title: Paclitaxel-Nanodiamond Nanocomplexes Enhance Aqueous Dispersibility and Drug Retention in Cells.
abstract: Nanodiamonds (NDs) with 5 nm crystalline structures have been recognized as emerging carbon delivery vehicles due to their biocompatible inertness, high surface-to-volume ratio, and energy absorbance properties. In this study, carboxylated nanodiamond (ND-COOH) was reduced to hydroxylated nanodiamond (ND-OH) for stable and pH-independent colloidal dispersity. The poorly water-soluble paclitaxel (PTX) was physically loaded into ND-OH clusters, forming amorphous PTX nanostructure on the interparticle nanocage of the ND substrate. Stable physical PTX loading onto the ND substrate with stable colloidal stability showed enhanced PTX release. ND-OH/PTX complexes retained the sustained release of PTX by up to 97.32% at 70 h, compared with the 47.33% release of bare crystalline PTX. Enhanced PTX release from ND substrate showed low cell viability in Hela, MCF-9, and A549 cancer cells due to sustained release and stable dispersity in a biological aqueous environment. Especially, the IC50 values of ND-OH/PTX complexes and PTX in Hela cells were 0.037 μg/mL and 0.137 μg/mL, respectively. Well-dispersed cellular uptake of suprastructure ND-OH/PTX nanocomplexes was directly observed from the TEM images. ND-OH/PTX nanocomplexes assimilated into cells might provide convective diffusion with high PTX concentration, inducing initial necrosis. This study suggests that poorly water-soluble drugs can be formulated into a suprastructure with ND and acts as a highly concentrated drug reservoir directly within a cell.
authors.affiliation: College of Pharmacy, Dongguk University-Seoul , Gyeonggi 410-820, Republic of Korea.
authors.forename: Dae Gon
authors.initials: DG
authors.lastname: Lim
authors.affiliation: College of Pharmacy, Dongguk University-Seoul , Gyeonggi 410-820, Republic of Korea.
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Jung
authors.affiliation: College of Pharmacy, Dongguk University-Seoul , Gyeonggi 410-820, Republic of Korea.
authors.forename: Hyuk Wan
authors.initials: HW
authors.lastname: Ko
authors.affiliation: School of Chemical Engineering and Material Science, Chung-Ang University , Seoul 156-756, Republic of Korea.
authors.forename: Eunah
authors.initials: E
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Dongguk University-Seoul , Gyeonggi 410-820, Republic of Korea.
authors.forename: Seong Hoon
authors.initials: SH
authors.lastname: Jeong
mesh_terms: D000972:Antineoplastic Agents, Phytogenic; D045744:Cell Line, Tumor; D002470:Cell Survival; D004337:Drug Carriers; D006801:Humans; D058612:Nanodiamonds; D017239:Paclitaxel
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D058612:Nanodiamonds; D017239:Paclitaxel
keywords: carboxylated; cellular uptake; colloidal stability; drug delivery; hydroxylated; nanodiamond; paclitaxel