title: Self-assembly of green tea catechin derivatives in nanoparticles for oral lycopene delivery.
abstract: Lycopene is a natural anti-oxidant that has attracted much attention due to its varied applications such as protection against loss of bone mass, chronic diseases, skin cancer, prostate cancer, and cardiovascular disease. However, high instability and extremely low oral bioavailability limit its further clinical development. We selected a green tea catechin derivative, oligomerized (-)-epigallocatechin-3-O-gallate (OEGCG) as a carrier for oral lycopene delivery. Lycopene-loaded OEGCG nanoparticles (NPs) were prepared by a nano-precipitation method, followed by coating with chitosan to form a shell. This method not only can easily control the size of the NP to be around 200nm to improve its bioavailability, but also can effectively protect the lycopene against degradation due to EGCG's anti-oxidant property. OEGCG was carefully characterized with nuclear magnetic resonance spectroscopy and mass spectrometry. Lycopene-loaded polylactic-co-glycolic acid (PLGA) NPs were prepared by the same method. Chitosan-coated OEGCG/lycopene NPs had a diameter of 152±32nm and a ζ-potential of 58.3±4.2mv as characterized with transmission electron microscopy and dynamic light scattering. The loading capacity of lycopene was 9% and encapsulation efficiency was 89%. FT-IR spectral analysis revealed electrostatic interaction between OEGCG and chitosan. Freeze drying of the NPs was also evaluated as a means to improve shelf life. Dynamic light scattering data showed that no aggregation occurred, and the size of the NP increased 1.2 times (Sf/Siratio) in the presence of 10% sucrose after freeze drying. The in vitro release study showed slow release of lycopene in simulated gastric fluid at acidic pH and faster release in simulated intestinal fluid. In an in vivo study in mice, lycopene pharmacokinetic parameters were improved by lycopene/OEGCG/chitosan NPs, but not improved by lycopene/PLGA/chitosan NPs. The self-assembled nanostructure of OEGCG combined with lycopene may be a promising application in oral drug delivery in various indications.
authors.affiliation: The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA.
authors.forename: Weikun
authors.initials: W
authors.lastname: Li
authors.affiliation: The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA; Department of Physiology, Veterinary Medicine Faculty, Uludag University, Bursa, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Yalcin
authors.affiliation: Center for Functional Genomics, University at Albany, Rensselaer, NY, USA.
authors.forename: Qishan
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Center of Excellence for Osteoporosis Research, Department of Clinical Biochemistry, Faculty of Medicine and King Abdulaziz University Hospital, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Mohammed-Salleh M
authors.initials: MM
authors.lastname: Ardawi
authors.affiliation: The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA. Electronic address: shaker.mousa@acphs.edu.
authors.forename: Shaker A
authors.initials: SA
authors.lastname: Mousa
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D002338:Carotenoids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D000077276:Lycopene; D008297:Male; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D013662:Tea / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D004337:Drug Carriers; D013662:Tea; D002338:Carotenoids; D002392:Catechin; C045651:epigallocatechin gallate; D000077276:Lycopene
keywords: Bioavailability; Chitosan; LC-MS/MS; Lycopene; Oral delivery; Polymeric nanoparticles