title: Self-nanoemulsifying drug delivery systems for oral insulin delivery: in vitro and in vivo evaluations of enteric coating and drug loading.
abstract: This study aims at evaluating the combination of self-nanoemulsifying drug delivery systems (SNEDDS) and enteric-coated capsules as a potential delivery strategy for oral delivery of insulin. The SNEDDS preconcentrates, loaded with insulin-phospholipid complex at different levels (0, 2.5 and 10% w/w), were readily dispersed in water to form nanoemulsions of 35 nm and vesicles of 300 nm. The association efficiency of non-complexed insulin in the dispersed SNEDDS was 18.6%, and was increased to 73.1% for insulin-phospholipid complex (at 10% loading level). The morphology of the dispersed SNEDDS changed from nanoemulsion droplets to vesicular structures with increasing complex loading levels. A pH-dependent insulin release profile was observed for SNEDDS filled into capsules coated with the enteric polymer, Eudragit(®) L100. Using a Caco-2 cell model, it was observed that the transport of insulin was enhanced by factors of 7.7- and 9.3- for SNEDDS loaded with 2.5 and 10% complex, respectively. In healthy fasted rats, administration of SNEDDS (10% complex) filled in enteric-coated capsules produced a 2.7-fold and 3.4-fold enhancement in the relative bioavailability and glucose reduction, respectively. This study shows the effectiveness of combining SNEDDS (loaded with insulin-phospholipid complex) with enteric-coated capsules for enhancing the oral absorption and efficacy of insulin.
authors.affiliation: Department of Pharmacy, University of Copenhagen, Denmark.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-48505, Japan.
authors.forename: Angel
authors.initials: A
authors.lastname: Tan
authors.affiliation: Ian Wark Research Institute, University of South Australia, Mawson Lakes Campus, SA 5095, Australia.
authors.forename: Clive A
authors.initials: CA
authors.lastname: Prestidge
authors.affiliation: Department of Pharmacy, University of Copenhagen, Denmark.
authors.forename: Hanne Mørck
authors.initials: HM
authors.lastname: Nielsen
authors.affiliation: Department of Pharmacy, University of Copenhagen, Denmark; Bioneer: FARMA, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: anette.mullertz@sund.ku.dk.
authors.forename: Anette
authors.initials: A
authors.lastname: Müllertz
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001692:Biological Transport; D001786:Blood Glucose / Q000032:analysis; D018938:Caco-2 Cells; D002214:Capsules; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004655:Emulsions; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D053758:Nanoparticles / Q000737:chemistry; D065568:Oral Mucosal Absorption; D011109:Polymethacrylic Acids / Q000737:chemistry; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D002214:Capsules; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004655:Emulsions; D007004:Hypoglycemic Agents; D007328:Insulin; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer
keywords: (R, S) metoprolol (PubChem CID: 157716, 157717); 1-Palmitoyl-2-oleoylphosphatidylcholine (PubChem CID: 5497103); Capric acid triglyceride (PubChem CID: 69310); Caprylic acid triglyceride (PubChem CID: 10850); Enteric coating; Ethanol (PubChem CID: 702); Glyceryl monocaprate (PubChem CID: 92926); Human insulin (PubChem CID: 16129672); Hypoglycemia; Insulin; Mannitol (PubChem CID: 6251); Oral drug delivery; Pharmacokinetic; SNEDDS