Recent advances in "smart" delivery systems for extended drug release in cancer therapy

Abstract

Advances in nanomedicine have become indispensable for targeted drug delivery, early detection, and increasingly personalized approaches to cancer treatment. Nanoparticle-based drug-delivery systems have overcome some of the limitations associated with traditional cancer-therapy administration, such as reduced drug solubility, chemoresistance, systemic toxicity, narrow therapeutic indices, and poor oral bioavailability. Advances in the field of nanomedicine include "smart" drug delivery, or multiple levels of targeting, and extended-release drug-delivery systems that provide additional methods of overcoming these limitations. More recently, the idea of combining smart drug delivery with extended-release has emerged in hopes of developing highly efficient nanoparticles with improved delivery, bioavailability, and safety profiles. Although functionalized and extended-release drug-delivery systems have been studied extensively, there remain gaps in the literature concerning their application in cancer treatment. We aim to provide an overview of smart and extended-release drug-delivery systems for the delivery of cancer therapies, as well as to introduce innovative advancements in nanoparticle design incorporating these principles. With the growing need for increasingly personalized medicine in cancer treatment, smart extended-release nanoparticles have the potential to enhance chemotherapy delivery, patient adherence, and treatment outcomes in cancer patients.

Keywords: extended drug release; nanomedicine; personalized medicine; smart delivery systems.

Figure 1

Multifunctional targeting employed by “smart” nanoparticles. Note: Smart nanoparticles employ passive- targeting, active- targeting, and stimuli-responsive targeting methods. Abbreviations: EPR, enhanced permeability and retention; mAb, monoclonal antibody.

Figure 2

Physiological benefits of “smart” and extended-release nanopolymers. Note: Smart and extended-release nanopolymers each confer physiological benefits, with some being characteristic of both nanoparticle types.

Figure 3

A pH-responsive, “smart” active polymer-delivery system. Notes: Yellow spheres represent folic acid molecules, green represents hydrophobic drugs, blue shows the hydrophilic part of the polymer, and gray is the hydrophobic part of the polymer. Reprinted from Biophys Chem, 214–215, Li X, Mctaggart M, Malardier-Jugroot C, Synthesis and characterization of a pH responsive folic acid functionalized polymeric drug delivery system, 17–26, copyright 2016, with permission from Elsevier.

Figure 4

Clinical benefits of “smart” and extended-release NPs. Note: Smart and extended-release nanopolymers each confer clinical benefits, with some being characteristic of both nanoparticle types.

Figure 5

(A) RAGxCγ double-mutant mice bearing heterotopic xenografts of pancreatic PANC1 tumors. (B) Extended release of OP from PLGA-OP surgical implants, measurement of tumor volumes days post implantation, tumor weights at necropsy, and number of liver metastatic clusters. Note: Copyright © 2015. Dove Medical Press. Reproduced from Hrynyk M, Ellis JP, Haxho F, et al. Therapeutic designed poly (lactic-co-glycolic acid) cylindrical oseltamivir phosphate-loaded implants impede tumor neovascularization, growth and metastasis in mouse model of human pancreatic carcinoma. Drug Des Devel Ther. 2015;9: 4573–4586. Abbreviations: OP, oseltamivir phosphate; PLGA, poly(lactic-co-glycolic acid).