Novel PLGA-based nanoparticles for the oral delivery of insulin

Abstract

Background Insulin is the drug therapy for patients with insulin-dependent diabetes mellitus. A number of attempts have been made in the past to overcome the problems associated with the oral delivery of insulin, but with little success. Orally administered insulin has encountered with many difficulties such as rapid degradation and poor intestinal absorption. The potential use of D-α-tocopherol poly(ethylene glycol) 1000 succinate (TPGS)-emulsified poly(ethylene glycol) (PEG)-capped poly(lactic- co -glycolic acid) (PLGA) nanoparticles (NPs) was investigated for sustained delivery of insulin (IS). Objective To investigate the efficacy of TPGS-emulsified PEG-capped PLGA NPs (TPPLG NPs) as a potential drug carrier for the oral delivery of insulin. Methods A series of biodegradable low-molecular-weight PLGA (80/20 [PLG4] and 70/30 [PLG6]) copolymers were synthesized by melt polycondensation. The commercial insulin-loaded TPGS-emulsified PEG-capped PLGA NPs (ISTPPLG NPs) were synthesized by water–oil–water emulsion solvent evaporation method. The physical and chemical properties of PLGA copolymers, particle size, zeta potential, and morphology of the NPs were examined. The in vivo studies of ISTPPLG NPs were carried out in diabetic rats by oral administration. Results The maximum encapsulation efficiency of ISTPPLG6 NPs was 78.6%±1.2%, and the mean diameter of the NPs was 180±20 nm. The serum glucose level was significantly (twofold) decreased on treatment with ISTPPLG NPs, and there was a threefold decrease with insulin-loaded PLGA (70/30) NPs when compared to that of free insulin-treated diabetic rats. The results show that the oral administration of ISTPPLG6 NPs is an effective method of reducing serum glucose level for a period of 24 hours. Histopathological studies reveal that ISTPPLG NPs could restore the damage caused by streptozotocin in the liver, kidneys, and pancreas, indicating its biocompatibility and regenerative effects. Conclusion ISTPPLG6 NPs can act as potential drug carriers for the oral delivery of insulin.

Developments in encapsulation of insulin: Is oral delivery now possible?

“…After taking PLGA (70/30) nanoparticles, blood glucose level fell at a rate of 3 times as in the case of oral insulin solution. As reported by histopathological studies, TPPLG nanoparticles could recover damages to liver, kidney and pancreas caused by streptozotocin, suggesting that nanoparticles had both biocompatibility and repair effect [90] .…”

Poly ethylene glycol (PEG)-Related controllable and sustainable antidiabetic drug delivery systems

“…The benefits of PEGylation to NPs have been systematically summarized 93 and verified by many studies 20,[31][32][33][34]36,38,39,[94][95][96] . Basically, PEG as ingredients could resolve the instability of insulin in the harsh formulation conditions, while poly (D, L-lactide-co-glycolide acid) (PLGA) is a type of polymer that has already been successfully applied in biomacromolecule delivery 69 .…”

“…Sampath Malathi and coworkers prepared a series of D-α-tocopherol PEG 1000 succinate (TPGS)-emulsified PEG-capped PLGA NPs (ISTPPLG NPs) for insulin delivery via oral administration 32 . The rat trials suggested that the ISTPPLG NPs could successfully decrease the serum glucose level and last for 24 h. Notably, the ISTPPLG NPs showed a regenerative effect of the liver, kidneys and pancreas on diabetic rats compared to normal control rats.…”

Strategies to Use Nanoparticles to Generate CD4 and CD8 Regulatory T Cells for the Treatment of SLE and Other Autoimmune Diseases

“…Orally delivered NPs have been used to treat T1D in nonobese diabetic (NOD) mice. Oral polyethylene glycol (PEG)-PLGA loaded with insulin lowered glucose in T1D rodent models (98,99). Orally delivered PLGA NPs with al-trans retinoic acid and TGF-b induced therapeutic Tregs in T1D (increased PD-1 and CTLA4 but not Foxp3) (100).…”