Applications of Solid Lipid Nanoparticles in Cancer: History
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Contributor:
Durgaramani Sivadasan
,
Kalaivanan Ramakrishnan
,
Janani Mahendran
,
Hariprasad Ranganathan
,
Arjunan Karuppaiah
,
Habibur Rahman

Cancer is recognized as one of the world’s most deadly diseases in its different forms. In the field of nanotechnology, solid lipid nanoparticles (SLNs) play a vital role with a wide range of diverse applications, namely drug delivery, clinical medicine, and cancer therapeutics. SLNs establish a significant role owing to their ability to encapsulate hydrophilic and hydrophobic compounds, biocompatibility, ease of surface modification, scale-up feasibility, and possibilities of both active and passive targeting to various organs. In cancer therapy, SLNs have emerged as imminent nanocarriers for overcoming physiological barriers and multidrug resistance pathways.

  • cancer
  • drug delivery
  • lipid

1. Introduction

Cancer is recognized as one of the world’s most deadly diseases in its different forms. The capacity of treatments to reach specific intracellular and intercellular targets while reducing their accumulation at nonspecific areas is critical to treat cancer. Chemotherapy performed via conventional drug administration is the most comprehensive cancer treatment, but it has a number of drawbacks such as lower drug solubility and specificity, lower therapeutic index, and increased toxicity. The resistance of malignant cells to chemotherapy drugs is another hurdle in the way of treatment, and it is recognized as multidrug resistance (MDR), causing resistance to a wide range of medications [1]. Solid lipid nanoparticles (SLNs) have evolved as a potential nanodelivery system (nanocarriers) in cancer treatment. The colloidal carriers such as emulsions, liposomes, and polymeric micro and nanoparticles were apparently replaced by the development of SLNs (1991) [2]. SLNs are submicron colloidal systems that contain physiological lipids dispersed in an aqueous surfactant solution or water but remain solid in the body environment. When compared to traditional colloidal carriers, SLNs have lower toxicity, a larger surface area, prolonged drug release, higher cellular absorption, and the ability to improve drug solubility and bioavailability [3]. The matrix type and the drug’s position determine the drug release of the formulation. SLNs composed of biodegradable and biocompatible (e.g., physiological lipids or lipid molecules) materials may incorporate both hydrophilic and lipophilic bioactives and act as a potential choice for a targeted drug delivery system [4]. The drug is dispersed or dissolved in the hydrophobic solid core, which has a monolayer phospholipid coating. The particle size after drug encapsulation ranges from nanoscale to submicron scale (50–1000 nm); the synthesis of nanoparticles does not require the use of organic solvents, and the process (e.g., high-pressure homogenization) may be accomplished at reduced cost and easily scaled up [5]. 

2. Breast Cancer

Breast carcinoma is the most common malignancy in women, and its rate of incidence is rising gradually over time. Insufficient drug concentrations approaching the carcinoma, prompt excretion, systemic toxicity, and side effects are all significant impediments to effective breast cancer chemotherapies. SLNs in the treatment of breast cancer have the potential to overcome prevailing chemotherapeutic restrictions, as well as the issues related to conventional chemotherapy and MDR [6]. Chemoresistance or MDR can be induced by either one or two mechanisms: physical impairment of drug delivery to the tumor site (e.g., poor absorption, enhanced metabolism/excretion, and/or impaired drug diffusion into the tumor mass)and intracellular mechanisms which elevate apoptosis. SLNs are effective in targeting tumor vehicles because of the EPR effect’s passive targeting characteristics. Paclitaxel (PAX)-loaded SLNs were investigated, and it was shown that the modified SLNs were stable and reproducible [7]. The dimethyl sulfoxide solubilization Cremophor EL vehicles were studied for effectiveness against MCF-7 drug-resistant and drug-sensitive cells, and SLNs loaded with paclitaxel were targeted against drug-resistant breast cancer cells. High IC50 concentration was reported in drug-resistant cells, according to a study on concentration-dependent cytotoxicity and enhanced cellular uptake, particularly in drug-resistant cells, indicating their potency in evading multidrug resistance pathways in breast cancer cells [3]. SLNs incorporated with curcumin present increased cellular drug absorption capacity, and the use of curcumin carriers to combat MDA-MB-231 (breast cancer cell line) shows their potency against cancer and a decrease in cell viability and an elevation in apoptotic cells when compared to dimethyl sulfoxide-diluted curcumin [8]. Methotrexate-loaded SLNs were ferrous-functionalized to achieve active tumor targeting, resulting in an enhanced cytotoxic effect in MCF-7 breast cancer cells and in rats with induced breast cancer; they showed enhanced drug concentration in tumor sites and improved anticancer activity [9].

3. Lung Cancer

Lung cancer (LuC) is the most frequently diagnosed cancer in both men and women and is the main cause of cancer-related death worldwide. Despite the fact that chemotherapy and radiation are effective in treating lung cancer, a vast proportion of patients develop a relapse of the illness that is more resistant to subsequent treatment. As a result, in order to enhance the prognosis of this kind of cancer, a novel therapeutic strategy is required. A study of SLNs loaded with anticancer compound naringenin reported an increased cellular uptake pattern following intratracheal administration of naringenin-loaded SLNs in rats according to the drug’s pharmacokinetic properties, such as mean residence time and maximum plasma concentration.SLNs can be administrated through the lungs by inhalation, and paclitaxel loaded into SLNs coated with a polymer composed of folate-poly (ethylene glycol) and chitosan lowered the IC50 value in vitro against M109HiFR lung cancer cells and increased drug concentration in the lungs of healthy and sick mice [10]. A study of SLNs incorporated with erlotinib indicated that the free drug exhibited a lower cytotoxic effect than the drug encapsulated in SLNs, and the system exhibited adequate aerosol dispersion capability, indicating that it could be exploited for pulmonary delivery [11].

4. Colon Tumor

SLNs have the potential to be an effective treatment for colon cancers. SLNs were found to inhibit cell growth more than free fatty acid in HT-29 and GCT116 adenocarcinoma cells by increased apoptotic activation [12]. Oxaliplatin incorporated in SLNs with folic acid resulted in increased chemotherapeutic activity against the HT-29cell line compared to the free drug and non-functionalized SLNs [13]. For the treatment of CRC, SLNs containing 5-fluorouracil (5-FU) have greater anticancer activity than pure 5-FU [14].

5. Prostate Cancer

There has been an increase in the incidence of prostate cancer due to the inability to target therapies to neoplastic cells, and SLNs are reported to be effective at inhibiting prostate cancer cells (e.g., LNCap) as a drug delivery system. Studies indicate that adjusting the process parameters (e.g., pressure/temperature) and using different lipids increase the anticancer activityof SLNs loaded withretinoic acid (RTA); RTA-SLNs incubated in LNCap cell lines exhibited decreased cell viability and higher drug concentrations (e.g., 9.53% at 200 g/mL), but blank SLNs exhibited no cytotoxicity [15].

6. Liver Cancer

Liver cancer causes a significant amount of mortality, and treatments for liver cancer (LivC) are frequently restricted by poor drug physicochemical characteristics. Chemotherapy and targeted medicines such assorafenib have just a minimal effect on patient survival. Furthermore, radiation is unsuccessful in most cases, requiring the development of alternative therapeutic approaches. SPIONs were added to HepG2 cell line human hepatocyte carcinoma, and sorafenib-loaded SLNs exhibited a significant cytotoxic impact, although they were not as effective as the free drug. However, cellular absorption of SLNs and magnetic targeting tests demonstrated improved hepatocellular carcinoma therapy [16]. The use of linalool SLNs loaded with different formulations against HepG2 cell line human hepatocyte carcinoma and A549 lung adenocarcinoma reporter gene cell lines was studied;they showed strong antiproliferative activity inthe HepG2 human hepatocellular carcinoma cell line [17].

7. Brain Cancer

The use of SLNs is an effective nanoscale lipid-based approach for brain cancer drug delivery. The specific process of the delivery system passing through the BBB is unclear; it is thought that internalization is facilitated by endothelial cells (pinocytosis). The procedure of endocytosis/pinocytosis leads to the effective absorption of circulating plasma proteins onto the SLN surface [18]. SLNs incorporated with the drug indirubin showed an increased cytotoxic effect in acidic conditions in U-87 MG human cell line [19]. SLNs coated with apolipoprotein E (ApoE)showed active cellular uptake and increased accumulation in the brain (ApoE-SLN) [20][21]. Resveratrol functionalized with apolipoprotein E can be delivered into the brain by loading it into SLNs [22]. Andrographolide (AG) was delivered into the brain by loading it into SLNs and using Compritol 888 ATO as a solid lipid in healthy rats; the ability to cross the BBB was tested in vitro and in vivo [23].

This entry is adapted from the peer-reviewed paper 10.3390/ijms24076199

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