Álvaro González-Garcinuño

Locoregional breast cancer recurrence remains a significant therapeutic challenge, largely driven by limited drug selectivity and toxicity to surrounding healthy tissues. This Mini-Review examines the emerging potential of pH- and temperature-responsive formulations as injectable drug delivery systems designed to achieve preferential targeting of malignant cells. A range of advanced platforms─from smart hydrogels to hybrid constructs such as pH-sensitive liposomes embedded within thermoresponsive hydrogel matrices─are discussed, with emphasis on key design principles and synthesis strategies enabling environmental responsiveness. Among the technologies reviewed, liposome-in-hydrogel hybrid systems─still largely unexplored in breast cancer therapy─stand out for their capacity to enhance encapsulation of lipophilic therapeutics, improve formulation stability, streamline manufacturing, and provide sustained, spatially controlled drug release. Finally, critical physicochemical, mechanical, and biological characterization studies that are needed to rigorously evaluate the translational and clinical potential of these materials for the treatment of locoregional recurrent breast cancer are outlined.

Background Understanding the transport of nanoparticles within blood vessels and their distribution in tumor tissues is crucial for the successful implementation of nanotechnological strategies in clinical practice. Although numerous studies have examined nanoparticle transport in blood flow, none have comprehensively investigated all the sequential steps a nanoparticle must undergo prior to internalization by target cells. Methods A computational framework was developed in COMSOL Multiphysics to simulate nanoparticle (NP) transport from systemic administration through to tumor cell internalization. The model integrates three coupled stages: (1) NP movement within a non-Newtonian blood flow; (2) trans-endothelial transport; and (3) NP motion within the tumor stroma, incorporating affinity forces to capture ligand–receptor interactions. The tumor geometry was reconstructed, including cancer cells and fibroblasts, to reproduce physiological porosity. Multiple case studies were conducted to evaluate the impact of particle density, injection velocity, and size on NP biodistribution. Results The computational model effectively simulates nanoparticle transport across all stages. Notably, it is the first model in the literature to incorporate the affinity of functionalized nanoparticles, which facilitates ligand–receptor interactions for targeted delivery. Simulation outcomes indicate that a low Stokes number is critical for ensuring a higher percentage of particles reach the end of the capillary network. Furthermore, surface modification of nanoparticles with ligands promotes more specific distribution within the stroma, reducing the percentage of nanoparticles that fail to reach target cells by approximately 50% Conclusions A novel and comprehensive computational model has been developed to include the entire process of nanoparticle distribution following systemic administration, including specific recognition by cellular receptors.

Modeling drug release in solid tumors is a convergence point between chemical engineering and medicine. Consequently, many studies have been conducted to unravel the mechanisms behind drug distribution after administration. In addition, several approaches have been explored, ranging from pharmacokinetic and pharmacodynamic models to microscopic transport models through macroscopic transport models. This chapter focuses on the latter, macroscopic transport models, and discusses how these models can predict the processes involved in drug delivery, in free form or vehicle transported. We start by presenting some of the differentiating physiological parameters in cancer tissues and then the main equations used for modeling, including fluid flow, mass transport, and cell uptake. Also, the use of some dimensionless parameters explaining the processes that control transportation will be examined. Lastly, the final section will explore the process employed for building geometries to simulate solid tumors, as well as current research being conducted on patient-specific simulations made using medical images.

The inhaled route is regarded as one of the most promising strategies as a treatment against pulmonary infections. However, the delivery of drugs in a dry powder form remains challenging. In this work, we have used alginate to form microparticles containing an antibiotic model (colistin sulfate). The alginate microparticles were generated by atomization technique, and they were characterized by antimicrobial in vitro studies against Pseudomonas aeruginosa. Optimization of different parameters allowed us to obtain microparticles as a dry powder with a mean size (Feret diameter) of 4.45 ± 1.40 µm and drug loading of 8.5 ± 1.50%. The process developed was able to concentrate most of the colistin deposits on the surface of the microparticles, which could be observed by SEM and a Dual-Beam microscope. This produces a fast in vitro release of the drug, with a 100% release achieved in 4 h. Physicochemical characterization using the FTIR, EDX and PXRD techniques revealed information about the change that occurs from the amorphous to a crystalline form of colistin. Finally, the cytotoxicity of microparticles was tested using lung cell lines (A549 and Calu-3). Results of the study showed that alginate microparticles were able to inhibit bacterial growth while displaying non-toxicity toward lung cells.

Isoprenoids are natural compounds essential for a great number of cellular functions. One of them is farnesol (FOH), which can reduce cell proliferation, but its low solubility in aqueous solvents limits its possible clinical use as a pharmacological tool. One alternative is the use of cyclodextrins (CDs) which house hydrophobic molecules forming inclusion complexes. To assess FOH potential application in anticancer treatments, Sulfobutylated β-cyclodextrin Sodium Salt (SBE-β-CD) was selected, due to it has high solubility, approbation by the FDA, and numerous studies that ensure its safety to be administered parenterally or orally without nephrotoxicity associated. The therapeutic action of farnesol and complex were studied in different carcinoma cells, compared with a normal cell line. Farnesol showed selectivity, affecting the viability of colon and liver cancer cells more than in breast cancer cells and fibroblasts. All cells suffered apoptosis after being treated with 150 μM of free FOH, but the complex reduced their cell viability between 50 and 75%. Similar results were obtained for both types of isomers, and the addition of phosphatidylcholine reverses this effect. Finally, cell cycle analysis corroborates the action of FOH as inducer of a G0/G1 phase; when the cells were treated using the complex form, this viability was reduced, reaching 50% in the case of colon and liver, 60% in fibroblasts, and only 75% in breast cancer.