Solid lipid nanoparticles in precision oncology: Mechanistic design, manufacturing innovations, and translational perspectives

Solid lipid nanoparticles (SLNs) have emerged as an adaptable nanocarrier system for cancer treatment due to
their biocompatible lipid matrix, capacity to encapsulate chemically diverse therapeutics, and ability to protect
drugs from premature degradation. Their nanoscale dimensions support passive tumor accumulation through the
enhanced permeation and retention (EPR) effect, while surface engineering allows ligand-mediated targeting to
improve cellular internalization and reduce off-target toxicity. The performance of SLNs is strongly influenced by
the manufacturing approach, as process parameters dictate particle size, polymorphic behavior, drug loading
efficiency, and release kinetics. Conventional and advanced preparation strategies including high-pressure homogenization, ultrasonication, solvent emulsification, membrane-assisted techniques, and supercritical fluid
processing continue to evolve to meet requirements for scalability, structural stability, and improved pharmacological performance. Post-processing approaches further enhance the shelf-life and handling suitability of SLN
formulations through conversion into solid dosage forms without compromising colloidal behavior after redispersion. Extensive research has demonstrated that rationally developed SLNs enhance therapeutic efficacy across
multiple cancer types, including lung, liver, colorectal, breast, prostate, cervical, melanoma, and bladder malignancies. These systems have shown improved drug solubility, superior intracellular uptake, stronger induction
of apoptosis, enhanced tumor-site accumulation, and reduced systemic toxicity compared with conventional
formulations. Co-delivery of synergistic agents, tumor-microenvironment-responsive release, and targeted surface modifications further elevate their potential as precision-oriented delivery systems. This review consolidates
advancements in SLN manufacturing technologies and evaluates their application in diverse cancer models. By
linking fabrication principles to biological performance, it highlights current opportunities and challenges in
expanding SLN-based therapeutics as promising platforms for more effective and safer cancer treatment.