Synthesis of Carrier-Free Paclitaxel–Curcumin Nanoparticles: The Role of Curcuminoids

Abstract

The systemic administration of paclitaxel (PTX)-based combinatorial therapies is significantly restricted due to the multidrug resistance. Curcumin (CUR) not only inhibits cancer-cell proliferation but also reverses the PTX resistance. However, achieving codelivery of these two drugs is a challenge due to their poor water solubility. Herein, we synthesized carrier-free PTX NPs by a facile nanoprecipitation method with the help of CUR and other curcuminoids present in turmeric extract. The prepared NPs demonstrated spherical morphologies with high conformational stability. Experimental studies showed that the presence of both bisdemethoxycurcumin and demethoxycurcumin is essential for the successful formation of spherical and monodisperse NPs. Computational studies revealed that the presence of the more sterically available curcuminoids BMC and DMC makes the self-assembly procedure more adaptable with a higher number of potential conformations that could give rise to more monodisperse PTX-CUR NPs. Compared with PTX alone, PTX-CUR NPs have shown comparable therapeutic efficiency in vitro and demonstrated a higher cellular internalization, highlighting their potential for in vivo applications. The successful formation of PTX-CUR NPs and the understanding of how multiple drugs behave at the molecular level also provide guidance for developing formulations for the synthesis of high-quality and effective carrier-free nanosystems for biomedical applications.

Chitosan-Based Nano-Smart Drug Delivery System in Breast Cancer Therapy

“…The big challenges in the development of anticancer drugs are: Anticancer drugs are generally hydrophobic. Small-molecule hydrophobic drugs can be quickly removed from the tumor site [ 94 , 95 ]. Poor solubility makes it difficult to dissolve and release the drug from the tumor [ 94 , 95 ].…”

“…Small-molecule hydrophobic drugs can be quickly removed from the tumor site [ 94 , 95 ]. Poor solubility makes it difficult to dissolve and release the drug from the tumor [ 94 , 95 ]. They have a lower half-life and subtherapeutic tumor concentrations.…”

“…Anticancer drugs are generally hydrophobic. Small-molecule hydrophobic drugs can be quickly removed from the tumor site [ 94 , 95 ].…”

Carrier-free chemo-phototherapeutic nanomedicines with endo/lysosomal escape function enhance the therapeutic effect of drug molecules in tumors

“…16 Compared with conventional nanomedicines using organic and inorganic nanomaterials as drug carriers to deliver drugs, carrier-free nanomedicines offer advantages of extremely high drug loading capacity (480%), minimal nondrug constituent burden, and facile preparation processes. [17][18][19][20][21][22] Therefore, herein, we aim to demonstrate using MPN coating to facilitate carrier-free nanomedicine's endo/lysosomal escape and further improve their therapeutic efficacy. We designed to combine Cur and ICG as carrier-free nanomedicines (ICG-Cur NPs) for potential synergistic chemotherapy and photothermal/photodynamic therapy.…”