Nanoemulsions Based Therapeutic Strategies: Enhancing Targeted Drug Delivery against Breast Cancer Cells

Abstract

Nanoemulsions (NEs), colloidal systems of nanoscale droplets (~100 nm), have emerged as transformative tools in oncology due to their high surface area-to-volume ratio, tunable physicochemical properties, and capacity for targeted drug delivery. While NEs find applications across diverse fields, their urgency in breast cancer therapy stems from critical limitations of conventional treatments, including systemic toxicity, poor bioavailability, and multidrug resistance. Unlike traditional chemotherapeutics, NEs enable precise tumor targeting via passive mechanisms (eg, enhanced permeability and retention effect) and active strategies (eg, ligand-functionalized surfaces), significantly reducing off-target effects. Their ability to encapsulate hydrophobic drugs, improve solubility, and sustain controlled release enhances therapeutic efficacy while overcoming resistance mechanisms prevalent in aggressive breast cancer subtypes, such as triple-negative and HER2-positive tumors. This review comprehensively analyzes NE formulation techniques (eg, ultrasonication, phase inversion temperature, bubble bursting), stability optimization through surfactant dynamics, and predictive modeling of droplet behavior. A focal point is their role in modulating tumor microenvironments, inducing apoptosis, and inhibiting angiogenesis in preclinical breast cancer models. By spotlighting NE-driven advancements in drug accumulation, reduced relapse rates, and adaptable combination therapies, this article underscores their potential to revolutionize oncology. Future research must prioritize clinical translation, scalability, and multifunctional NE designs to address unmet needs in precision breast cancer treatment.

Keywords: breast cancer therapy; nanoemulsions; nanoscale droplets; targeted drug delivery; tumor microenvironment.

Graphical abstract

Figure 1

The structural variations of NEs depend on the relative positioning of the oil and aqueous phases.

Figure 2

Different mechanisms of emulsion instability. Reprinted with permission from Shao P, Feng J, Sun P, Xiang N, Lu B, Qiu D. Recent advances in improving stability of food emulsion by plant polysaccharides. Food Res Int. 2020;137:109376. Copyright (2020), withpermission from Elsevier..

Figure 3

Protein-based emulsifiers prevent oil droplets from clumping together by using steric and electrostatic forces, which rely on the thickness, arrangement, and charge of the attached molecules. Reprinted with permission from McClements DJ, Lu J, Grossmann L. Proposed methods for testing and comparing the emulsifying properties of proteins from animal, plant, and alternative sources. Colloids Interfaces. 2022;6(2):19. © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Figure 4

Routes of drug administration and associated dosage forms. Reprinted with permission from Khan MS, Roberts MS. Challenges and innovations of drug delivery in older age. Adv Drug Delivery Rev. 2018;135:3–38. Copyright (2018), withpermission from Elsevier.

Figure 5

Challenges of oral drug delivery and technical design to overcome these challenges. Reprinted with permission from Majumdar. S. Oral drug delivery: conventional to long acting new-age designs. 2021. Copyright (2021), withpermission from Elsevier.

Figure 6

Physiological barriers to oral drug delivery. Reprinted with permission from Majumdar. S. Oral drug delivery: conventional to long acting new-age designs. 2021. Copyright (2021), withpermission from Elsevier.¹⁰⁰

Figure 7

Surface features of O/W NEs play a crucial role in medicinal applications: (A) Biomolecules enhance O/W NEs for drug delivery, immune response, viral neutralization, and targeted infection treatment. (B) Customizable surfaces enable diverse strategies, including macrophage targeting, cancer cell recognition, immune activation, and T-cell receptor presentation. Reprinted with permission from Gassmann P, List M, Schweitzer A, Sucker H. Hydrosols: alternatives for the parenteral application of poorly water soluble drugs. Eur J Pharm Biopharm. 1994;40(2):64–72. © 2021 The Authors. Published by Elsevier B.V.