Curdlan-Conjugated PLGA Nanoparticles Possess Macrophage Stimulant Activity and Drug Delivery Capabilities

• Published in: Pharmaceutical research 2015-08, Vol.32 (8), p.2713-2726
• Main Authors: Tukulula, Matshawandile, Hayeshi, Rose, Fonteh, Pascaline, Meyer, Debra, Ndamase, Abongile, Madziva, Michael T., Khumalo, Vincent, Lubuschagne, Philip, Naicker, Brendon, Swai, Hulda, Dube, Admire
• Format: Article
• Language: English
• Subjects: Antitubercular Agents - administration & dosage; Antitubercular Agents - pharmacokinetics; beta-Glucans - chemistry; beta-Glucans - pharmacology; Biochemistry; Biological Transport, Active - drug effects; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Caco-2 Cells; Carbohydrate Sequence; Cell Membrane Permeability - drug effects; Cell Survival - drug effects; Chemistry, Pharmaceutical; Drug Delivery Systems; Excipients - chemistry; Humans; Immunotherapy; Intestinal Absorption; Lactic Acid - chemistry; Macrophages - drug effects; Medical Law; Molecular Sequence Data; Nanoparticles; Pharmacology/Toxicology; Pharmacy; Polyglycolic Acid - chemistry; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Research Paper; Rifampin - administration & dosage; Rifampin - pharmacokinetics; Stimulation, Chemical
• ISSN: 0724-8741; 1573-904X; 1573-904X
• DOI: 10.1007/s11095-015-1655-9

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 1 H and 13 C 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 Ca 2+ 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.