title: Development and evaluation of viscosity-enhanced nanocarrier (VEN) for oral insulin delivery.
abstract: Solid lipid nanoparticles (SLN) have demonstrated good potential for oral peptide delivery. However, their hydrophobic nature generally accounts for low peptide entrapment efficiency (EE%). In this study, a new strategy was adopted to improve peptide EE% by incorporating a hydrophilic viscosity-enhancing agent (VA) within SLN cores to develop viscosity enhanced nanocarriers (VEN). Three agents namely, propylene glycol (PG), polyethylene glycol (PEG) 400 and PEG 600, were tested with human insulin serving as a model peptide drug. The effects of VA were both concentration- and type-dependent. 70% w/w PG had achieved the highest EE% (54.5%), versus the two PEGs, compared to only 20.4% in unmodified SLN. PG based VEN had demonstrated good dispersion stability at gastrointestinal (GI) pHs and preferential uptake by intestinal Caco2 cells while showing low cytotoxicity. Additionally, they preserved the integrity of insulin and significantly protected it against GI enzymatic degradation. Freeze dried VEN had shown good stability upon storage at -20°C. Orally administered insulin-VEN had achieved good hypoglycemic effect in fasted rats with relative bioavailability of 5.1%. To conclude, an easily implementable technique to improve peptide entrapment within SLN has been validated, and the resulting VEN had proved promising efficacy for oral peptide delivery.
authors.affiliation: Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, PA 19140, USA; Pharmaceutics Department, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
authors.forename: Mariam
authors.initials: M
authors.lastname: Boushra
authors.affiliation: Pharmaceutics Department, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
authors.forename: Sozan
authors.initials: S
authors.lastname: Tous
authors.affiliation: Pharmaceutics Department, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
authors.forename: Gihan
authors.initials: G
authors.lastname: Fetih
authors.affiliation: Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Korzekwa
authors.affiliation: Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, PA 19140, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Lebo
authors.affiliation: Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Hui Yi
authors.initials: HY
authors.lastname: Xue
authors.affiliation: Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, PA 19140, USA. Electronic address: ho-lun.wong@temple.edu.
authors.forename: Ho Lun
authors.initials: HL
authors.lastname: Wong
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014783:Viscosity
chemical_list: D004337:Drug Carriers; D007328:Insulin
keywords: Encapsulation efficiency; Insulin; Oral delivery; Peptide; Propylene glycol; Solid lipid nanoparticles