title: Films loaded with insulin-coated nanoparticles (ICNP) as potential platforms for peptide buccal delivery.
abstract: The goal of this investigation was to develop films containing insulin-coated nanoparticles and evaluate their performance in vitro as potential peptide delivery systems. To incorporate insulin into the films, a new antisolvent co-precipitation fabrication process was adapted to obtain insulin-coated nanoparticles (ICNPs). The ICNPs were embedded in polymeric films containing a cationic polymethacrylate derivative (ERL) or a combination of ERL with hydroxypropyl methylcellulose (HPMC). ICNP-loaded films were characterized for morphology, mucoadhesion, and insulin release. Furthermore, in vitro insulin permeation was evaluated using a cultured tridimensional human buccal mucosa model. The antisolvent co-precipitation method was successfully adapted to obtain ICNPs with 40% (w/w) insulin load, achieving 323±8nm particles with a high zeta potential of 32.4±0.8mV, indicating good stability. High yields were obtained after manufacture and the insulin content did not decrease after one month storage. ICNP-embedded films using ERL as the polymer matrix presented excellent mucoadhesive and insulin release properties. A high permeation enhancement effect was observed for ICNP-loaded ERL films in comparison with ICNP-loaded ERL-HPMC films and a control insulin solution. ICNP-loaded ERL formulations were found to be more effective in terms of film performance and insulin permeation through the human buccal mucosa model, and thus are a promising delivery system for buccal administration of a peptide such as insulin.
authors.affiliation: Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago 8380494, Chile. Electronic address: jomorales@ciq.uchile.cl.
authors.forename: Javier O
authors.initials: JO
authors.lastname: Morales
authors.affiliation: College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Huang
authors.affiliation: College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Williams
authors.affiliation: College of Pharmacy, University of New Mexico, Albuquerque, NM 87131, USA.
authors.forename: Jason T
authors.initials: JT
authors.lastname: McConville
mesh_terms: D002610:Cheek; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D006801:Humans; D065347:Hypromellose Derivatives / Q000737:chemistry; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D053758:Nanoparticles
chemical_list: D004337:Drug Carriers; D007328:Insulin; D065347:Hypromellose Derivatives
keywords: Buccal delivery; Insulin-coated nanoparticles; Permeation enhancement; Protein and peptide delivery