Self-assembled lecithin/chitosan nanoparticles for oral insulin delivery: preparation and functional evaluation

Abstract

Purpose Here, we investigated the formation and functional properties of self-assembled lecithin/chitosan nanoparticles (L/C NPs) loaded with insulin following insulin–phospholipid complex preparation, with the aim of developing a method for oral insulin delivery. Methods Using a modified solvent-injection method, insulin-loaded L/C NPs were obtained by combining insulin–phospholipid complexes with L/C NPs. The nanoparticle size distribution was determined by dynamic light scattering, and morphologies were analyzed by cryogenic transmission electron microscopy. Fourier transform infrared spectroscopy analysis was used to disclose the molecular mechanism of prepared insulin-loaded L/C NPs. Fast ultrafiltration and a reversed-phase high-performance liquid chromatography assay were used to separate free insulin from insulin entrapped in the L/C NPs, as well as to measure the insulin-entrapment and drug-loading efficiencies. The in vitro release profile was obtained, and in vivo hypoglycemic effects were evaluated in streptozotocin-induced diabetic rats. Results Our results indicated that insulin-containing L/C NPs had a mean size of 180 nm, an insulin-entrapment efficiency of 94%, and an insulin-loading efficiency of 4.5%. Cryogenic transmission electron microscopy observations of insulin-loaded L/C NPs revealed multilamellar structures with a hollow core, encircled by several bilayers. In vitro analysis revealed that insulin release from L/C NPs depended on the L/C ratio. Insulin-loaded L/C NPs orally administered to streptozotocin-induced diabetic rats exerted a significant hypoglycemic effect. The relative pharmacological bioavailability following oral administration of L/C NPs was 6.01%. Conclusion With the aid of phospholipid-complexation techniques, some hydrophilic peptides, such as insulin, can be successfully entrapped into L/C NPs, which could improve oral bioavailability, time-dependent release, and therapeutic activity.

<p>Improving antitumor outcomes for palliative intratumoral injection therapy through lecithin&ndash;chitosan nanoparticles loading paclitaxel&ndash;cholesterol complex</p>

“…Anhydrous ethanol containing PTX-CH complex and S75 was injected in chitosan solution to prepare PTX-CH-loaded LCS_NPs using the solvent-injection method reported. 34 Chitosan solution was prepared through 1 g chitosan dissolved in 100 mL 1% acetic acid water solution. Then, 4 mL anhydrous ethanol with different concentration of PTX-CH complex was injected into 46 mL distilled water that contained chitosan and polysorbate-80 at different ratios during continuous magnetic stirring to obtain PTX-CH-loaded LCS_NPs.…”

Light Control of Insulin Release and Blood Glucose Using an Injectable Photoactivated Depot

“…These matched what is reported elsewhere, specifically that a 2–3 IU/kg dose of human insulin causes an approximately 70% reduction in glucose levels in Sprague–Dawley rats when injected subcutaneously. 25−27 We have utilized a 2.36 IU/kg (14.2 nmol/kg) dose here and observe a similar result when injected intradermally.…”

Preparation of exenatide-loaded linear poly(ethylene glycol)-brush poly(L-lysine) block copolymer: potential implications on diabetic nephropathy

“…2 However, exenatide therapy is limited due to its short plasma half-life of 2.4 h and, thus, dosing is very difficult and frequent injections are required, which are inconvenient for patients and result in low compliance. 3 Considerable interest has been generated over the past few decades in the development of effective protein-delivery systems, such as hydrogels, [4][5][6][7][8][9] polymeric nanoparticles, [10][11][12][13][14][15][16] nano-or microcapsules, [17][18][19] and…”