title: Intraoral film containing insulin-phospholipid microemulsion: formulation and in vivo hypoglycemic activity study.
abstract: Non-invasive administration of insulin is expected for better diabetes mellitus therapy. In this report, we developed intraoral preparation for insulin. Insulin was encapsulated into nanocarrier using self-assembly emulsification process. To increase lipophilicity of insulin, it was dispersed in phospholipid resulted in insulin-phospholipid solid dispersion. The microemulsion formula was established from our previous work which contained glyceryl monooleate (GMO), Tween 20, and polyethylene glycol (PEG 400) in a ratio of 1:8:1. To confirm the formation of insulin-phospholipid solid dispersion, PXRD, FTIR spectroscopy, and Raman spectroscopy were performed. Then, the microemulsion was evaluated for droplet size and distribution, zeta potential, entrapment efficiency, physical stability, and Raman spectroscopy. In addition, microemulsion with expected characteristic was evaluated for in vitro release, in vitro permeation, and in vivo activity. The droplets size of ∼100 nm with narrow distribution and positive charge of +0.56 mV were formed. The insulin encapsulated in the oil droplet was accounted of >90%. Water-soluble chitosan seems to be a promising film matrix polymer which also functioned as insulin release controller. Oral administration of insulin microemulsion to healthy Swiss-Webster mice showed hypoglycemic effect indicating the success of this protein against a harsh environment of the gastrointestinal tract. This effectiveness significantly increased by fourfold as compared to free insulin. Taken together, microemulsion seems to be a promising carrier for oral delivery of insulin.
authors.affiliation: School of Pharmacy, Bandung Institute of Technology, Ganesha 10, Bandung, 40132, Indonesia, hrachma@yahoo.com.
authors.forename: Heni
authors.initials: H
authors.lastname: Rachmawati
authors.forename: Bernard Manuel
authors.initials: BM
authors.lastname: Haryadi
authors.forename: Kusnandar
authors.initials: K
authors.lastname: Anggadiredja
authors.forename: Veinardi
authors.initials: V
authors.lastname: Suendo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D004655:Emulsions / Q000008:administration & dosage* / Q000737:chemistry; D005260:Female; D005989:Glycerides / Q000008:administration & dosage / Q000737:chemistry; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D010316:Particle Size; D010743:Phospholipids / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D005989:Glycerides; D007004:Hypoglycemic Agents; D007328:Insulin; D010743:Phospholipids; D011108:Polymers; D011092:Polyethylene Glycols; D048271:Chitosan; C005953:monoolein