title: Multilayer-Coated Liquid Crystalline Nanoparticles for Effective Sorafenib Delivery to Hepatocellular Carcinoma.
abstract: Hepatocellular carcinoma is one of the most common cancers in adults and develops due to activation of oncogenes and inactivation of tumor suppressor genes. Sorafenib (SF) is a U.S. Food and Drug Administration (FDA) approved drug for the treatment of hepatocellular carcinoma. However, its clinical use is limited by its poor aqueous solubility and undesirable side effects. Monoolein-based liquid crystalline nanoparticles (LCN) are self-assembled structures that have been determined as promising drug-delivery vehicles. Therefore, the main aim of this study was to prepare layer-by-layer (LbL) polymer-assembled SF-loaded LCNs (LbL-LCN/SF) for effective delivery of SF to hepatocellular carcinoma. Results revealed that LbL-LCN/SF presented optimum particle size (∼165 nm) and polydispersity index (PDI, ∼0.14) with appropriate polymer layer assembly confirmed by transmission electron microscopy (TEM) and atomic force microscopy (AFM). Furthermore, LbL-LCN/SF effectively controlled burst release and exhibited pH-sensitive release of SF, thereby increasing drug release in the acidic microenvironment of tumor cells. Compared to free SF and bare LCN, the hemolytic activity of LbL-LCN/SF was significantly reduced (p<0.01). Interestingly, LbL-LCN/SF was more cytotoxic to HepG2 cells than the free drug was. Additionally, high cellular uptake and greater apoptotic effects of LbL-LCN/SF in HepG2 cells indicates superior antitumor effects. Therefore, LbL-LCN/SF is a potentially effective formulation for hepatocellular carcinoma.
authors: College of Pharmacy, Yeungnam University , 280 Daehak-Ro, Gyeongsan, Gyeongsanbuk-do 712-749, South Korea.
authors: Raj Kumar
authors: RK
authors: Thapa
authors: College of Pharmacy, Yeungnam University , 280 Daehak-Ro, Gyeongsan, Gyeongsanbuk-do 712-749, South Korea.
authors: Ju Yeon
authors: JY
authors: Choi
authors: College of Pharmacy, Yeungnam University , 280 Daehak-Ro, Gyeongsan, Gyeongsanbuk-do 712-749, South Korea.
authors: Bijay K
authors: BK
authors: Poudel
authors: College of Pharmacy, Yeungnam University , 280 Daehak-Ro, Gyeongsan, Gyeongsanbuk-do 712-749, South Korea.
authors: Tran Tuan
authors: TT
authors: Hiep
authors: College of Pharmacy, Yeungnam University , 280 Daehak-Ro, Gyeongsan, Gyeongsanbuk-do 712-749, South Korea.
authors: Shiva
authors: S
authors: Pathak
authors: College of Pharmacy, Yeungnam University , 280 Daehak-Ro, Gyeongsan, Gyeongsanbuk-do 712-749, South Korea.
authors: Biki
authors: B
authors: Gupta
authors: College of Pharmacy, Hanyang University , 55, Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, South Korea.
authors: Han-Gon
authors: HG
authors: Choi
authors: College of Pharmacy, Yeungnam University , 280 Daehak-Ro, Gyeongsan, Gyeongsanbuk-do 712-749, South Korea.
authors: Chul Soon
authors: CS
authors: Yong
authors: College of Pharmacy, Yeungnam University , 280 Daehak-Ro, Gyeongsan, Gyeongsanbuk-do 712-749, South Korea.
authors: Jong Oh
authors: JO
authors: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002152:Calorimetry, Differential Scanning; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D065546:Drug Liberation; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D006461:Hemolysis; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D050866:Liquid Crystals / Q000737:chemistry*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D010671:Phenylurea Compounds / Q000737:chemistry* / Q000633:toxicity; D011108:Polymers / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077157:Sorafenib; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D004337:Drug Carriers; D010671:Phenylurea Compounds; D011108:Polymers; D009536:Niacinamide; D000077157:Sorafenib
keywords: hepatocellular carcinoma; layer-by-layer; liquid crystalline nanoparticles; multilayer; sorafenib