Hyaluronic Acid Modified Nanostructured Lipid Carrier for Targeting Delivery of Kaempferol to NSCLC: Preparation, Optimization, Characterization, and Performance Evaluation In Vitro

Abstract

Lung cancer seriously threatens the health of human beings, with non-small cell lung cancer (NSCLC) accounting for 80%. Nowadays, the potential position of nano-delivery in treating cancer has been the subject of continuous research. The present research aimed to prepare two molecular weight hyaluronic acid (HA)-modified kaempferol (KA)-loaded nanostructured lipid carriers (HA-KA-NLCs) by the method of melting ultrasonic and electrostatic adsorption, and to assess the antitumor effect of the preparations on A549 cells. The characterization and safety evaluation of the preparations illustrated that they are acceptable for drug delivery for cancer. Subsequently, differential scanning calorimetry (DSC) curve and transmission electron microscopy (TEM) images indicated that the drug was adequately incorporated in the carrier, and the particle appeared as a sphere. Moreover, HA-KA-NLC showed predominant in vitro antitumor effects, inhibiting proliferation, migration, and invasion, promoting apoptosis and increasing cellular uptake of A549 cells. Otherwise, the Western blot assay revealed that preparations could activate epithelial-mesenchymal transition (EMT)-related signaling pathways and modulate the expression of E-cadherin, N-cadherin, and Vimentin in A549 cells. Our present findings demonstrated that HA-KA-NLC could be considered as a secure and effective carrier for targeted tumor delivery and may have potential application prospects in future clinic therapy of NSCLC.

The Anticancer Potential of Kaempferol: A Systematic Review Based on In Vitro Studies

“…Twelve of the studies included in this systematic review explored the role of cellular toxicity of KMP in lung cancer cells using A549 [22,44,[47][48][49]53,70,73,80] or H460 cells [27,60,61]. The findings were consistent, indicating a strong cytotoxicity of KMP.…”

“…Table 1 shows the main findings according to type of tumor. Most of the studies included in the present review explored the effects of KMP on tumor cell death [10,12,22,[27][28][29][30][31][32]35,36,40,46,[51][52][53][55][56][57]62,63,66,70,[74][75][76][77]80,81]. These studies reported the apoptosis-inducing properties of KMP, which can be partially attributed to its impacts on the MAPK pathway.…”

Hyaluronic Acid-Mediated Phenolic Compound Nanodelivery for Cancer Therapy

“…These hydroxyls are also able to chelate metal ions and, thus, hamper the metal-catalyzed generation of reactive oxygen substances (ROS) and their oxidant activity. According to our research of the literature, the flavonoids that have been included in HA-coated delivery nanosystems investigated against cancer in the last 5 years are the two flavonols: kaempferol [34] and quercetin (QU) [35][36][37][38][39][40][41], the flavanol epigallocatechin-3-gallate (EGCG) [42][43][44][45][46][47] the flavanone naringenin [48], the isoflavone formononetin [49], and a mix of anthocyanins extracted from corn [50]. Between brackets are reported the number of compounds belonging to each class or subclass according to this classification.…”

“…Kaempferol, another flavonol, was recently encapsulated in a HA-modified nanostructured lipid carrier for the therapy of lung cancer [ 34 ]. The authors constructed two NPs and tested them against A549 lung carcinoma cells.…”

Grafted Microparticles Based on Glycidyl Methacrylate, Hydroxyethyl Methacrylate and Sodium Hyaluronate: Synthesis, Characterization, Adsorption and Release Studies of Metronidazole

“…Among the natural polymers, chitosan, pectin, alginate, starch and dextran are used to prepare microparticles loaded with different drugs to treat periodontal diseases [ 4 , 5 , 6 ]. Another important polysaccharide, hyaluronic acid, which is used in the cosmetic industry, prepares the scaffold for tissue engineering for drug delivery, disease diagnoses and biomedical imaging; it represents an ideal candidate to obtain polymeric materials for the dental field [ 7 , 8 , 9 , 10 ]. The use of polymeric microparticles in dentistry has been increasing due to the excellent properties of both polymeric materials (good surface, biological and mechanical properties, low manufacturing cost, simple synthesis methods) as well as of microparticles (high surface/volume ratio, good accessibility to the site of action due to their size, stability in biological fluids, drug transport capacity, decreased frequency and intensity of adverse effects) [ 11 , 12 ].…”