title: Sequentially releasing dual-drug-loaded PLGA-casein core/shell nanomedicine: design, synthesis, biocompatibility and pharmacokinetics.
abstract: The present study reports an engineered poly-l-lactide-co-glycolic acid (PLGA)-casein polymer-protein hybrid nanocarrier 190±12nm in size entrapping a combination of chemically distinct (hydrophobic/hydrophilic) model drugs. A simple emulsion-precipitation route was adopted to prepare nearly monodispersed nanoparticles with distinct core/shell morphology entrapping paclitaxel (Ptx) in the core and epigallocatechin gallate (EGCG) in the shell, with the intention of providing a sequential and sustained release of these drugs. The idea was that an early release of EGCG would substantially increase the sensitivity of Ptx to cancer, thereby providing improved therapeutics at lower concentrations, with less toxicity. The hemo- and immunocompatibility of the core/shell nanomedicine was established in this study. The core/shell nanoparticles injected via the tail vein in Sprague-Dawley rats did not reveal any organ toxicity as was evident from histopathological evaluations of the major organs. In vivo pharmacokinetic studies in rats by high-performance liquid chromatography confirmed a sustained and sequential release of both the drugs in plasma, indicating prolonged circulation of the nanomedicine and enhanced availability of the drugs when compared to the bare drugs. Overall, the polymer-protein multilayered nanoparticles proved to be a promising platform for nanopolypharmaceutics.
authors.affiliation: Amrita Centre for Nanosciences & Molecular Medicine, Amrita Institute of Medical Sciences & Research Centre, Amrita Vishwa Vidyapeetham, Kochi 682 041, Kerala, India.
authors.forename: Sreeja
authors.initials: S
authors.lastname: Narayanan
authors.affiliation: Amrita Centre for Nanosciences & Molecular Medicine, Amrita Institute of Medical Sciences & Research Centre, Amrita Vishwa Vidyapeetham, Kochi 682 041, Kerala, India.
authors.forename: Maya
authors.initials: M
authors.lastname: Pavithran
authors.affiliation: Amrita Centre for Nanosciences & Molecular Medicine, Amrita Institute of Medical Sciences & Research Centre, Amrita Vishwa Vidyapeetham, Kochi 682 041, Kerala, India.
authors.forename: Aiswarya
authors.initials: A
authors.lastname: Viswanath
authors.affiliation: Amrita Centre for Nanosciences & Molecular Medicine, Amrita Institute of Medical Sciences & Research Centre, Amrita Vishwa Vidyapeetham, Kochi 682 041, Kerala, India.
authors.forename: Dhanya
authors.initials: D
authors.lastname: Narayanan
authors.affiliation: Amrita Centre for Nanosciences & Molecular Medicine, Amrita Institute of Medical Sciences & Research Centre, Amrita Vishwa Vidyapeetham, Kochi 682 041, Kerala, India.
authors.forename: Chandini C
authors.initials: CC
authors.lastname: Mohan
authors.affiliation: Amrita Centre for Nanosciences & Molecular Medicine, Amrita Institute of Medical Sciences & Research Centre, Amrita Vishwa Vidyapeetham, Kochi 682 041, Kerala, India.
authors.forename: K
authors.initials: K
authors.lastname: Manzoor
authors.affiliation: Amrita Centre for Nanosciences & Molecular Medicine, Amrita Institute of Medical Sciences & Research Centre, Amrita Vishwa Vidyapeetham, Kochi 682 041, Kerala, India. Electronic address: deepthymenon@aims.amrita.edu.
authors.forename: Deepthy
authors.initials: D
authors.lastname: Menon
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis*; D002364:Caseins / Q000737:chemistry* / Q000633:toxicity; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000097:blood; D006801:Humans; D007208:Indocyanine Green / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D019344:Lactic Acid / Q000737:chemistry* / Q000633:toxicity; D008422:Materials Testing; D051379:Mice; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity / Q000648:ultrastructure; D009928:Organ Specificity / Q000187:drug effects; D017239:Paclitaxel / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000633:toxicity; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D001672:Biocompatible Materials; D002364:Caseins; D016207:Cytokines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002392:Catechin; C045651:epigallocatechin gallate; D007208:Indocyanine Green; D017239:Paclitaxel
keywords: Casein; Core/shell nanoparticles; Hemocompatibility; PLGA; Sequential release