Self-microemulsifying drug delivery system for improving the bioavailability of huperzine A by lymphatic uptake

Huperzine A(Hup-A) is a poorly water-soluble drug with low oral bioavailability. A selfmicroemulsifying drug delivery system(SMEDDS) was used to enhance the oral bioavailability and lymphatic uptake and transport of Hup-A. A single-pass intestinal perfusion(SPIP) technique and a chylomicron flow-blocking approach were used to study its intestinal absorption, mesenteric lymph node distribution and intestinal lymphatic uptake. The value of the area under the plasma concentration–time curve(AUC) of Hup-A SMEDDS was significantly higher than that of a Hup-A suspension(P <0.01).The absorption rate constant(K_a) and the apparent permeability coefficient(P_(app)) for Hup-A in different parts of the intestine suggested a passive transport mechanism, and the values of K_a and P_(app) of Hup-A SMEDDS in the ileum were much higher than those in other intestinal segments. The determination of Hup-A concentration in mesenteric lymph nodes can be used to explain the intestinal lymphatic absorption of Hup-A SMEDDS. For Hup-A SMEDDS, the values of AUC and maximum plasma concentration(C_(max)) of the blocking model were significantly lower than those of the control model(P<0.05). The proportion of lymphatic transport of Hup-A SMEDDS and Hup-A suspension were about 40% and 5%,respectively, suggesting that SMEDDS can significantly improve the intestinal lymphatic uptake and transport of Hup-A.

Recent advances in diverse nanosystems for nitric oxide delivery in cancer therapy

Gas therapy has been proven to be a promising and advantageous treatment option for cancers.Studies have shown that nitric oxide(NO)is one of the smallest structurally significant gas molecules with great potential to suppress cancer.However,there is controversy and concern about its use as it exhibits the opposite physiological effects based on its levels in the tumor.Therefore,the anti-cancer mechanism of NO is the key to cancer treatment,and rationally designed NO delivery systems are crucial to the success of NO biomedical applications.This review summarizes the endogenous production of NO,its physiological mechanisms of action,the application of NO in cancer treatment,and nano-delivery systems for delivering NO donors.Moreover,it briefly reviews challenges in delivering NO from different nanoparticles and the issues associated with its combination treatment strategies.The advantages and challenges of various NO delivery platforms are recapitulated for possible transformation into clinical applications.

A facile phototheranostic nanoplatform integrating NIR-Ⅱ fluorescence/PA bimodal imaging and image-guided surgery/PTT combinational therapy for improved antitumor efcacy

Phototheranostic with highly integrated functions is an attractive platform for cancer management. It remains challenging to develop a facile phototheranostic platform with complementary bimodal imaging and combinational therapy capacity. Herein, the small-molecule cyanine IR780 loaded liposomes have been harnessed as a nanoplatform to simultaneously realize photoacoustic(PA)/the second near-infrared window(NIR-Ⅱ) fluorescence imaging and image-guided surgery/adjuvant photothermal therapy(PTT).This nanoplatform exhibits attractive properties like uniform controllable size, stable dispersibility, NIR-Ⅱ fluorescence emission, photothermal conversion, and biocompatibility. Benefiting from the complementary PA/NIR-Ⅱ fluorescence bimodal imaging, this nanoplatform was successfully applied in precise vasculature delineation and tumor diagnosis. Interestingly, the tumor was clearly detected by NIR-Ⅱ fluorescence imaging with the highest tumor-to-normal-tissue ratio up to 12.69, while signal interference from the liver was significantly reduced, due to the difference in the elimination rate of the nanoplatform in the liver and tumor. Under the precise guidance of the image, the tumor was accurately resected, and the simulated residual lesion after surgery was completely ablated by adjuvant PTT. This combined therapy showed improved antitumor efcacy over the individual surgery or PTT. This work develops a facile phototheranostic nanoplatform with great significance in accurately diagnosing and effectively treating tumors using simple NIR light irradiation.

Multifunctional building elements for the construction of peptide drug conjugates

Engineering of smart building molecules is key basis in designing intelligent drug delivery systems.As an emerging sophisticated delivery system strategy,the powerful functions of peptide drug conjugates(PDCs)are attributed to a smart linker and multifunctional peptide domain.Peptides exhibit a wide range of functions and properties,including easy chemical synthesis and versatile modification,tunable biocompatibility,diversified self-assembled nanostructures,specific recognition/binding,and deep penetration of the cell membrane/extracellular matrix.In addition,various types of linkers enable PDCs to release drugs responsively according to the disease microen-vironment or treatment needs.Owing to these inherent advantages,PDCs have been widely explored for drug delivery.Herein,the latest developments in functional peptides and linkers commonly used to construct smart PDCs are reviewed.The purpose is to bring widespread attention to PDC design strategies and their contribution to fighting various diseases,as well as to provide guidance for research on intelligent PDC drug delivery systems.