Man-NLCs exhibited significantly higher uptake efficiency in NR8383 cells and alveolar macrophages, which achieved cell-specific targeting. In addition, RFP-Man-NLCs were demonstrated to be a safe formulation with minimum toxicity and no inflammatory response.

Conclusions

RFP-Man-NLCs provided an alternative strategy for selectively delivering rifampicin to alveolar macrophages.

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Abbreviations

AMs:

Alveolar macrophages

AUC:

Area under the curve

CLz:

Plasma clearance

Cmax :

maximum concentration

DAPI:

4′,6-diamidino-2-phenylindole

DDAB:

Dimethyldioctadecylammonium bromide

DMSO:

Dimethyl sulfoxide

EPC:

Purified ovolecithin

FITC-DHPE:

Fluorescein isothiocyanate labeled DHPE

MCT:

Medium chain triglyceride

MRT:

Mean retention time

MTT:

3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide

OCT:

Octadecylamine

PDI:

Polydispersity index

REP-NLCs:

Rifampicin loaded nanostructured lipid carriers

RFP:

Rifampicin

RFP Solution:

Rifampicin commercial solution

RFP-Man-NLCs:

Cationic mannosylated rifampicin nanostructured lipid carriers

t1/2z :

Half-life

TEM:

Transmission electron microscopy

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ACKNOWLEDGMENTS AND DISCLOSURES

This work was funded by the National S&T Major Project of China (Grant No. 2012ZX09304004001) and the National Basic Research Program of China (No. 2013CB932504). The authors report no conflicts of interest.

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Authors and Affiliations

  1. Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University, Chengdu, People’s Republic of China

    Xu Song, Qing Lin, Ling Guo, Yao Fu, Jianfeng Han, Huan Ke, Xun Sun, Tao Gong & Zhirong Zhang

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  1. Xu Song
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  2. Qing Lin
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  3. Ling Guo
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  4. Yao Fu
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  8. Tao Gong
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  9. Zhirong Zhang
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Correspondence to Tao Gong or Zhirong Zhang.

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Song, X., Lin, Q., Guo, L. et al. Rifampicin Loaded Mannosylated Cationic Nanostructured Lipid Carriers for Alveolar Macrophage-specific Delivery. Pharm Res 32, 1741–1751 (2015). https://doi.org/10.1007/s11095-014-1572-3

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  • DOI: https://doi.org/10.1007/s11095-014-1572-3

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