Insulin-S.O (sodium oleate) complex-loaded PLGA nanoparticles: Formulation, characterization andin vivoevaluation

Abstract

S.O (sodium oleate) is an anionic surfactant, which is able to forman ionic complex with positively charged insulin at suitable pH. In a previous study, the insulin-S.O (Ins-S.O) complex was prepared by a hydrophobic ion pairing (HIP) method to improve the apparent liposolubility of insulin. The formation of the complex was further confirmed by Zeta potential and X-ray method. Based on the preliminary study, poly(lactide-co-glycolide) (PLGA) nanoparticles harbouring Ins-S.O complex was prepared via an emulsion solvent diffusion method. The effects of key parameters such as concentration of PVA, concentration of PLGA and initial-loaded drug on the properties of the nanoparticles were investigated. The insulin encapsulation efficiency (EE(%)) reached up to 91.2% and mean diameter of the nanoparticles was sized approximately 160 nm under optimal conditions. The pharmacological effects of the nanoparticles made of PLGA (75/25, Av Mw 15,000) were further evaluated to confirm their potential suitability for oral delivery. In order to evaluate hyperglycaemic effect of the nanoparticles for oral administration, Ins-S.O complex-loaded PLGA nanoparticles (20 IU/Kg) were administered orally by force-feeding to diabetic rats. In the case of the nanoparticles, the plasma glucose level reduced to 23.85% from the initial one 12 h post-administration and this continued for 24 h. The results showed that the use of Ins-S.O complex-loaded PLGA nanoparticles is an effective method of reducing plasma glucose levels. The insulin nanoparticles also improved the glycaemic response to an oral glucose challenge.

pH-sensitive poly(lactide-co-glycolide) nanoparticle composite microcapsules for oral delivery of insulin

“…16 Briefly, 1.4 mL of S.O (1 mg/mL) solution was slowly added into 4 mL of 1.0 mg/mL insulin solution in a dropwise manner under magnetic stirring. Then the cloudy mixture was centrifuged at 14,000 rpm for 15 minutes to get the complex.…”

“…A serious problem of burst release occurred when Ins-S.O-Comp was encapsulated into PLGA NPs, and this led to the low bioavailability of insulin. 16 In order to suppress the burst release of insulin from NPs and control the release of insulin in the GI tract, a novel formulation strategy was adopted where the Ins-S.O-Comp PLGA NPs were encapsulated into the enteric material Eudragit ® FS 30D using the organic spray-drying method to prepare Ins-S.O-Comp PLGA NP composite microcapsules. Eudragit ® FS 30D is insoluble in acidic media but can be dissolved by salt formation above pH 7.0, 19 so the release of insulin from the composite microcapsules can be controlled by both the PLGA NPs and the microcapsules.…”

“…16 This technique is simply performed by the interaction between ionic protein and the opposite ionic head group of fatty acid, surface-active agents, or other amphiphilic molecules at suitable pH. 17,18 Sodium oleate (S.O) was chosen as the counterpart of insulin to prepare insulin-S.O complex (Ins-S.O-Comp).…”

Structural Modification of Proteins and Peptides

“…Dai et al, Koul et al, Sun et al prepared insulin hydrophobic ion paired complex using different anionic surfactants like sodium lauryl sulphate, surfoplex, sodium deoxycholate and sodium oleate respectively in 1: 6 ratio (drug : surfactant). [49][50][51][52] The hydrophobic ion paired complex so formed has new properties like increase solubility and partitioning in 1-octanol, retained complex tertiary and secondary structures of insulin. In-vivo activity of insulin is similar to free insulin.…”

Oral Delivery of Insulin: Novel Approaches

“…Insulin encapsulation efficiency reached up to 90%. [32,33]. Mucoadhesive PLGA nanoparticles were prepared to enhance the oral bioavailability of the negatively charged PLGA nanoparticles.…”