title: Eudragit® L100/N-trimethylchitosan chloride microspheres for oral insulin delivery.
abstract: Effective oral delivery of protein and peptide drugs remains an active topic in scientific research. In this study, matrix type microspheres were prepared with Eudragit® L100 containing N-trimethylchitosan chloride to improve the permeation of insulin across the intestinal epithelium via the paracellular pathway. Insulin loaded microspheres were initially formulated in accordance with a factorial design (23) and manufactured by means of a single water-in-oil emulsification/evaporation method. Based on external and internal morphology two microsphere formulations were selected from the initial formulations for further investigation in terms of particle size, dissolution behaviour and in vitro insulin transport across excised rat intestinal tissue. The initial eight microsphere formulations exhibited drug loading capacities ranging from 27.9-52.4% with different shapes and internal structures. The two selected microsphere formulations had average particle sizes of 157.3 ± 31.74 µm and 135.7 ± 41.05 µm, respectively, and mean dissolution time values for insulin release of 34.47 and 42.63 min, respectively. In vitro transport of insulin across excised rat intestinal tissue from the two selected microsphere formulations was 10.67-fold and 9.68-fold higher than the control group (insulin alone). The microsphere delivery system prepared from Eudragit® L100 containing N-trimethylchitosan chloride is therefore a promising candidate for effective oral insulin delivery.
authors.affiliation: Department of Pharmaceutics, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa.
authors.forename: Etienne
authors.initials: E
authors.lastname: Marais
authors.forename: Josias
authors.initials: J
authors.lastname: Hamman
authors.forename: Lissinda du
authors.initials: Ld
authors.lastname: Plessis
authors.forename: Righard
authors.initials: R
authors.lastname: Lemmer
authors.forename: Jan
authors.initials: J
authors.lastname: Steenekamp
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008863:Microspheres; D010316:Particle Size; D010539:Permeability; D011109:Polymethacrylic Acids / Q000737:chemistry*; D051381:Rats
chemical_list: D004337:Drug Carriers; D007328:Insulin; C118071:N-trimethyl chitosan chloride; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D048271:Chitosan