A promising approach to develop nanostructured lipid carriers from solid lipid nanoparticles: preparation, characterization, cytotoxicity and nucleic acid binding ability

Abstract

We aimed to develop nanostructured lipid carriers (NLCs) displaying similar characteristics-particle size, polydispersity index, and zeta potential-with the model solid lipid nanoparticles (SLNs) for better comparability. By considering the hydrophilic-lipophilic balance (HLB) values of solid and liquid lipids, five out of six NLCs and eight out of eight cationic NLCs (cNLCs) were successfully prepared with similar characteristics to their precursor SLN and cationic SLNs (cSLNs), respectively. Among cationic formulations, two cSLNs containing different surfactant/co-surfactant concentrations (4% and 8% S/CoS; w/w) and their cNLC versions prepared with Labrafac lipophile WL 1349 (LWL) or Labrafac PG were selected to compare cytotoxicity, stability, and nucleic acid binding ability. All formulations are well-tolerated by L-929 cells, cSLNs being least toxic. The formulations containing 4% S/CoS had higher stability after 24months. All nanoparticles formed complexes with pDNA (Binding ability: cNLCs>cSLNs). cSLN and LWL-cNLC containing 4% S/CoS showed the highest pDNA binding capacity in each group, and their spherical/oval shape was revealed by electron microscopy. However, they did not form complexes with siRNA. The developed approach has the potential to simplify the production of (c)NLCs having similar physicochemical properties with the optimum (c)SLN and may provide better insight for (c)SLN vs. (c)NLC comparison studies.

Development of EphA2 siRNA-loaded lipid nanoparticles and combination with a small-molecule histone demethylase inhibitor in prostate cancer cells and tumor spheroids

“…Formulations were prepared by the modified hot microemulsion method as described previously [32]. Briefly, solid lipids (Precirol: Compritol; 1.25%: 1.25%; w/w), the mixture of surfactants and co-surfactant (KRH40: S80: PG; 1.5%: 0.5%: 2%; w/w), and cationic lipid DDAB for DDAB-cSLN or DOTMA for DOTMA-cSLN (0.5% w/w) were weighed into a glass vial and stirred at the temperature above the melting points of solid lipids (80°C).…”

“…Gel retardation (shift) assay was conducted using agarose gel electrophoresis to determine the optimal amount of the formulation for complex formation with siRNA [32]. Briefly, different amounts of cSLN with a constant amount of siRNA (67 ng) were incubated at room temperature on a shaker (500 rpm, 30 min).…”

Innovations in Biomaterial Design toward Successful RNA Interference Therapy for Cancer Treatment

“…Thus far, these systems have only been explored using traditional chemotherapeutics with success. [ 71–73 ] Because of the promise that NLC‐based systems have for the delivery of chemotherapeutics with higher encapsulation and drug loading efficiencies compared to traditional liposomal systems, further investigation into their potential as RNAi carriers for cancer therapy would be ideal.…”

Nanocarrier drug resistant tumor interactions: novel approaches to fight drug resistance in cancer

“…The advantages of SLNs for drug delivery systems include the utilization of biocompatible and biodegradable ingredients, the lack of application of organic solvents, drug protection from environmental damage, high physical stability, ease of preparation, controlled drug release, and ability of CNS targeting [ 86 ] . SLNs have been successfully used to encapsulate lipophilic and hydrophilic medicines [ 87 ] , peptides/proteins [ 88 ] , and nucleic acids [ 89 ] . In recent years, the use of SLNs for anticancer drug delivery has become a rapidly growing field of study [ 90 , 91 ] .…”