Limits...
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

Synthesis of 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
getmorefigures.php?uid=PMC4383223&req=5

f1-ijn-10-2207: Synthesis of 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: About 100 mg of PLGA copolymer (PLG4:PLGA 80/20) and 50 mg of TPGS (Sigma, Bangalore, India) were dissolved in 5 mL of acetone (Fischer Scientific). The solution was sonicated for 60 seconds using a probe sonicator (Hielscher sonicator, ultrasonic processor UP 100H, Berlin, Germany [100 W, 30 kHz, 0.8 cycle, 80% amplitude]), and it was stirred continuously at 4°C. To this, 2 mL of Huminsulin (100 IU/mL, Eli-Lilly, Haryana, India) was added while stirring the solution and it was further sonicated for 60 seconds. The solution was kept in an ice bath and it formed a water-in-oil (W/O) emulsion. It was again sonicated for 180 seconds with 10 mL of aqueous PEG 2000 (PEG 2K; 1% w/v, Sigma, India) solution to form a double emulsion (W/O/W), and it was stirred continuously for 6 hours to remove the organic solvent. Then, it was centrifuged (Remi high-speed centrifuge C-24, Remi House, Mumbai, India) at 12,000 rpm (4°C) for 15 minutes and the ISTPPLG4 NPs were formed (Figure 1). The residue was freeze-dried (Christ Alpha 2–4 LSC freeze dryer, Martin Christ Gefriertocknungsanlagen GmbH, Osterode am Harz, Germany) for 12 hours, and the pellet obtained was stored at 4°C for further studies. The same protocol was also followed for the synthesis of copolymer PLG6 (PLGA 70/30).


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

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

Synthesis of 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

f1-ijn-10-2207: Synthesis of 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: About 100 mg of PLGA copolymer (PLG4:PLGA 80/20) and 50 mg of TPGS (Sigma, Bangalore, India) were dissolved in 5 mL of acetone (Fischer Scientific). The solution was sonicated for 60 seconds using a probe sonicator (Hielscher sonicator, ultrasonic processor UP 100H, Berlin, Germany [100 W, 30 kHz, 0.8 cycle, 80% amplitude]), and it was stirred continuously at 4°C. To this, 2 mL of Huminsulin (100 IU/mL, Eli-Lilly, Haryana, India) was added while stirring the solution and it was further sonicated for 60 seconds. The solution was kept in an ice bath and it formed a water-in-oil (W/O) emulsion. It was again sonicated for 180 seconds with 10 mL of aqueous PEG 2000 (PEG 2K; 1% w/v, Sigma, India) solution to form a double emulsion (W/O/W), and it was stirred continuously for 6 hours to remove the organic solvent. Then, it was centrifuged (Remi high-speed centrifuge C-24, Remi House, Mumbai, India) at 12,000 rpm (4°C) for 15 minutes and the ISTPPLG4 NPs were formed (Figure 1). The residue was freeze-dried (Christ Alpha 2–4 LSC freeze dryer, Martin Christ Gefriertocknungsanlagen GmbH, Osterode am Harz, Germany) for 12 hours, and the pellet obtained was stored at 4°C for further studies. The same protocol was also followed for the synthesis of copolymer PLG6 (PLGA 70/30).

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