Ismail, J.; Klepsch, L.C.; Dahlke, P.; Tsarenko, E.; Vollrath, A.; Pretzel, D.; Jordan, P.M.; Rezaei, K.; Czaplewska, J.A.; Stumpf, S.; Beringer-Siemers, B.; Nischang, I.; Hoeppener, S.; Werz, O.; Schubert, U.S.: PEG-Lipid-PLGA Hybrid Particles for Targeted Delivery of Anti-Inflammatory Drugs. Pharmaceutics 16 (2024), p. 187/1-24
10.3390/pharmaceutics16020187
Open Access Version
Abstract:
Hybrid nanoparticles (HNPs) were designed by combining a PLGA core with a lipid shell that incorporated PEG-Lipid conjugates with various functionalities (-RGD, -cRGD, -NH2, and -COOH) to create targeted drug delivery systems. Loaded with a neutral lipid orange dye, the HNPs were extensively characterized using various techniques and investigated for their uptake in human monocyte-derived macrophages (MDMs) using FC and CLSM. Moreover, the best-performing HNPs (i.e., HNP-COOH and HNP-RGD as well as HNP-RGD/COOH mixed) were loaded with the anti-inflammatory drug BRP-201 and prepared in two size ranges (d(H) similar to 140 nm and dH similar to 250 nm). The HNPs were examined further for their stability, degradation, MDM uptake, and drug delivery efficiency by studying the inhibition of 5-lipoxygenase (5-LOX) product formation, whereby HNP-COOH and HNP-RGD both exhibited superior uptake, and the HNP-COOH/RGD (2:1) displayed the highest inhibition.