Chitosan-Hyaluronan Nanoparticles for Vinblastine Sulfate Delivery: Characterization and Internalization Studies on K-562 Cells

Chitosan is a positively charged polysaccharide obtained through chitin deacetylation. It belongs to a group of biodegradable, bioavailable, and non-toxic materials of natural origin; thus, it is a promising matrix for creating delivery systems of different active agents. Recently, much attention has been paid to nanodelivery systems as carriers to enable better bioavailability, and thus higher efficiency of the loaded drug. The present review is focused on the progress in chitosan-based nanoparticles for the targeted delivery of antitumor drugs. The paper discusses literature reports from the last three years in which chitosan nanoparticles were applied as carriers for active substances used in antitumor therapy and potential new drugs with anticancer properties. Special attention was paid to the different treatments applied to increase the therapeutic effectiveness and minimize the side effects of a specific active substance.

Section: Cs Np Platforms For a Specific Drug Deliverymentioning

confidence: 99%

Chitosan-Based Nanoparticles with Optimized Parameters for Targeted Delivery of a Specific Anticancer Drug—A Comprehensive Review

Kurczewska

2023

“…For instance, CS has been reported to form a nano-complex with hyaluronan which efficiently encapsulated vinblastine sulfate, a potential cytotoxic drug against myeloid leukemia. This optimized cargo demonstrated active targeting and sustained therapeutic effects in vitro [ 70 ]. More importantly, CS NP has been shown to form stable complexes with miR-217 [ 71 ], and miR-122 [ 72 ] in the treatment of HCC, as well as with miR-200c [ 73 , 74 ], and miR-34a [ 75 , 76 ] in the treatment of breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Preparation and Optimization of MiR-375 Nano-Vector Using Two Novel Chitosan-Coated Nano-Structured Lipid Carriers as Gene Therapy for Hepatocellular Carcinoma

Soliman,

Wen,

Kandil

et al. 2024

Currently, there is still a lack of effective carriers with minimal side effects to deliver therapeutic miRNA. Thus, it is crucial to optimize novel drug delivery systems. MiR-375 has proven superior therapeutic potency in Hepatocellular carcinoma (HCC). The purpose of this study was to fabricate 2 novel and smart nano-carriers for the transportation efficiency of miR-375 in HCC cells and enhance its anti-tumor effects. We established the miR-375 construct through the pEGP- miR expression vector. Two nano-carriers of solid/liquid lipids and chitosan (CS) were strategically selected, prepared by high-speed homogenization, and optimized by varying nano-formulation factors. Thus, the two best nano-formulations were designated as F1 (0.5% CS) and F2 (1.5% CS) and were evaluated for miR-375 conjugation efficiency by gel electrophoresis and nanodrop assessment. Then, physio-chemical characteristics and stability tests for the miR-375 nano-plexes were all studied. Next, its efficiencies as replacement therapy in HepG2 cells have been assessed by fluorescence microscopy, flow cytometry, and cytotoxicity assay. The obtained data showed that two cationic nanostructured solid/liquid lipid carriers (NSLCs); F1 and F2 typically had the best physio-chemical parameters and long-term stability. Moreover, both F1 and F2 could form nano-plexes with the anionic miR-375 construct at weight ratios 250/1 and 50/1 via electrostatic interactions. In addition, these nano-plexes exhibited physical stability after three months and protected miR-375 from degradation in the presence of 50% fetal bovine serum (FBS). Furthermore, both nano-plexes could simultaneously deliver miR-375 into HepG2 cells and they ensure miR re-expression even in the presence of 50% FBS compared to free miR-375 (p-value < 0.001). Moreover, both F1 and F2 alone significantly exhibited minimal cytotoxicity in treated cells. In contrast, the nano-plexes significantly inhibited cell growth compared to free miR-375 or doxorubicin (DOX), respectively. More importantly, F2/miR-375 nano-plex exhibited more anti-proliferative activity in treated cells although its IC50 value was 55 times lower than DOX (p-value < 0.001). Collectively, our findings clearly emphasized the multifunctionality of the two CS-coated NSLCs in terms of their enhanced biocompatibility, biostability, conjugation, and transfection efficiency of therapeutic miR-375. Therefore, the NSLCs/miR-375 nano-plexes could serve as a novel and promising therapeutic strategy for HCC.

“…To build the LbL assembly, we chose three specific polyelectrolytes: a layer of siRNA, to increase the loading cargo, poly-l-arginine, a polycation that could boost the endosomal escape of LbL LNPs, and hyaluronic acid, a natural target of CD44 receptors [ 29 ] that can direct the LNPs to CD44-overexpressing cancer cells [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

Modulating the Nature of Ionizable Lipids and Number of Layers in Hyaluronan-Decorated Lipid Nanoparticles for In Vitro Delivery of RNAi

Passos Gibson,

Tahiri,

Gilbert

et al. 2024

Lipid nanoparticles (LNPs) have established their position as nonviral vectors for gene therapy. Tremendous efforts have been made to modulate the properties of LNPs to unleash their full clinical potential. Among the strategies being pursued, the layer-by-layer (LbL) technique has gained considerable attention in the biomedical field. Illuminated by our previous work, here we investigate if the LbL approach could be used to modify the LNP cores formulated with three different ionizable lipids: DODMA, MC3, and DODAP. Additionally, we wondered if more than three layers could be loaded onto LNPs without disrupting their gene transfection ability. Taking advantage of physicochemical analysis, as well as uptake and gene silencing studies, we demonstrate the feasibility of modifying the surface of LNPs with the LbL assembly. Precisely, we successfully modified three different LNPs using the layer-by-layer strategy which abrogated luciferase activity in vitro. Additionally, we constructed a 5×-layered HA-LNP containing the MC3 ionizable lipid which outperformed the 3×-layered counterpart in transfecting miRNA-181-5p to the pediatric GBM cell line, as a proof-of-concept in vitro experiment. The method used herein has been proven reproducible, of easy modification to adapt to different ionizable lipid-containing LNPs, and holds great potential for the translation of RNA-based therapeutic strategies.