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Glucose-Based Mesoporous Carbon Nanospheres as Functional Carriers for Oral Delivery of Amphiphobic Raloxifene: Insights into the Bioavailability Enhancement and Lymphatic Transport

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Abstract

Purpose

Oral therapy with raloxifene (RXF), an amphiphobic drug for remedy of the postmenopausal osteoporosis and estrogen-dependent breast cancer, is less effective due to its poor bioavailability (2% or so). This work aimed to devise mesoporous carbon nanospheres (MCNs) for oral delivery of RXF and evaluate their performance in bioavailability enhancement and lymphatic transport.

Methods

Glucose-based MCNs were fabricated by hydrothermal reaction followed by high-temperature activation. RXF-loaded MCNs (RXF-MCNs) were prepared by solvent-diffusion/high-pressure homogenization and stabilized by phospholipid. RXF-MCNs were fully characterized by particle size, morphology, in vitro drug release and metabolism, in vivo pharmacokinetics and lymphatic transport, and ex vivo fluorescent imaging.

Results

The prepared RXF-MCNs were 230 nm around in particle size, showing high entrapment efficiency (95.35%) and satisfactory physical stability. The oral bioavailability of RXF was enhanced by 2.07 folds through MCNs compared with RXF suspensions in rats. It was shown that reduced intestinal metabolism due to entrapment into MCNs, active transcellular uptake and increased lymphatic transport were responsible for enhanced bioavailability as a result of transport improvement.

Conclusions

The results suggest that MCNs are suitable nanocarriers for oral delivery of poorly bioavailable RXF.

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Abbreviations

BCS:

Biopharmaceutical classification system.

CLSM:

Confocal laser scanning microscopy

DSC:

Differential calorimetric scanning

EE:

Entrapment efficiency

FCNs:

Fluorescence-labeled carbon nanospheres

MCNs:

Mesoporous carbon nanospheres

MS:

Mass spectroscopy

MWCO:

Molecular weight cut-off

PDI:

Polydispersity index

QTOF:

Quadrupole time of flight

RXF:

Raloxifene

RXF-MCNs:

Raloxifene-loaded mesoporous carbon nanospheres

SEM:

Scanning electron microscopy

TEM:

Transmission electron microscope

UGT1A1:

UDP-glucuronosyltransferase 1A1

UPLC:

Ultra performance liquid chromatography

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Acknowledgments and Disclosures

This work was supported by the National Natural Science Foundation of China (No. 81402855), and the authors were also grateful for the financial assistance from the National High-tech R&D Program of China (863 Program) (No. SS2015AA020916).

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Authors and Affiliations

  1. Division of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, 510632, People’s Republic of China

    Yanghuan Ye, Tianpeng Zhang, Wan Li, Hua Sun, Danyi Lu, Baojian Wu & Xingwang Zhang

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  1. Yanghuan Ye
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  2. Tianpeng Zhang
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  3. Wan Li
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  4. Hua Sun
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Correspondence to Baojian Wu or Xingwang Zhang.

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Ye, Y., Zhang, T., Li, W. et al. Glucose-Based Mesoporous Carbon Nanospheres as Functional Carriers for Oral Delivery of Amphiphobic Raloxifene: Insights into the Bioavailability Enhancement and Lymphatic Transport. Pharm Res 33, 792–803 (2016). https://doi.org/10.1007/s11095-015-1827-7

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  • DOI: https://doi.org/10.1007/s11095-015-1827-7

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