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Pharmaceutical Research

, 35:111 | Cite as

Functionalization of PLGA Nanoparticles with 1,3-β-glucan Enhances the Intracellular Pharmacokinetics of Rifampicin in Macrophages

  • Matshawandile Tukulula
  • Luis Gouveia
  • Paulo Paixao
  • Rose Hayeshi
  • Brendon Naicker
  • Admire Dube
Research Paper

Abstract

Purpose

Mycobacterium tuberculosis which causes tuberculosis, is primarily resident within macrophages. 1,3-β-glucan has been proposed as a ligand to target drug loaded nanoparticles (NPs) to macrophages. In this study we characterized the intracellular pharmacokinetics of the anti-tubercular drug rifampicin delivered by 1,3-β-glucan functionalized PLGA NPs (Glu-PLGA). We hypothesized that Glu-PLGA NPs would be taken up at a faster rate than PLGA NPs, and consequently deliver higher amounts of rifampicin into the macrophages.

Methods

Carbodiimide chemistry was employed to conjugate 1,3-β-glucan and rhodamine to PLGA. Rifampicin loaded PLGA and Glu-PLGA NPs as well as rhodamine functionalized PLGA and Glu-PLGA NPs were synthesized using an emulsion solvent evaporation technique. Intracellular pharmacokinetics of rifampicin and NPs were evaluated in THP-1 derived macrophages. A pharmacokinetic model was developed to describe uptake, and modelling was performed using ADAPT 5 software.

Results

The NPs increased the rate of uptake of rifampicin by a factor of 17 and 62 in case of PLGA and Glu-PLGA, respectively. Expulsion of NPs from the macrophages was also observed, which was 3 fold greater for Glu-PLGA NPs than for PLGA NPs. However, the ratio of uptake to expulsion was similar for both NPs. After 24 h, the amount of rifampicin delivered by the PLGA and Glu-PLGA NPs was similar. The NPs resulted in at least a 10-fold increase in the uptake of rifampicin.

Conclusions

Functionalization of PLGA NPs with 1,3-β-glucan resulted in faster uptake of rifampicin into macrophages. These NPs may be useful to achieve rapid intracellular eradication of Mycobacterium tuberculosis.

Key words

1,3-β-glucan nanoparticle drug delivery pharmacokinetic modelling PLGA nanoparticles rifampicin intracellular concentrations 

Abbreviations

DIEA

N,N-Diisopropylethylamine

DMF

Dimethylformamide

EDC

1-Ethyl-3(3-dimethylaminopropyl)carbodiimide hydrochloride

LC-MS

Liquid chromatography mass spectrometry

M.tb

Mycobacterium tuberculosis

NHS

N-Hydroxysuccinimide

NMR

Nuclear magnetic resonance spectroscopy

NP

Nanoparticle

PLGA

Poly(D,L-lactide-co-glycolide)

PMA

Phorbol myristate acetate

RIF

Rifampicin

TB

Tuberculosis

Notes

Acknowledgments and Disclosures

Author AD wishes to acknowledge financial support from the Council for Scientific and Industrial Research (CSIR) South Africa (YREF 2013 011) and the University of the Western Cape. This work is based on research supported in part by the National Research Foundation of South Africa (Grant Number 109059) awarded to AD.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of ChemistryTshwane University of TechnologyPretoriaSouth Africa
  2. 2.Research Institute for Medicines (iMed.ULisboa), Faculty of PharmacyUniversidade de Lisboa,LisbonPortugal
  3. 3.DST/NWU Preclinical Drug Development PlatformNorth-West University,PotchefstroomSouth Africa
  4. 4.Council for Scientific and Industrial ResearchPolymers and CompositesPretoriaSouth Africa
  5. 5.Discipline of Pharmaceutics, School of PharmacyUniversity of the Western Cape,BellvilleSouth Africa

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