Construction of chlorogenic acid-containing liposomes with prolonged antitumor immunity based on T cell regulation

As a potential cancer immunotherapeutic agent,chlorogenic acid(CHA)has entered phase II clinical trials in China as a lyophilized powder formulation for treating glioma.However,the in vivo instability of CHA necessitates daily intramuscular injections,resulting in patient noncompliance.In this study,CHA-phospholipid complex(PC)-containing PEGylated liposomes(CHA-PC PEG-Lipo,named as CPPL),with CHA-PC as the drug intermediate,were prepared to lower the administration frequency.CPPL demonstrated excellent physicochemical properties,enhanced tumor accumulation,and inhibited tumor growth even when the administration interval was prolonged to 4 days when compared to a CHA solution and CHA-PC loaded liposomes(CHA-PC Lipo,labeled as CPL),both of which only demonstrated antitumor efficacy with once-daily administration.Further evaluation of the in vivo antitumor immune mechanism suggested that the extended antitumor immune efficacy of CPPL could be attributed to its distinct immune-stimulating mechanism when compared with CHA solution and CPL,such as stimulating both CD4+and CD8+T cell infiltration,inhibiting myeloid-derived suppressor cell expression,reducing the expression of Th2 related factors,and notably,increasing the memory T cells in tumor tissues.This CHA-containing formulation could reduce the frequency of in vivo CHA administration during cancer treatment via T cells,especially memory T cell regulation.

Comparative study of mucoadhesive and mucus-penetrative nanoparticles based on phospholipid complex to overcome the mucus barrier for inhaled delivery of baicalein

Efficient mucosal delivery remains a major challenge for the reason of the respiratory tract mucus act as a formidable barrier to nanocarriers by trapping and clearing foreign particulates. The surface property of nanoparticles determines their retention and penetration ability within the respiratory tract mucus. However, the interaction between nanoparticles and mucus, and how these interactions impact distribution has not been extensively investigated. In this study, polymeric nanoparticles loaded with a baicalein-phospholipid complex were modified with two kinds of polymers, mucoadhesive and mucus-penetrative polymer. Systematic investigations on the physicochemical property, mucus penetration, transepithelial transport, and tissue distribution were performed to evaluate the interaction of nanoparticles with the respiratory tract. Both nanoparticles had a similar particle size and good biocompatibility, exhibited a sustained-release profile, but showed a considerable difference in zeta potential. Interestingly, mucus-penetrative nanoparticles exhibited a higher diffusion rate in mucus, deeper penetration across the mucus layer, enhanced in vitro cellular uptake, increased drug distribution in airways, and superior local distribution and bioavailability as compared to mucoadhesive nanoparticles.These results indicate the potential of mucus-penetrative nanoparticles in design of a rational delivery system to improve the efficiency of inhaled therapy by promoting mucus penetration and increasing local distribution and bioavailability.