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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 representation of the transport of drug-loaded polymeric nanoparticles (ISTPPLG NPs) across the intestinal epithelium.Abbreviations: B cell, B lymphocyte; ISTPPLG NPs, insulin-loaded tocopherol poly(ethylene glycol) 1000 succinate-emulsified poly(ethylene glycol)-capped poly(lactic-co-glycolic acid) nanoparticles; M cell, microfold cells; T cell, T lymphocyte.
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f8-ijn-10-2207: Schematic representation of the transport of drug-loaded polymeric nanoparticles (ISTPPLG NPs) across the intestinal epithelium.Abbreviations: B cell, B lymphocyte; ISTPPLG NPs, insulin-loaded tocopherol poly(ethylene glycol) 1000 succinate-emulsified poly(ethylene glycol)-capped poly(lactic-co-glycolic acid) nanoparticles; M cell, microfold cells; T cell, T lymphocyte.

Mentions: The absorption of orally administered ISTPPLG NPs depends on the successful passage of the NPs through several barriers to drug delivery. The NPs can pass either between or through the cells, depending on their physicochemical properties. The mechanisms proposed for the transport of NPs through the intestinal epithelium are 1) paracellular transport, 2) passive transcytosis or receptor-mediated transcytosis, 3) transport via M cells of Peyer’s patches, and 4) endocytosis by enterocytes.47 The larger-sized polymeric NPs (>5 nm) may not pass through the tight junction. In order to overcome this problem, enhancers such as PEG and TPGS which reversibly open the tight junction are incorporated in the insulin-encapsulated PLGA. The larger-sized particles can also undergo degradation, resulting in the release of insulin while they pass through transcellular as well as paracellular pathways (Figure 8).


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 representation of the transport of drug-loaded polymeric nanoparticles (ISTPPLG NPs) across the intestinal epithelium.Abbreviations: B cell, B lymphocyte; ISTPPLG NPs, insulin-loaded tocopherol poly(ethylene glycol) 1000 succinate-emulsified poly(ethylene glycol)-capped poly(lactic-co-glycolic acid) nanoparticles; M cell, microfold cells; T cell, T lymphocyte.
© Copyright Policy
Related In: Results  -  Collection

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

f8-ijn-10-2207: Schematic representation of the transport of drug-loaded polymeric nanoparticles (ISTPPLG NPs) across the intestinal epithelium.Abbreviations: B cell, B lymphocyte; ISTPPLG NPs, insulin-loaded tocopherol poly(ethylene glycol) 1000 succinate-emulsified poly(ethylene glycol)-capped poly(lactic-co-glycolic acid) nanoparticles; M cell, microfold cells; T cell, T lymphocyte.
Mentions: The absorption of orally administered ISTPPLG NPs depends on the successful passage of the NPs through several barriers to drug delivery. The NPs can pass either between or through the cells, depending on their physicochemical properties. The mechanisms proposed for the transport of NPs through the intestinal epithelium are 1) paracellular transport, 2) passive transcytosis or receptor-mediated transcytosis, 3) transport via M cells of Peyer’s patches, and 4) endocytosis by enterocytes.47 The larger-sized polymeric NPs (>5 nm) may not pass through the tight junction. In order to overcome this problem, enhancers such as PEG and TPGS which reversibly open the tight junction are incorporated in the insulin-encapsulated PLGA. The larger-sized particles can also undergo degradation, resulting in the release of insulin while they pass through transcellular as well as paracellular pathways (Figure 8).

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