title: Surface modification of nanostructure lipid carrier (NLC) by oleoyl-quaternized-chitosan as a mucoadhesive nanocarrier.
abstract: A nanostructure lipid carrier (NLC) composed of solid, and liquid lipid as a core has been developed as a delivery system for hydrophobic drug molecules. The aim of this research was to fabricate an oleoyl-quaternized-chitosan (CS)-coated NLC, where the mucoadhesive property of nanoparticles is enhanced for more efficient drug delivery. NLC loaded with alpha-mangostin (AP), a model hydrophobic drug, were fabricated using a high pressure homogenization process and subsequently coated with CS. The fabricated nanoparticles showed particle sizes in the range of 200-400nm, with low polydispersity, high physical stability and excellent encapsulation efficiency (EE>90%). Additionally, in vitro viability, cytotoxicity and ability of NLC and CS-NLC to affect apoptosis in carcinoma Caco-2 cells were determined using the Triplex assay. Gene expressiom analysis were performed using quantitative reverse transcription Polymerase Chain Reaction (RT-qPCR). Moreover, in vivo toxicological testing of NLCs was conducted in zebrafish embryos. Results indicated that CS-NLC provieded high cytotoxicity than NLC itself. In the case of AP loaded nanoparticles, NLC loaded with AP (AP-NLC), and CS-NLC loaded with AP (CS-AP-NLC) exhibited higher cytotoxicity to Caco-2 over Hela cells. These results indicate that CS-NLC shows enhanced cellular uptake but increased cytotoxicity characteristics over NLC and therefore careful optimization of dosage and loading levels in CS-NLC is needed to allow cancer cell targeting, and for exploiting the potential of these systems in cancer therapy.
authors: Nano Delivery System Laboratory, National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani, 12120, Thailand.
authors: Jakarwan
authors: J
authors: Yostawonkul
authors: Nano Delivery System Laboratory, National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani, 12120, Thailand.
authors: Suvimol
authors: S
authors: Surassmo
authors: Nano-Molecular Target Discovery Laboratory, National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani, 12120, Thailand.
authors: Tawin
authors: T
authors: Iempridee
authors: Nano Safety and Risk Assessment Laboratory, National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani, 12120, Thailand.
authors: Wittaya
authors: W
authors: Pimtong
authors: Nano Delivery System Laboratory, National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani, 12120, Thailand.
authors: Kunat
authors: K
authors: Suktham
authors: Nanoengineered Soft Materials for Environment Laboratory, National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani, 12120, Thailand.
authors: Warayuth
authors: W
authors: Sajomsang
authors: Nanoengineered Soft Materials for Environment Laboratory, National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani, 12120, Thailand.
authors: Pattarapond
authors: P
authors: Gonil
authors: National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani, 12120, Thailand. Electronic address: uracha@nanotec.or.th.
authors: Uracha Rungsardthong
authors: UR
authors: Ruktanonchai
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism; D004337:Drug Carriers; D004339:Drug Compounding; D065546:Drug Liberation; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D013499:Surface Properties; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C000595707:BCL2 protein, human; C494811:BCL2L1 protein, human; C530104:CCND1 protein, human; D004337:Drug Carriers; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D044004:Xanthones; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019938:Cyclin D1; D048271:Chitosan; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; C021053:mangostin
keywords: Alpha-mangostin; Mucoadhesive; Nanostructure lipid carrier; Oleoyl-quaternized-chitosan