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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

Particle size analysis of (A) ISTPPLG4 NPs and (B) ISTPPLG6 NPs.Abbreviations: ISTPPLG4 NPs, insulin-loaded tocopherol poly(ethylene glycol) 1000 succinate-emulsified poly(ethylene glycol)-capped poly(lactic-co-glycolic acid) (78/22) nanoparticles; ISTPPLG6 NPs, insulin-loaded tocopherol poly(ethylene glycol) 1000 succinate-emulsified poly(ethylene glycol)-capped poly(lactic-co-glycolic acid) (68/32) nanoparticles.
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f2-ijn-10-2207: Particle size analysis of (A) ISTPPLG4 NPs and (B) ISTPPLG6 NPs.Abbreviations: ISTPPLG4 NPs, insulin-loaded tocopherol poly(ethylene glycol) 1000 succinate-emulsified poly(ethylene glycol)-capped poly(lactic-co-glycolic acid) (78/22) nanoparticles; ISTPPLG6 NPs, insulin-loaded tocopherol poly(ethylene glycol) 1000 succinate-emulsified poly(ethylene glycol)-capped poly(lactic-co-glycolic acid) (68/32) nanoparticles.

Mentions: The mean diameter of ISTPPLG4 NPs and ISTPPLG6 NPs was found to be 180 and 120 nm, respectively, by the dynamic light scattering (DLS) method (Table 1). The ISTPPLG4 NPs exhibit a larger average diameter when compared to that of ISTPPLG6 NPs (Figure 2). The zeta potential of ISTPPLG4 NPs is -2.90 mV, whereas that of ISTPPLG6 NPs is −6.59 mV. TEM photomicrographs (Figure 3) show that ISTPPLG NPs have a smooth spherical surface and relatively uniform size distribution. The size of the NPs is below 200 nm, which is further confirmed by particle size analysis. The loading efficiency of ISTPPLG4 and ISTPPLG6 NPs is 62.3%±1.1% and 78.6%±1.2%, respectively.


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

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

Particle size analysis of (A) ISTPPLG4 NPs and (B) ISTPPLG6 NPs.Abbreviations: ISTPPLG4 NPs, insulin-loaded tocopherol poly(ethylene glycol) 1000 succinate-emulsified poly(ethylene glycol)-capped poly(lactic-co-glycolic acid) (78/22) nanoparticles; ISTPPLG6 NPs, insulin-loaded tocopherol poly(ethylene glycol) 1000 succinate-emulsified poly(ethylene glycol)-capped poly(lactic-co-glycolic acid) (68/32) nanoparticles.
© Copyright Policy
Related In: Results  -  Collection

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

f2-ijn-10-2207: Particle size analysis of (A) ISTPPLG4 NPs and (B) ISTPPLG6 NPs.Abbreviations: ISTPPLG4 NPs, insulin-loaded tocopherol poly(ethylene glycol) 1000 succinate-emulsified poly(ethylene glycol)-capped poly(lactic-co-glycolic acid) (78/22) nanoparticles; ISTPPLG6 NPs, insulin-loaded tocopherol poly(ethylene glycol) 1000 succinate-emulsified poly(ethylene glycol)-capped poly(lactic-co-glycolic acid) (68/32) nanoparticles.
Mentions: The mean diameter of ISTPPLG4 NPs and ISTPPLG6 NPs was found to be 180 and 120 nm, respectively, by the dynamic light scattering (DLS) method (Table 1). The ISTPPLG4 NPs exhibit a larger average diameter when compared to that of ISTPPLG6 NPs (Figure 2). The zeta potential of ISTPPLG4 NPs is -2.90 mV, whereas that of ISTPPLG6 NPs is −6.59 mV. TEM photomicrographs (Figure 3) show that ISTPPLG NPs have a smooth spherical surface and relatively uniform size distribution. The size of the NPs is below 200 nm, which is further confirmed by particle size analysis. The loading efficiency of ISTPPLG4 and ISTPPLG6 NPs is 62.3%±1.1% and 78.6%±1.2%, respectively.

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