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Novel PLGA-based nanoparticles for the oral delivery of insulin.

Malathi S, Nandhakumar P, Pandiyan V, Webster TJ, Balasubramanian S - Int J Nanomedicine (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Inorganic Chemistry, Guindy Campus, University of Madras, Chennai, Tamil Nadu, India.

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.

No MeSH data available.


Related in: MedlinePlus

Schematic illustration of insulin release from insulin-loaded TPGS-emulsified PEG-capped PLGA nanoparticles.Abbreviations: PEG, poly(ethylene glycol); PLGA, poly(lactic-co-glycolic) acid; TPGS, tocopherol poly(ethylene glycol) 1000 succinate.
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f5-ijn-10-2207: Schematic illustration of insulin release from insulin-loaded TPGS-emulsified PEG-capped PLGA nanoparticles.Abbreviations: PEG, poly(ethylene glycol); PLGA, poly(lactic-co-glycolic) acid; TPGS, tocopherol poly(ethylene glycol) 1000 succinate.

Mentions: The hypoglycemic effect of orally delivered insulin-loaded polymeric NPs (ISTPPLG NPs) was evaluated at 20 IU/kg dose in diabetic rats. The schematic representation of insulin released from the ISTPPLG NPs at different time intervals is shown in Figure 5. Blood glucose and serum insulin levels were compared to those of orally delivered free form of insulin at the same dose in diabetic rats. The changes observed in the blood glucose level versus time profiles are reproduced in Figure 6A. The blood glucose level was suppressed during the oral administration of ISTPPLG NPs when compared to that of diabetic control. The free insulin maintains the glucose level up to 3 hours and increases rapidly and then returns to the original level. More interestingly, the blood glucose concentration undergoes a maximum decrease at the 24th hour (P<0.05) for ISTPPLG6 NPs and at the 6th hour (P<0.05) for ISTPPLG4 NPs. Following this, the blood glucose concentration increases rapidly and returns to the original level after 12th and 24th hours, respectively, for ISTPPLG4 and ISTPPLG6 NPs. The results indicate that insulin absorption through the intestinal membrane was enhanced by the encapsulation of insulin in TPPLG NPs. The decrease in glucose levels was significantly higher in diabetic rats that received insulin-encapsulated NPs than in rats that received free insulin. The absorption of insulin was investigated by measuring the serum insulin concentration. The changes in serum insulin level with respect to time in the diabetic rats are shown in Figure 6B. The serum insulin concentration increases dramatically after the administration of ISTPPLG NPs. The ISTPPLG6 NPs-administered rats exhibit a maximum insulin value close to 6 μIU/dL within 12 hours (tmax), which is significantly higher when compared to that of other groups. However, ISTPPLG4 NPs-administered rats show a maximum insulin value close to 5 μIU/dL within 6 hours (tmax), which is significantly higher than that of the free insulin group.


Novel PLGA-based nanoparticles for the oral delivery of insulin.

Malathi S, Nandhakumar P, Pandiyan V, Webster TJ, Balasubramanian S - Int J Nanomedicine (2015)

Schematic illustration of insulin release from insulin-loaded TPGS-emulsified PEG-capped PLGA nanoparticles.Abbreviations: PEG, poly(ethylene glycol); PLGA, poly(lactic-co-glycolic) acid; TPGS, tocopherol poly(ethylene glycol) 1000 succinate.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383223&req=5

f5-ijn-10-2207: Schematic illustration of insulin release from insulin-loaded TPGS-emulsified PEG-capped PLGA nanoparticles.Abbreviations: PEG, poly(ethylene glycol); PLGA, poly(lactic-co-glycolic) acid; TPGS, tocopherol poly(ethylene glycol) 1000 succinate.
Mentions: The hypoglycemic effect of orally delivered insulin-loaded polymeric NPs (ISTPPLG NPs) was evaluated at 20 IU/kg dose in diabetic rats. The schematic representation of insulin released from the ISTPPLG NPs at different time intervals is shown in Figure 5. Blood glucose and serum insulin levels were compared to those of orally delivered free form of insulin at the same dose in diabetic rats. The changes observed in the blood glucose level versus time profiles are reproduced in Figure 6A. The blood glucose level was suppressed during the oral administration of ISTPPLG NPs when compared to that of diabetic control. The free insulin maintains the glucose level up to 3 hours and increases rapidly and then returns to the original level. More interestingly, the blood glucose concentration undergoes a maximum decrease at the 24th hour (P<0.05) for ISTPPLG6 NPs and at the 6th hour (P<0.05) for ISTPPLG4 NPs. Following this, the blood glucose concentration increases rapidly and returns to the original level after 12th and 24th hours, respectively, for ISTPPLG4 and ISTPPLG6 NPs. The results indicate that insulin absorption through the intestinal membrane was enhanced by the encapsulation of insulin in TPPLG NPs. The decrease in glucose levels was significantly higher in diabetic rats that received insulin-encapsulated NPs than in rats that received free insulin. The absorption of insulin was investigated by measuring the serum insulin concentration. The changes in serum insulin level with respect to time in the diabetic rats are shown in Figure 6B. The serum insulin concentration increases dramatically after the administration of ISTPPLG NPs. The ISTPPLG6 NPs-administered rats exhibit a maximum insulin value close to 6 μIU/dL within 12 hours (tmax), which is significantly higher when compared to that of other groups. However, ISTPPLG4 NPs-administered rats show a maximum insulin value close to 5 μIU/dL within 6 hours (tmax), which is significantly higher than that of the free insulin group.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Inorganic Chemistry, Guindy Campus, University of Madras, Chennai, Tamil Nadu, India.

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.

No MeSH data available.


Related in: MedlinePlus