Development of pH-sensitive Insulin Nanoparticles using Eudragit L100-55 and Chitosan with Different Molecular Weights

Abstract

Abstract. Insulin is a polypeptide hormone and usually administered for treatment of diabetic patients subcutaneously. The aim of this study was to investigate the efficiency of enteric nanoparticles for oral delivery of insulin. Nanoparticles were formed by complex coacervation method using chitosan of various molecular weights. Nanoparticles were characterized by drug loading efficiency determination, particle size analysis, Scanning Electron Microscopy (SEM), Zeta potential and CD spectroscopy (Circular Dichrosim). The in vitro release studies were performed at pH 1.2 and 7.4. The drug loaded nanoparticles showed 3.38% of entrapment, loading efficiency of 30.56% and mean particle size of 199 nm. SEM studies showed that the nanoparticles are non-spherical. Zeta potential increased with increasing molecular weight of chitosan. The CD spectroscopy profiles indicated that the nano-encapsulation process did not significantly disrupt the internal structure of insulin; additionally, pH-sensitivity of nanoparticles was preserved and the insulin release was pH-dependent. These results suggest that the complex coacervation process using chitosan and Eudragit L100-55 polymers may provide a useful approach for entrapment of hydrophilic polypeptides without affecting their conformation.

Novel PEG-graft-PLA nanoparticles with the potential for encapsulation and controlled release of hydrophobic and hydrophilic medications in aqueous medium

“…We also found the original NP solution loaded with insulin or naproxen was stable at room temperature for at least 1 week. Many studies have used chitosan with or without other polymers, such as Eudragit L 100-55, 25 arabic gum, 26 dextran sulfate, 27 and alginate 28 to prepare NPs with encapsulated insulin owing to its positive charge, and potential mucoadhesive and membrane permeable properties. They achieved particle size of 200-750 nm, zeta potential of −5 to −15 mV, encapsulation efficiency of 40%-85%, entrapment of 3.38%, 25 and controlled release of <30 minutes 28 and 6 hours.…”

“…Many studies have used chitosan with or without other polymers, such as Eudragit L 100-55, 25 arabic gum, 26 dextran sulfate, 27 and alginate 28 to prepare NPs with encapsulated insulin owing to its positive charge, and potential mucoadhesive and membrane permeable properties. They achieved particle size of 200-750 nm, zeta potential of −5 to −15 mV, encapsulation efficiency of 40%-85%, entrapment of 3.38%, 25 and controlled release of <30 minutes 28 and 6 hours. 27 A crosslinked dextran, 29 insulin-sodium oleate complex-loaded poly(lactide-co-glycolide), 30 and polyelectrolyte 31 NPs got an encapsulation efficiency of 45%-91.2%, particle size of 100-250 nm, and controlled release with 75%-95% entrapped insulin within 48 hours 29 and 6 hours.…”

pH-Responsive carriers for oral drug delivery: challenges and opportunities of current platforms

“…Insulin (Li et al, 2006(Li et al, , 2007Jelvehgari et al, 2010;Chen et al, 2016), DNA (Momenzadeh et al, 2015), Psoralidin (Yin et al, 2016), Fluconazole (Rencber et al, 2016) On the other hand, it is not an absolute requirement for cross-linker and homogenizer as the NPs can be prepared from two oppositely charged polymers, which provides a mild procedure to prevent drug (e.g. protein) denaturation (Jelvehgari et al, 2010), and improves oral absorption, especially the absorption at specific region, such as the colon. Recently, layer by layer (LBL) coated NPs have attracted considerable attention, which are composed of oppositely charged polyelectrolyte (like chitosan, alginate, polyacrylic acid, polyallylamine HCl, etc.)…”

Oral Delivery of Insulin: Novel Approaches

“…The nanoparticles were formed by a complex coacervation method using EudragitL100-55 and chitosan of various molecular weights. Insulin release from these nanoparticles was pH-dependent [45]. The distribution, transition and bioadhesion of insulin-loaded pH-sensitive nanoparticles prepared from EudragitL100-55 and chitosan were investigated.…”