title: Enhancement of the intranasal delivery of insulin via a novel mucoadhesive Carbopol gel.
abstract: OBJECTIVE
  The objectives of this study were to develop an intranasal insulin gel using Carbopol homogenization rather than neutralization and to examine the effectiveness of the gel compared with a subcutaneous injection.
  
  
  METHODS
  Four factors, namely the molecular weight of polyethylene glycol (PEG), the concentration of Carbopol, the temperature of preparation and the type of absorption enhancer, were evaluated for their effect on viscosity and in-vitro insulin release. Bioavailability of insulin from selected formulations was compared with an intranasal solution and subcutaneous injection in rabbits.
  
  
  RESULTS
  Increasing the molecular weight of PEG and Carbopol concentration increased the gel viscosity and changed the release mechanism from diffusion to case II transport. Applying heat during preparation resulted in a lower viscosity gel and increased the in-vitro insulin release. Among the two enhancers studied, sodium deoxycholate resulted in a higher viscosity gel than Tween 80. In vivo, the intranasal gel showed a stronger and longer hypoglycaemic effect with 1.7- and 3.1-fold higher maximum decrease in blood glucose level and area above the curve, respectively, compared with the subcutaneous injection.
  
  
  CONCLUSIONS
  The homogenized Carbopol intranasal gel could be an efficient noninvasive way for insulin delivery but selection of gel components and method of preparation are critical for achieving the most desired effect.
authors.affiliation: Holding Company for Biological Products and Vaccines, 51 Wizaret El-Zeraa, Agouza, Giza, Egypt.
authors.forename: Walaa Ahmed
authors.initials: WA
authors.lastname: El-Dakrouri
authors.forename: Howida Kamal
authors.initials: HK
authors.lastname: Ibrahim
authors.forename: Mohamed Khaled
authors.initials: MK
authors.lastname: Ghorab
authors.forename: Mahmoud Mohamed
authors.initials: MM
authors.lastname: Ghorab
mesh_terms: D000180:Acrylic Resins; D000269:Adhesives; D000281:Administration, Intranasal; D000287:Administration, Topical; D000818:Animals; D019540:Area Under Curve; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D003840:Deoxycholic Acid / Q000737:chemistry*; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry*; D005782:Gels; D006358:Hot Temperature; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000737:chemistry*; D011136:Polysorbates / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry*; D011817:Rabbits; D014783:Viscosity
chemical_list: D000180:Acrylic Resins; D000269:Adhesives; D001786:Blood Glucose; D004337:Drug Carriers; D005782:Gels; D007004:Hypoglycemic Agents; D007328:Insulin; D011136:Polysorbates; D011145:Polyvinyls; D003840:Deoxycholic Acid; C006912:carboxypolymethylene; D011092:Polyethylene Glycols