Recent Advances and Challenges in Controlling the Spatiotemporal Release of Combinatorial Anticancer Drugs from Nanoparticles

Abstract

To overcome cancer, various chemotherapeutic studies are in progress; among these, studies on nano-formulated combinatorial drugs (NFCDs) are being actively pursued. NFCDs function via a fusion technology that includes a drug delivery system using nanoparticles as a carrier and a combinatorial drug therapy using two or more drugs. It not only includes the advantages of these two technologies, such as ensuring stability of drugs, selectively transporting drugs to cancer cells, and synergistic effects of two or more drugs, but also has the additional benefit of enabling the spatiotemporal and controlled release of drugs. This spatial and temporal drug release from NFCDs depends on the application of nanotechnology and the composition of the combination drug. In this review, recent advances and challenges in the control of spatiotemporal drug release from NFCDs are provided. To this end, the types of combinatorial drug release for various NFCDs are classified in terms of time and space, and the detailed programming techniques used for this are described. In addition, the advantages of the time and space differences in drug release in terms of anticancer efficacy are introduced in depth.

Polymeric Nanoparticle Delivery of Combination Therapy with Synergistic Effects in Ovarian Cancer

“…Overall, polymer nanoparticles are a promising platform for co-delivery of drug combinations for ovarian cancer treatment. Advances in nanoparticle design can improve drug delivery by addressing drug resistance [ 4 , 28 , 30 , 31 , 69 , 71 ]. Specifically, sequential combination therapy with free drug formulations has been shown to improve drug efficacy and overcome resistance mechanisms.…”

“…Incorporation of the drugs into nanoparticles can improve the solubility and reduce toxicity [ 18 , 69 ]. Controlled drug release from nanoparticles could facilitate sequential drug delivery to facilitate improved control of the pharmacokinetics [ 30 , 31 , 70 ]. Thus, we review polymer-based nanoparticles (micelles, dendrimers, and solid lipid polymer-based platforms ( Figure 4 )) for simultaneous and sequential delivery of platinum- or taxane-based combinations applied to ovarian cancer with an emphasis on quantitative evaluation of nanoparticle formulation on drug synergy.…”

“…Micelles and amphiphilic (hydrophobic core/hydrophilic shell) polymer nanoparticles are advantageous for chemotherapeutic treatment because they can facilitate high drug loading, as well as controlled and stimuli-responsive drug release [ 30 , 69 ]. The formulation of polymeric micelles leverages the self-assembly of the amphiphilic polymer.…”

“… ( A ) Schematic overview of co-delivery of cisplatin and gemcitabine using polymer nanocarriers for synergistic effect (adapted with permission from [ 30 ] MDPI Open Access). ( B ) Co-formulation of cisplatin (CIS) and talazoparib (BMN) or olaparib (AZD) in lipid/polymeric nanoparticles (NPs) enhanced potency as indicated by the decrease in IC50 compared to the free drug (FD).…”

“…Another approach to improve the efficacy of drug combinations has been nanoparticle formulations [ 4 , 14 , 28 , 29 , 30 , 31 , 32 ]. Nanoscale encapsulation of chemotherapeutics such as doxorubicin increased drug efficacy and reduced cardiotoxicity compared to the conventional free drug formulation and was approved by the United States Food and Drug Administration in 1995 [ 18 ].…”