Drug Delivery Systems for Localized Cancer Combination Therapy

Abstract

With over 2 million cancer cases and over 600,000 cancer-associated deaths predicted in the U.S. for 2022, this life-debilitating disease continuously impacts the lives of people across the nation every day. Therapeutic treatment options for cancer have historically involved chemotherapies to eradicate tumors with cytotoxic mechanisms which can negatively affect the efficacy versus toxicity ratio of treatment. With a need for more directed and therapeutically active options, targeted small-molecule inhibitors and immunotherapies have since emerged to mitigate treatment-associated toxicities. However, aggressive tumors can employ a wide range of defense mechanisms to evade monotherapy treatment altogether, resulting in the recurrence of therapeutically resistant tumors. Therefore, many clinical routines have included combination therapy in which anticancer agents are combined to provide a synergistic attack on tumors. Even with this approach, maximizing the efficacy of cancer treatment is contingent upon the dose of drug that reaches the site of the tumor, so often therapy is administered at the site of a tumor via localized delivery platforms. Commonly used platforms for localized drug delivery include polymeric wafers, nanofibrous scaffolds, and hydrogels where drug combinations can be loaded and delivered synchronously. Attaining synergistic activity from these localized systems is dependent on proper material selection and fabrication methods. Herein, we describe these important considerations for enhancing the efficacy of cancer combination therapy through biodegradable, localized delivery systems.

Hydrogels as local depots for on-demand therapeutic delivery: potential therapeutic approaches for tumor metastasis

“…68,69 Maximizing the efficacy of the treatment depends on the dose of drug that reaches the target site, so therapy is carried out at the target site through localized delivery platforms. 70 Local delivery systems have the ability to deliver high doses of therapeutic molecules at the target site and provide controlled and sustained drug molecule release with minimized nonspecific distribution of therapeutics in healthy tissues. 71,72 Hydrogel-based local drug delivery system is one of the long-acting drug delivery formulations that allow controlled drug release over days, weeks, months, and years after single-dose administration and a stable pharmacokinetic profile.…”

“…Hydrogels are attractive for the controlled delivery of therapeutic agents such as chemotherapeutic drugs, immunosuppressive agents, antibodies, vaccines, cytokines, and immune cells. 70 Despite the interesting properties of hydrogels in drug delivery systems, some limitations still exist (Table 2). Because they are soft, hydrophilic, and wet materials, hydrogels are limited to encapsulating hydrophobic drugs and have relatively low tensile strengths.…”

The Current Status, Challenges, and Future Potential of Therapeutic Vaccination in Glioblastoma

“…The method of vaccine delivery is also a consideration in the development of cancer therapeutic vaccines [100][101][102]. The vast majority of vaccination trials in glioblastomas utilize subcutaneous, intradermal, or intravenous delivery methods (Table 1).…”

“…However, there is increasing interest in novel drug delivery methods that may improve efficacy. Some examples of local delivery include the following: polymeric wafers, nanofibrous scaffolds, and hydrogels [100][101][102]. While out of the scope of the present review, recent articles extensively review advances in drug delivery that may be incorporated into vaccine development for GBM [100][101][102].…”

The improving strategies and applications of nanotechnology-based drugs in hepatocellular carcinoma treatment

“…For example, PROVENGE, an immune cell-based vaccine, has been approved by the US FDA to treat hormone-refractory prostate cancer ( Cheever and Higano, 2011 ). Studies have shown that storage conditions, formulation, stability in vivo , targeting, blood concentration, target concentration and other factors are important factors affecting the therapeutic effect of drugs ( Vitharana et al, 2023 ; Woodring et al, 2023 ). In the process of new drug research exploration, researchers have conducted more investigations for these factors and made great progress.…”