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Homogeneous PLGA-lipid nanoparticle as a promising oral vaccine delivery system for ovalbumin
Institution:1. Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, PR China;2. National Key Laboratory of Biochemical Engineering, PLA Key Laboratory of Biopharmaceutical Production & Formulation Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, PR China
Abstract:In this study, a polymeric lipid nanoparticle (NP) (simplified as Lipid NP) was reported as a promising oral vaccine delivery system. The Lipid NPs composed of a hydrophobic polymeric poly(d,l-lactide-co-glycolide) (PLGA) core and a surface coating of lipid monolayer. Membrane emulsification technique was used to obtain uniform-sized Lipid NPs. Ovalbumin (OVA) was used as a model vaccine. Compared with the pure PLGA NPs, the Lipid NPs achieved higher loading capacity (LC) and entrapment efficiency (EE) for the encapsulated OVA. An in vitro oral release profile showed that the OVA-Lipid NPs were with lower initial burst and could protect the loaded OVA from the harsh gastrointestinal (GI) environment for a long time. In addition, a human microfold cell (M-cell) transcytotic assay demonstrated that due to a lipid layer structure on the particle surface, the Lipid NPs showed higher affinity to the M-cells. Since the M-cell in the intestinal epithelium played an important role in particle transportation as well as intimately associated with the underlying immune cells, the OVA-Lipid NPs effectively induced mucosal and humoral immune responses.
Keywords:Oral delivery  Vaccine  Polymeric lipid nanoparticle  M-cell affinity  NP"}  {"#name":"keyword"  "$":{"id":"kwrd0035"}  "$$":[{"#name":"text"  "_":"nanoparticle  PLGA"}  {"#name":"keyword"  "$":{"id":"kwrd0045"}  "$$":[{"#name":"text"  "$$":[{"#name":"__text__"  "_":"poly("}  {"#name":"small-caps"  "_":"d"}  {"#name":"__text__"  "_":"  "}  {"#name":"small-caps"  "_":"l"}  {"#name":"__text__"  "_":"-lactide-co-glycolide)  OVA"}  {"#name":"keyword"  "$":{"id":"kwrd0055"}  "$$":[{"#name":"text"  "_":"ovalbumin  LC"}  {"#name":"keyword"  "$":{"id":"kwrd0065"}  "$$":[{"#name":"text"  "_":"loading capacity  EE"}  {"#name":"keyword"  "$":{"id":"kwrd0075"}  "$$":[{"#name":"text"  "_":"entrapment efficiency  GI"}  {"#name":"keyword"  "$":{"id":"kwrd0085"}  "$$":[{"#name":"text"  "_":"gastrointestinal  M-cell"}  {"#name":"keyword"  "$":{"id":"kwrd0095"}  "$$":[{"#name":"text"  "_":"microfold cell  PP"}  {"#name":"keyword"  "$":{"id":"kwrd0105"}  "$$":[{"#name":"text"  "_":"Peyer's Patch  FAE"}  {"#name":"keyword"  "$":{"id":"kwrd0115"}  "$$":[{"#name":"text"  "_":"follicle-associated epithelial  HSPC"}  {"#name":"keyword"  "$":{"id":"kwrd0125"}  "$$":[{"#name":"text"  "_":"hydrogenated phosphatidylcholine  PVA"}  {"#name":"keyword"  "$":{"id":"kwrd0135"}  "$$":[{"#name":"text"  "_":"polyvinyl alcohol  Caco-2"}  {"#name":"keyword"  "$":{"id":"kwrd0145"}  "$$":[{"#name":"text"  "_":"colon adenocarcinoma  DMEM"}  {"#name":"keyword"  "$":{"id":"kwrd0155"}  "$$":[{"#name":"text"  "_":"Dulbecco's modified eagle's medium  RPMI"}  {"#name":"keyword"  "$":{"id":"kwrd0165"}  "$$":[{"#name":"text"  "_":"Roswell park memorial institute  DAPI"}  {"#name":"keyword"  "$":{"id":"kwrd0175"}  "$$":[{"#name":"text"  "_":"4  6-diamidino-2-phenylindole  FITC"}  {"#name":"keyword"  "$":{"id":"kwrd0185"}  "$$":[{"#name":"text"  "_":"fluorescein isothiocyanate  UEA-1"}  {"#name":"keyword"  "$":{"id":"kwrd0195"}  "$$":[{"#name":"text"  "_":"ulex europaeus agglutinin-1  DCM"}  {"#name":"keyword"  "$":{"id":"kwrd0205"}  "$$":[{"#name":"text"  "_":"dichloromethane  SEM"}  {"#name":"keyword"  "$":{"id":"kwrd0215"}  "$$":[{"#name":"text"  "_":"scanning electron microscopy  PBS"}  {"#name":"keyword"  "$":{"id":"kwrd0225"}  "$$":[{"#name":"text"  "_":"phosphate buffer  TEER"}  {"#name":"keyword"  "$":{"id":"kwrd0235"}  "$$":[{"#name":"text"  "_":"trans-epithelial electrical resistance  TEM"}  {"#name":"keyword"  "$":{"id":"kwrd0245"}  "$$":[{"#name":"text"  "_":"transmission electron microscope  ELISA"}  {"#name":"keyword"  "$":{"id":"kwrd0255"}  "$$":[{"#name":"text"  "_":"enzyme-linked immunosorbent assay  HRP"}  {"#name":"keyword"  "$":{"id":"kwrd0265"}  "$$":[{"#name":"text"  "_":"horseradish peroxidase  TMB"}  {"#name":"keyword"  "$":{"id":"kwrd0275"}  "$$":[{"#name":"text"  "_":"tetramethylbenzidine  Ptm"}  {"#name":"keyword"  "$":{"id":"kwrd0285"}  "$$":[{"#name":"text"  "_":"trans-membrane pressure  SED"}  {"#name":"keyword"  "$":{"id":"kwrd0295"}  "$$":[{"#name":"text"  "_":"subepithelial dome  CLSM"}  {"#name":"keyword"  "$":{"id":"kwrd0305"}  "$$":[{"#name":"text"  "_":"confocal scanning microscopy
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