Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive cartilage and bone destruction. Activated macrophages that overexpress folic acid (FA) receptors play an important role in RA, due to their abundance in inflamed synovial membrane and joints. In an effort to deliver drugs to the inflamed tissues, multifunctional FA receptor-targeting and pH-responsive nanocarriers were developed. They were composed of lipids, polyethylene glycol (PEG)–poly(lactic-
co
-glycolic acid) (PLGA) forming a hydrophilic shell, FA around the hydrophilic shell as a targeting ligand, and poly(cyclohexane-1,4-diylacetone dimethylene ketal) (PCADK) and PLGA as a hydrophobic core. PCADK also acts as a pH-responsive material. Methotrexate (Mtx) was encapsulated in the nanoparticles, which exhibited pH-responsive release in vitro. Cellular uptake and cytotoxicity experiments revealed that FA-PEG-PLGA/PCADK–lipid nanoparticles loaded with Mtx (FA-PPLNPs) exhibited superior cellular uptake and higher cytotoxicity to activated macrophages than PPLNPs/Mtx. The therapeutic effect of FA-PPLNPs/Mtx in RA was confirmed in an adjuvant-induced arthritis rat model. These results suggest that the multifunctional folate receptor-targeting and pH-responsive nanocarriers are promising for the treatment of RA.
Activated macrophages play a vital role in rheumatoid arthritis (RA) pathophysiology. CD44 is an overexpressed receptor on activated macrophages that is a potential target site for RA treatment. In this study, we prepared hyaluronic acid (HA) coated acid-sensitive polymeric nanoparticles (HAPNPs) composed of egg phosphatidylcholine, polyethylenimine, and poly (cyclohexane-1,4-diyl acetone dimethylene ketal) (PCADK) loaded with dexamethasone (Dex) for the treatment of RA. PCADK was used to form polymeric cores because of its acid-sensitivity. The HAPNPs were about 150 nm in size and had a zeta potential of −2.84 mV. The release rate of Dex from HAPNPs/Dex in vitro increased markedly when the pH decreased from 7.4 to 4.5, indicating that the HAPNPs were pH-sensitive. In a cellular uptake study, stronger fluorescence signals were observed in activated macrophages treated with HAPNPs, suggesting that HAPNPs could be effective nanodevices target to activated macrophages. In rats with adjuvant-induced arthritis, HAPNPs could inhibited the progression of RA. Taken together, these results suggest that the HAPNPs could be useful in RA therapy.
We demonstrate an ew approach to pattern functional organic molecules with atemplate of foams,and achieve ar esolution of sub 100 nm. The bubble-assisted assembly (BAA) process is consisted of two periods,i ncluding bubble evolution and molecular assembly,which are dominated by the Laplace pressure and molecular interactions,r espectively. Using TPPS (meso-tetra(4-sulfonatophenyl) porphyrin), we systematically investigate the patterns and assembly behaviour in the bubble system with as eries of characterizations,w hich show good uniformity in nanoscale resolution. Theoretical simulations reveal that TPPSsJ -aggregates contribute to the ordered construction of molecular patterns.F inally,w ep ropose an empirical rule for molecular patterning approach, that the surfactant and functional molecules should have the same type of charge in at wo-component system. This approach exhibits promising feasibility to assemble molecular patterns at nanoscale resolution for micro/nano functional devices.
A series of polyethylenimines-coated poly(d,l-lactide-co-glycolide)/lipid nanoparticles (PPLs) were fabricated for delivering paclitaxel via a simple nano-precipitation method. Four kinds of polyethylenimines (PEIs) (800 Da-, 2000 Da- and 25 kDa-branched PEIs, and 25 kDa-linear PEI) were selected as a polymeric coating for the nanoparticles. The PPLs were evaluated for their cytotoxic effects towards tumor cells. The nanoparticles were uniform spheres with particle sizes ranging from 135.8 to 535.9 nm and zeta potentials between 13.5 and 45.4 mV. The content of lipids and PEIs were optimized at lipids content from 0 to 40% and PEI content from 2.5% to 10%, respectively. At 20% lipid content and 5% PEI content, the formulation was found to be optimal. In vitro experiments showed that 25 kDa-branched PEI coated PLGA/lipid nanoparticles (25k-bPPLs) had higher cytotoxicity than other PPLs in several cancer cell lines. Meanwhile, 25k-bPPLs maintained high cellular delivery efficiency without excessive toxicity, which was confirmed by confocal microscopy and flow cytometry analyses. Furthermore, 25k-bPPLs displayed excellent colloidal stability in pH 7.4 PBS. In conclusion, 25k-bPPLs are promising drug delivery vehicles for cancer therapeutics.
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