title: Methocel-Lipid Hybrid Nanocarrier for Efficient Oral Insulin Delivery.
abstract: Even with the use of double-emulsion technique for preparation, the hydrophobic nature of solid lipid nanoparticles (SLNs) limits their encapsulation efficiency (EE%) for peptides such as insulin. In this study, we hypothesize that inclusion of Methocel into SLN to form Methocel-lipid hybrid nanocarriers (MLNs) will significantly enhance insulin EE% without compromising the various characteristics of SLN favorable for oral drug delivery. Our data show that incorporation of 2% wt/wt of Methocel A15C had doubled insulin EE% (around 40%) versus conventional SLN prepared using standard double emulsion technique. MLN significantly protected the entrapped insulin against chymotrypsin degradation at gastrointestinal pH. Using intestinal epithelial cells Caco2 as a model, it was shown that MLN could be extensively taken up by Caco2 cells while demonstrating low cytotoxicity. The results indicate that MLN have preserved the key advantages of SLN (biocompatibility, low cytotoxicity, good drug protection, and good interaction with cells) while overcoming their key limitation for efficient peptide entrapment. Based on this, MLN may serve as a promising nanocarrier for oral delivery of peptides.
authors.affiliation: Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, Pennsylvania 19140; 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, Philadelphia, Pennsylvania 19140.
authors.forename: Hui-Yi
authors.initials: HY
authors.lastname: Xue
authors.affiliation: Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, Pennsylvania 19140.
authors.forename: Ngoc T
authors.initials: NT
authors.lastname: Tran
authors.affiliation: Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, Pennsylvania 19140. Electronic address: ho-lun.wong@temple.edu.
authors.forename: Ho Lun
authors.initials: HL
authors.lastname: Wong
mesh_terms: D000284:Administration, Oral; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000008:administration & dosage / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000378:metabolism; D008055:Lipids; D008747:Methylcellulose / Q000008:administration & dosage* / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D007328:Insulin; D008055:Lipids; D008747:Methylcellulose
keywords: encapsulation; nanotechnology; oral drug delivery; peptides; stability; toxicity