title: Insulin-loaded alginic acid nanoparticles for sublingual delivery.
abstract: Alginic acid nanoparticles (NPs) containing insulin, with nicotinamide as permeation enhancer were developed for sublingual delivery. The lower concentration of proteolytic enzymes, lower thickness and enhanced retention due to bioadhesive property, were relied on for enhanced insulin absorption. Insulin-loaded NPs were prepared by mild and aqueous based nanoprecipitation process. NPs were negatively charged and had a mean size of ∼200 nm with low dispersity index. Insulin loading capacities of >95% suggested a high association of insulin with alginic acid. Fourier Transform Infra-Red Spectroscopy (FTIR) spectra and DSC (Differential Scanning Calorimetry) thermogram of insulin-loaded NPs revealed the association of insulin with alginic acid. Circular dichroism (CD) spectra confirmed conformational stability, while HPLC analysis confirmed chemical stability of insulin in the NPs. Sublingually delivered NPs with nicotinamide exhibited high pharmacological availability (>100%) and bioavailability (>80%) at a dose of 5 IU/kg. The high absolute pharmacological availability of 20.2% and bioavailability of 24.1% in comparison with subcutaneous injection at 1 IU/kg, in the streptozotocin-induced diabetic rat model, suggest the insulin-loaded alginic acid NPs as a promising sublingual delivery system of insulin.
authors.affiliation: a Department of Pharmaceutical Science and Technology , Institute of Chemical Technology , Mumbai , Maharashtra , India.
authors.forename: Nilam H
authors.initials: NH
authors.lastname: Patil
authors.affiliation: a Department of Pharmaceutical Science and Technology , Institute of Chemical Technology , Mumbai , Maharashtra , India.
authors.forename: Padma V
authors.initials: PV
authors.lastname: Devarajan
mesh_terms: D000268:Adhesiveness; D000286:Administration, Sublingual; D000464:Alginates / Q000737:chemistry*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D009061:Mouth Mucosa / Q000378:metabolism; D053758:Nanoparticles; D036103:Nanotechnology; D009536:Niacinamide / Q000737:chemistry; D065568:Oral Mucosal Absorption; D010316:Particle Size; D010539:Permeability; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000464:Alginates; D015415:Biomarkers; D001786:Blood Glucose; D004337:Drug Carriers; D006603:Hexuronic Acids; D007004:Hypoglycemic Agents; D007328:Insulin; D009536:Niacinamide; D020723:Glucuronic Acid
keywords: Circular dichroism; FTIR; diabetic rats; insulin; nanoparticles; permeation enhancer; stability; sublingual delivery