Ginsenoside modified lipid-coated perfluorocarbon nanodroplets: A novel approach to reduce complement protein adsorption and prolong in vivo circulation

Lipid-coated perfluorocarbon nanodroplets(lp-NDs)hold great promise in bio-medicine as vehicles for drug delivery,molecular imaging and vaccine agents.However,their clinical utility is restricted by limited targeted accumulation,attributed to the innate immune system(IIS),which acts as the initial defense mechanism in humans.This study aimed to optimize lp-ND formulations to mini-mize non-specific clearance by the IIS.Ginsenosides(Gs),the principal components of Panax ginseng,possessing complement inhibition ability,structural similarity to cholesterol,and comparable fat solubi-lity to phospholipids,were used as promising candidate IIS inhibitors.Two different types of ginsenoside-based Ip-NDs(Gs Ip-NDs)were created,and their efficacy in reducing IS recognition was examined.The Gs p-NDs were observed to inhibit the adsorption of C3 in the protein corona(PC)and the generation of SC5b-9.Adding Gs to Ip-NDs reduced complement adsorption and phagocytosis,resulting in a longer blood circulation time in vivo compared to lp-NDs that did not contain Gs.These results suggest that Gs can act as anti-complement and anti-phagocytosis adjuvants,potentially reducing non-specific clear-ance by the IS and improving lifespan.

Reducing systemic absorption and macrophages clearance of genistein by lipid-coated nanocrystals for pulmonary delivery

Pulmonary delivery is an effective drug delivery strategy for the treatment of local respiratory diseases.However,the rapid systemic absorption through the lung due to the thin barrier and persistent lung clearances influence the drug retention in the lung.In this study,we designed a lipid-coated genistein nanocrystals(Lipo-NCs)formulation to achieve enhanced efficiency of local pulmonary delivery.The LipoNCs were fabricated by modifying genistein nanocrystals(NCs)with phospholipid membrane through thin film hydration following the homogenization method.The prepared Lipo-NCs exhibited a decreased drug release rate compared with the naked NCs.Our results demonstrated that intracellular uptake and transcellular transport of NCs by the Calu-3 epithelial layer were reduced after lipid coating.Furthermore,the macrophages clearance was also impeded by this Lipo-NCs formulation.In vivo lung retention and distribution revealed that more genistein was retained in the lung after intratracheal administration of Lipo-NCs.The pharmacokinetic study displayed that the AUC((0-t))values of Lipo-NCs were 1.59-fold lesser than those of the NCs group,indicating a reduced systemic absorption.In conclusion,this research indicated that Lipo-NCs could be a suitable formulation for reducing systemic absorption and macrophages clearance,and thus enhancing drug concentration in lung by pulmonary delivery.

Combined flow-focus and self-assembly routes for the formation of lipid stabilized oil-shelled microbubbles

Lipid and polymer stabilized microbubbles are used in medicine as contrast agents for ultrasound imaging and are being developed for the delivery of water soluble drugs to diseased areas of the body.However,many new therapeutics exhibit poor water solubility or stability,which has led to the requirement for the development of effective hydrophobic drug delivery systems.This study presents a new method to produce microbubbles coated with an oil layer capable of encapsulating hydrophobic drugs and suitable for targeted,triggered drug release.This new method utilizes highly controllable flow-focusing microfluidics with lipid oil nanodroplets self-assembling and spreading at gas–aqueous interfaces.Oil layer inside microbubbles were produced with diameters of 2.4±0.3μm(s.d.,1.6μm)and at concentrations up to 10^(6) bubbles per milliliter.The mechanism of oil layer inside microbubble assembly and stability were characterized using methods including contact angle measurements,quartz crystal microbalance with dissipation monitoring and fluorescence resonance energy transfer imaging.