Design a Novel Transdermal Delivery System of Insulin Based on Nano-Particles Dispersed into Adhesive Gel

Abstract

Insulin is a protein hormone and is difficult to be delivered by oral route due to the enzyme activities. Ttransdermal delivery system is an alternative approach for insulin delivery by overcoming skin barrier. The objective of this project was to produce insulinloaded solid lipid nanoparticles (SLNs) hydrogels for transdermal drug delivery. SLNs containing insulin (Ins-SLNs) were produced by using reverse micelle-double emulsion technique. A serial of formulations were screened to select the optimal Ins-SLNs. These formulations involved the investigation of different types of lipids (stearic acid and compritol ATO 888), surfactants (Tween 80 and sodium cholate) and co-surfactant Poloxamer 188 varying in concentration. Particle size, zeta potential and insulin entrapment efficiency (EE) were measured as the parameters to assess the obtained Ins- SLN from each formulation. The Results showed that Ins-SLNs obtained from two types of formulations (SLN-6 and SLN-18) had the smallest particle size and the highest EE and were selected. The formulation of SLN-6 was stearic acid:Tween 80 (w:w, 20:1) with 0.1% of Poloxamer 188, from which the Ins-SLN had a particle size of ~ 87 nm and an EE % of ~ 98 %. The Ins-SLN obtained from SLN-18 (compritol ATO 888 and sodium cholate at a weight ratio of 40:1, with 0.1% of Poloxamer 188) had a particle size of ~ 100 nm and an EE % of ~ 80 %. A variety of hydrogels were made from carbopol, chitosan and carbopo-poloxamer varying in concentrations and they acted as a vehicle for the transdermal delivery of Ins- SLNs. The rheological and mechanical (hardness, compressibility, adhesiveness and cohesiveness) properties of the hydrogels were measured to select the optimal hydrogels. Result showed that two types of hydrogels, made from 3% carbopol, and 2% chitosan hydrogel with glycerol-water (1:1) respectively, had a higher adhesiveness (~ 6.3 and 12 Nmm, respectively) and the higher degree of thinxtrophy (~ 0.7 and 0.6, respectively). The selected Ins-SLNs and Ins-SLN-hydrogels were carried out for in-vitro skin permeation study. Ins-SLN showed a good permeabitility with the values of apparatus partition coefficients of 0.111 and 0.037 for SLN-6 and SLN-18, respectively. However, hardly any of the insulin loaded SLNs hydrogels occurred to permeate through the tested skin. Further study is required to seeking for more suitable hydrogels for transdermal delivery system.