title: Self-assembled polymeric nanoparticle of PEGylated chitosan-ceramide conjugate for systemic delivery of paclitaxel.
abstract: Chitosan has been widely explored as one of the most favorable biomaterials for various pharmaceutical applications due to its biodegradability and biocompatibility. Here, we report novel PEGylated-chitosan-ceramide (PEG-CS-CE) that forms stable polymeric nanoparticles capable of functioning as efficient carriers of hydrophobic drug molecules. The chitosan-ceramide conjugate (CS-CE) was linked with amine-polyethyleneglycol (NH2-PEG2000) by using dicyclohexylcarbodiimide/N-hydroxysuccinimide (DCC-NHS) to obtain PEG-CS-CE that could exhibit steric stabilization in biological environments. The structure of the conjugate was determined by proton ((1)H) NMR and FT-IR spectrometry. Under suitable conditions, the PEG-CS-CE self-assembled to form colloidally stable nanoparticles with a mean diameter of ∼ 200 nm. Further, hydrophobic anti-tumor agent paclitaxel (PTX) was incorporated into the polymeric nanoparticle with 90% loading efficiency and 11.3% loading capacity via an emulsion-solvent evaporation method. The PTX-loaded PEG-CS-CE nanoparticle showed sustained release and exhibited higher cellular uptake and a comparable cytotoxic efficacy to that of free PTX on B16F10 melanoma and MCF-7 human breast adenocarcinoma cell lines. The empty nanoparticle showed no toxicity, indicating that the co-polymer is safe to use in drug delivery. The polymeric nanoparticle PEG-CS-CE developed by us represent promising nanocarriers of hydrophobic drug molecules.
authors: College of Pharmacy, Gachon University , Incheon , South Korea.
authors: Gantumur
authors: G
authors: Battogtokh
authors: Young Tag
authors: YT
authors: Ko
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D002518:Ceramides / Q000737:chemistry*; D048271:Chitosan / Q000737:chemistry*; D004024:Dicyclohexylcarbodiimide / Q000737:chemistry; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006801:Humans; D061986:MCF-7 Cells; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013388:Succinimides / Q000737:chemistry; D013678:Technology, Pharmaceutical
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002518:Ceramides; D004337:Drug Carriers; D008823:Micelles; D013388:Succinimides; D011092:Polyethylene Glycols; D004024:Dicyclohexylcarbodiimide; D048271:Chitosan; C001426:N-hydroxysuccinimide; D017239:Paclitaxel
keywords: Ceramide; PEGylation; chitosan; paclitaxel; polymeric nanoparticle