Multimodal nanoparticles that provide immunomodulation and intracellular drug delivery for infectious diseases

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

“…C-PLGA NPs were synthesized using an emulsion solvent evaporation technique adopted with modifications from reference [4]. 20 mg/mL C-PLGA copolymer solution in DMF: chloroform (20:80) was added drop-wise to 10 mg/mL PVA solution in de-ionised water, under stirring at 1000 rpm.…”

“…For example, in cancer treatment, much focus is currently placed on "immuno-oncology", to develop therapies to stimulate cells of the immune system to eradicate cancerous cells [1,2]. With respect to infectious diseases, a similar approach has been proposed, as a number of infectious disease pathogens typically reside within cells of the immune system in particular, macrophages [3,4]. In this case, one strategy could be to stimulate the macrophages to self-eradicate intracellular pathogens through action of innate cellular defense mechanisms.…”

“…In this case, one strategy could be to stimulate the macrophages to self-eradicate intracellular pathogens through action of innate cellular defense mechanisms. This has important implications in treatment of diseases such as tuberculosis (TB) and human immunodeficiency virus (HIV) in which the pathogens may reside in a latent form and these cells serve as infection reservoirs [4]. Pharmaceutical scientists have made significant contributions to the development of polymeric vehicles for delivery of immune-modulatory signals to cells [5].…”

“…Pharmaceutical scientists have made significant contributions to the development of polymeric vehicles for delivery of immune-modulatory signals to cells [5]. In a previous study, an immunomodulatory nanoparticle (NP) composed of the immune modulating polysaccharide 1,3-β-glucan adsorbed onto the surface of a chitosan shell, poly( D,L -lactide-co-glycolide) (PLGA) core NP was described [4]. This NP system could significantly enhance secretion of the pro-inflammatory cytokines IL-12p70, TNF-α and INF-γ and increase generation of reactive oxygen and reactive nitrogen species (ROS/RNS) by alveolar-like macrophages compared to glucan free NPs.…”

“…Following the proof of concept of an immune modulating glucan adsorbed NP [4], we hypothesized that curdlan (a linear form of 1,3-β-glucan) could be conjugated to PLGA and…”