Active targeting of dendritic cells with mannan-decorated PLGA nanoparticles

Abstract

The purpose of this study was to identify an optimum targeted particulate formulation based on mannan (MN)-decorated poly(D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs), for efficient delivery of incorporated cargo to dendritic cells (DCs). In brief, NPs were formulated from two different types of PLGA; ester-terminated (capped) or COOH-terminated (uncapped) polymer. Incorporation of MN in NPs was achieved either through addition of MN during the process of NP formation or by attachment of MN onto the surface of the freeze dried NPs by physical adsorption or chemical conjugation (to COOH terminated polymer). The formulated NPs were characterized in terms of particle size, Zeta potential and level of MN incorporation. The effect of polymer type and the incorporation method on the extent of fluorescently labelled NP uptake by murine bone marrow-derived DCs have been investigated using flowcytometry. The results of this study showed MN incorporation to enhance the uptake of PLGA NPs by DCs. Among different MN incorporation strategies, covalent attachment of MN to COOH-terminated PLGA-NPs provided the highest level of MN surface decoration on NPs. Maximum NP uptake by DCs was achieved by COOH terminated PLGA NPs containing covalent or adsorbed MN. Therefore, a better chance of success for these formulations for active targeted drug and/or vaccine delivery to DCs is anticipated.

Pulmonary dry powder vaccine of pneumococcal antigen loaded nanoparticles

“…The in vitro release data from PspA4Pro adsorbed NPs/NCMPs indicated a burst release of 40% with complete release (~94%) within 48 h. Though a high burst release was observed, this would not be a limiting factor for vaccination because any antigen released can still be taken up by DCs for processing and presentation, and that which is adsorbed onto NPs (intact) can also be taken up potentially giving an adjuvant effect as reported by Ghotbi et al, Cruz et al and others (Carrillo-Conde et al, 2011;Cruz et al, 2012;Ghotbi et al, 2011). Further, it has been established that for NPs to act as an immune potentiator or adjuvant, the attachment of NPs and antigen may not be mandatory; hence, the particles without antigen adsorbed can be taken up by DCs enhancing the immune response (Zhao et al, 2014).…”

Improved proliferation of antigen-specific cytolytic T lymphocytes using a multimodal nanovaccine

“…Based on previous observations regarding preferable uptake of nanoparticles by DCs, [34][35][36] we hypothesize that by encapsulating the antigenic components within nanoparticles, a sustained release of these components from the nanovaccines could be expected over an extended period. The advantage of this approach is that the encapsulation of vaccine components by nanotechnology is able to minimize the toxicity related to overactive immune system due to stimulation associated with vaccines delivered by a bolus dose.…”

Design and immunological evaluation of anti-CD205-tailored PLGA-based nanoparticulate cancer vaccine

“…30,32 cell viability assay DCs were seeded at a density of 10,000 cells per well in 96-well plates with complete media containing alpha MEM, 20% FBS, 5 ng/mL GM-CSF, and 1% penicillin-streptomycinamphotericin B cocktail. 33 For the assay, MTS reagent was used following the manufacturer's directions. Briefly, NP suspension was diluted in complete medium and 20 µL of each dilution containing 1 mg/mL OV was added in triplicate wells.…”