Macrophage membrane-encapsulated liposomes of protopanaxadiol-type doxorubicin hydrochloride improve formulation stability for the treatment of triple-negative breast cancer.

AIMS: The use of macrophage membrane-encapsulated protopanaxadiol (PPD)-type doxorubicin hydrochloride liposomes provides an innovative solution to improve the drug stability of DOX and enhance its antitumor effect.

METHODS

PPD-type doxorubicin hydrochloride liposomes were prepared, and the preparation process of liposomes was optimized by Box-Behnken design-response surface methodology. The particle size, analytical scatter, zeta potential, encapsulation efficiency, in vitro release, and stability were also investigated. Macrophage membrane-encapsulated PPD-type doxorubicin hydrochloride liposomes (DOX-(PPD)-LIP@M) were further prepared. An in vitro cellular assay was used to detect its effect on 4T1 tumor cells, while an in vitro hemolytic assessment and an in vivo pharmacodynamic study were performed.

RESULTS

DOX-(PPD)-LIP@M was prepared by optimal prescription with average particle size (149.21 ± 1.2) nm, polydispersity coefficient (0.22 ± 0.02), potential (27.5 ± 0.12) mV, encapsulation rate, and drug loading (89.71% ±4.4%) and (7.28% ±0.8%), respectively. The prepared DOX-(PPD)-LIP@M not only prolonged the in vivo release time of the drug but also inhibited the survival of 4T1 tumor cells. The carrier synergistically enhanced the anti-tumor effect of chemotherapeutic drugs both within and outside the target area, while simultaneously attenuating cardiac pathology injury in nude mice.

CONCLUSIONS

In vitro and in vivo experiments demonstrated that DOX-(PPD)-LIP@M improves formulation stability and enhances the antitumor effect of DOX.