Solid Lipid Nanoparticles: Applications and Prospects in Cancer Treatment

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TL;DR

This review summarizes the role of solid lipid nanoparticles (SLNs) as nanocarriers in cancer therapy, highlighting their ability to encapsulate both hydrophilic and hydrophobic drugs, improve bioavailability, and overcome multidrug resistance. SLNs can be administered via multiple routes (topical, pulmonary, oral, parenteral, ocular) and target tumors through passive (EPR effect) and active mechanisms. The clinical significance lies in their potential to enhance therapeutic efficacy while reducing side effects, though further research on cellular-level biological responses is needed.

Full summary

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**Background:** Cancer remains a leading cause of death worldwide, and conventional chemotherapy suffers from limitations such as poor drug solubility, low specificity, high toxicity, and multidrug resistance (MDR). Solid lipid nanoparticles (SLNs), introduced in 1991, are submicron colloidal systems composed of physiological lipids dispersed in an aqueous surfactant solution. They offer advantages over traditional carriers (emulsions, liposomes, polymeric nanoparticles) including lower toxicity, larger surface area, prolonged drug release, higher cellular absorption, and improved drug solubility and bioavailability. SLNs can incorporate both hydrophilic and lipophilic drugs, are biocompatible and biodegradable, and can be produced at low cost with easy scale-up. However, they have drawbacks such as low loading efficiency and potential drug leakage due to polymorphic transitions.

**Methods:** This is a narrative review that synthesizes existing literature on SLN formulation, characterization, mechanisms of action, routes of administration, and applications in various cancers. The review covers three types of SLNs based on drug distribution: Type I (homogeneous matrix), Type II (drug-enriched shell), and Type III (drug-enriched core). Formulation techniques are briefly described (e.g., high-pressure homogenization). Delivery mechanisms include passive targeting via the enhanced permeability and retention (EPR) effect, active targeting using surface-modified ligands (e.g., hyaluronic acid, tetraiodothyroacetic acid), and codelivery strategies combining anticancer drugs with MDR inhibitors (e.g., siRNA, Hsp90 inhibitors). Antiadhesive mechanisms are also discussed. Routes of administration covered include topical, pulmonary, oral, parenteral, and ocular. Characterization parameters are mentioned but not detailed.

**Key Results:** The review presents numerous preclinical studies demonstrating SLN efficacy across cancer types: - **Breast cancer:** Paclitaxel-loaded SLNs showed high IC50 in drug-resistant MCF-7 cells, indicating potency against MDR. Curcumin-loaded SLNs increased cellular drug absorption and decreased viability in MDA-MB-231 cells. Methotrexate-loaded SLNs with ferrous functionalization enhanced cytotoxic effects in MCF-7 cells and rats. - **Lung cancer:** Naringenin-loaded SLNs improved pharmacokinetics after intratracheal administration. Paclitaxel-loaded SLNs coated with folate-PEG-chitosan lowered IC50 in M109HiFR cells and increased lung drug concentration in mice. Erlotinib-loaded SLNs showed higher cytotoxicity than free drug and adequate aerosol dispersion. - **Colon cancer:** SLNs inhibited HT-29 and GCT116 cell growth more than free fatty acid. Oxaliplatin-loaded SLNs with folic acid increased activity against HT-29 cells. 5-FU-loaded SLNs had greater anticancer activity than pure 5-FU. - **Prostate cancer:** Retinoic acid-loaded SLNs decreased viability in LNCap cells (9.53% at 200 μg/mL) with no cytotoxicity from blank SLNs. - **Liver cancer:** Sorafenib-loaded SLNs with SPIONs showed cytotoxic impact on HepG2 cells, though less than free drug. Linalool-loaded SLNs showed strong antiproliferative activity in HepG2 cells. - **Brain cancer:** Indirubin-loaded SLNs increased cytotoxicity in acidic conditions in U-87 MG cells. ApoE-coated SLNs enhanced brain accumulation. Resveratrol and andrographolide were delivered to the brain via SLNs. - **Other findings:** SLNs can be administered via multiple routes; for example, antitubercular drugs in SLNs maintained therapeutic concentrations in plasma for 8 days and organs for 10 days after oral administration. Tobramycin-loaded SLNs improved drug bioavailability in aqueous humor in rabbits.

**Clinical Implications:** SLNs represent a promising platform for cancer therapy by improving drug delivery, overcoming MDR, and enabling targeted treatment with reduced systemic toxicity. The ability to administer SLNs via various routes (especially pulmonary and oral) offers non-invasive alternatives. However, the review notes that most evidence is preclinical; clinical trials are ongoing (Table 3 mentions clinical trials but no specific results are provided). Stability issues (e.g., polymorphic transitions, burst release) remain challenges. Future research should focus on understanding cellular-level biological responses and developing surface-modified SLNs for active targeting. The review concludes that SLNs have the potential to revolutionize cancer treatment by combining drugs with nanocarriers for targeted, effective therapy with fewer side effects.