Novel PLGA-based nanoparticles for the oral delivery of insulin

Sampath Malathi,1 Perumal Nandhakumar,2 Velayudham Pandiyan,2 Thomas J Webster,3 Sengottuvelan Balasubramanian1 1Department of Inorganic Chemistry, Guindy Campus, University of Madras, Chennai, Tamil Nadu, India; 2Department of Veterinary Biochemistry, Madras Veterinary College, Chennai, Tamil Nad...

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Autores principales:	Malathi S, Nandhakumar P, Pandiyan V, Webster TJ, Balasubramanian S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/608c3934ca9f43019ad91145787b4d1b
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spelling	oai:doaj.org-article:608c3934ca9f43019ad91145787b4d1b2021-12-02T03:55:31ZNovel PLGA-based nanoparticles for the oral delivery of insulin1178-2013https://doaj.org/article/608c3934ca9f43019ad91145787b4d1b2015-03-01T00:00:00Zhttp://www.dovepress.com/novel-plga-based-nanoparticles-for-the-oral-delivery-of-insulin-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Sampath Malathi,1 Perumal Nandhakumar,2 Velayudham Pandiyan,2 Thomas J Webster,3 Sengottuvelan Balasubramanian1 1Department of Inorganic Chemistry, Guindy Campus, University of Madras, Chennai, Tamil Nadu, India; 2Department of Veterinary Biochemistry, Madras Veterinary College, Chennai, Tamil Nadu, India; 3Department of Chemical Engineering, Northeastern University, Boston, USA 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. Keywords: drug delivery, polymer nanoparticles, poly(ethylene glycol), tocopherol poly(ethylene glycol) 1000 succinate, hypoglycemic effect, histopathologyMalathi SNandhakumar PPandiyan VWebster TJBalasubramanian SDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 2207-2218 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Malathi S Nandhakumar P Pandiyan V Webster TJ Balasubramanian S Novel PLGA-based nanoparticles for the oral delivery of insulin
description	Sampath Malathi,1 Perumal Nandhakumar,2 Velayudham Pandiyan,2 Thomas J Webster,3 Sengottuvelan Balasubramanian1 1Department of Inorganic Chemistry, Guindy Campus, University of Madras, Chennai, Tamil Nadu, India; 2Department of Veterinary Biochemistry, Madras Veterinary College, Chennai, Tamil Nadu, India; 3Department of Chemical Engineering, Northeastern University, Boston, USA 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. Keywords: drug delivery, polymer nanoparticles, poly(ethylene glycol), tocopherol poly(ethylene glycol) 1000 succinate, hypoglycemic effect, histopathology
format	article
author	Malathi S Nandhakumar P Pandiyan V Webster TJ Balasubramanian S
author_facet	Malathi S Nandhakumar P Pandiyan V Webster TJ Balasubramanian S
author_sort	Malathi S
title	Novel PLGA-based nanoparticles for the oral delivery of insulin
title_short	Novel PLGA-based nanoparticles for the oral delivery of insulin
title_full	Novel PLGA-based nanoparticles for the oral delivery of insulin
title_fullStr	Novel PLGA-based nanoparticles for the oral delivery of insulin
title_full_unstemmed	Novel PLGA-based nanoparticles for the oral delivery of insulin
title_sort	novel plga-based nanoparticles for the oral delivery of insulin
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/608c3934ca9f43019ad91145787b4d1b
work_keys_str_mv	AT malathis novelplgabasednanoparticlesfortheoraldeliveryofinsulin AT nandhakumarp novelplgabasednanoparticlesfortheoraldeliveryofinsulin AT pandiyanv novelplgabasednanoparticlesfortheoraldeliveryofinsulin AT webstertj novelplgabasednanoparticlesfortheoraldeliveryofinsulin AT balasubramanians novelplgabasednanoparticlesfortheoraldeliveryofinsulin
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Novel PLGA-based nanoparticles for the oral delivery of insulin

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