Curdlan-conjugated PLGA nanoparticles possess macrophage stimulant activity and drug delivery capabilities

Loading...
Thumbnail Image

Authors

Tukulula, Matshawandile
Hayeshi, Rose
Fonteh, Pascaline Nanga
Meyer, Debra
Ndamase, Abongile
Madziva, Michael Taurai
Khumalo, Vincent
Lubuschagne, Philip
Naicker, Brendon
Swai, H.

Journal Title

Journal ISSN

Volume Title

Publisher

Springer

Abstract

PURPOSE : There is significant interest in the application of nanoparticles to deliver immunostimulatory signals to cells. We hypothesized that curdlan (immune stimulating polymer) could be conjugated to PLGA and nanoparticles from this copolymer would possess immunostimulatory activity, be non-cytotoxic and function as an effective sustained drug release system. METHODS : Carbodiimide chemistry was employed to conjugate curdlan to PLGA. The conjugate (C-PLGA) was characterized using 1H and 13C NMR, FTIR, DSC and TGA. Nanoparticles were synthesized using an emulsion-solvent evaporation technique. Immunostimulatory activity was characterized in THP-1 derived macrophages. MTT assay and real-time impedance measurements were used to characterize polymer and nanoparticle toxicity and uptake in macrophages. Drug delivery capability was assessed across Caco-2 cells using rifampicin as a model drug. RESULTS : Spectral characterization confirmed successful synthesis of C-PLGA. C-PLGA nanoparticles enhanced phosphorylated ERK production in macrophages indicating cell stimulation. Nanoparticles provided slow release of rifampicin across Caco-2 cells. Polymers but not nanoparticles altered the adhesion profiles of the macrophages. Impedance measurements suggested Ca2+ dependent uptake of nanoparticles by the macrophages. CONCLUSIONS : PLGA nanoparticles with macrophage stimulating and sustained drug delivery capabilities have been prepared. These nanoparticles can be used to stimulate macrophages and concurrently deliver drug in infectious disease therapy.

Description

Keywords

Immunostimulant nanoparticles, Curdlan, PLGA nanoparticles, Real-time impedance measurements, Rifampicin

Sustainable Development Goals

Citation

Tukulula, M, Hayeshi, R, Fonteh, P, Meyer, D, Ndamase, A, Madziva, MT, Khumalo, V, Lubuschagne, P, Naicker, B, Swai, H & Dube, A 2015, 'Curdlan-conjugated PLGA nanoparticles possess macrophage stimulant activity and drug delivery capabilities', Pharmaceutical Research, vol. 32, no. 8, pp. 2713-2726.