title: Development and in vitro evaluation of core-shell type lipid-polymer hybrid nanoparticles for the delivery of erlotinib in non-small cell lung cancer.
abstract: Core-shell type lipid-polymer hybrid nanoparticles (CSLPHNPs) have emerged as a multifunctional drug delivery platform. The delivery system combines mechanical advantages of polymeric core and biomimetic advantages of the phospholipid shell into a single platform. We report the development of CSLPHNPs composed of the lipid monolayer shell and the biodegradable polymeric core for the delivery of erlotinib, an anticancer drug, clinically used to treat non-small cell lung cancer (NSCLC). Erlotinib loaded CSLPHNPs were prepared by previously reported single-step sonication method using polycaprolactone (PCL) as the biodegradable polymeric core and phospholipid-shell composed of hydrogenated soy phosphatidylcholine (HSPC) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000 (DSPE-PEG2000). Erlotinib loaded CSLPHNPs were characterized for physicochemical properties including mean particle size, polydispersity index (PDI), zeta potential, morphology, thermal and infrared spectral analysis, drug loading, in vitro drug release, in vitro serum stability, and storage stability. The effect of critical formulation and process variables on two critical quality attributes (mean particle size and drug entrapment efficiency) of erlotinib loaded CSLPHNPs was studied and optimized. In addition, in vitro cellular uptake, luminescent cell viability assay and colony formation assay were performed to evaluate efficacy of erlotinib loaded CSLPHNPs in A549 cells, a human lung adenocarcinoma cell line. Optimized erlotinib loaded CSLPHNPs were prepared with mean particle size of about 170nm, PDI<0.2, drug entrapment efficiency of about 66% with good serum and storage stability. The evaluation of in vitro cellular efficacy results indicated enhanced uptake and efficacy of erlotinib loaded CSLPHNPs compared to erlotinib solution in A549 cells. Therefore, CSLPHNPs could be a potential delivery system for erlotinib in the therapy of NSCLC.
authors.affiliation: Plough Center for Sterile Drug Delivery Systems, University of Tennessee Health Science Center, 3 N Dunlap Street, Memphis, TN 38163, USA; Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 881 Madison Avenue, Memphis, TN 38163, USA. Electronic address: bmandal@uthsc.edu.
authors.forename: Bivash
authors.initials: B
authors.lastname: Mandal
authors.affiliation: Plough Center for Sterile Drug Delivery Systems, University of Tennessee Health Science Center, 3 N Dunlap Street, Memphis, TN 38163, USA; Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 881 Madison Avenue, Memphis, TN 38163, USA.
authors.forename: Nivesh K
authors.initials: NK
authors.lastname: Mittal
authors.affiliation: Plough Center for Sterile Drug Delivery Systems, University of Tennessee Health Science Center, 3 N Dunlap Street, Memphis, TN 38163, USA; Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 881 Madison Avenue, Memphis, TN 38163, USA.
authors.forename: Pavan
authors.initials: P
authors.lastname: Balabathula
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 881 Madison Avenue, Memphis, TN 38163, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Thoma
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 881 Madison Avenue, Memphis, TN 38163, USA.
authors.forename: George C
authors.initials: GC
authors.lastname: Wood
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D001692:Biological Transport; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D065546:Drug Liberation; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000737:chemistry*; D014410:Tumor Stem Cell Assay
chemical_list: C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D000970:Antineoplastic Agents; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D011091:Polyesters; D047428:Protein Kinase Inhibitors; C016240:polycaprolactone; D011092:Polyethylene Glycols; D000069347:Erlotinib Hydrochloride
keywords: Core–shell; Drug delivery; Erlotinib; Lipid–polymer hybrid nanoparticles; Non-small cell lung cancer