Curdlan-Conjugated PLGA Nanoparticles Possess Macrophage Stimulant Activity and Drug Delivery Capabilities.
OBJECTIVE
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.
Encapsulation and Delivery Group, Council for Scientific and Industrial Research, 1 Meiring Naude Road, Brummeria, Pretoria, 0001, South Africa.
Matshawandile
M
Tukulula
Rose
R
Hayeshi
Pascaline
P
Fonteh
Debra
D
Meyer
Abongile
A
Ndamase
Michael T
MT
Madziva
Vincent
V
Khumalo
Philip
P
Labuschagne
Philip
P
Lubuschagne
Brendon
B
Naicker
Hulda
H
Swai
Admire
A
Dube
D000995:Antitubercular Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001693:Biological Transport, Active / Q000187:drug effects; D018938:Caco-2 Cells; D002240:Carbohydrate Sequence; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry*; D006801:Humans; D007408:Intestinal Absorption; D019344:Lactic Acid / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects*; D008969:Molecular Sequence Data; D053758:Nanoparticles; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012293:Rifampin / Q000008:administration & dosage / Q000493:pharmacokinetics; D013268:Stimulation, Chemical; D047071:beta-Glucans / Q000737:chemistry* / Q000494:pharmacology*
D000995:Antitubercular Agents; D005079:Excipients; D047071:beta-Glucans; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C038459:curdlan; D012293:Rifampin